Liverpool HIV Interactions

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Abacavir (ABC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment with abacavir is needed, dolutegravir and lamivudine are available coformulated with abacavir as a fixed dose combination (Triumeq).

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acamprosate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (exact transporter unknown, possibly OATs or OCTs). No interaction is expected with dolutegravir. There is little potential for a clinically relevant interaction with lamivudine via competition for active renal transport mechanisms given the possible limited role of OCT in acamprosate’s elimination and the therapeutic index of lamivudine and acamprosate.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acarbose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acenocoumarol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acetazolamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion and in vitro studies have shown it may competitively inhibit the renal transporters OAT1, OAT3 and OAT4. No interaction is expected with dolutegravir. A clinically relevant drug interaction is unlikely with lamivudine as it is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aciclovir (Acyclovir)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acitretin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aclidinium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aclidinium bromide is rapidly and extensively hydrolyzed (non-enzymatic and enzymatic transformation by esterases and butylrylcholineesterases) to its pharmacologically inactive metabolites with only a minor role for CYP metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Adalimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adalimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Adefovir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Dolutegravir is not expected to inhibit this renal transporter. Coadministration of adefovir dipivoxil (10 mg) and lamivudine (100 mg) did not alter the pharmacokinetic profile of either drug. However, as adefovir is nephrotoxic, renal function should be monitored.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Adrenaline (Epinephrine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

African Potato

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. Use with caution as African potato could decrease concentrations of dolutegravir. Therapeutic drug monitoring of dolutegravir is recommended. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Agomelatine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Albendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. There is little potential for an interaction via competition with lamivudine for renal elimination pathways.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Albuvirtide (ABT)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with albuvirtide would be possible from a pharmacokinetic standpoint. Dolutegravir is metabolized by UGT1A1, with some contribution from CYP3A and lamivudine is eliminated renally. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on P450 enzymes. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. No interaction is expected with dolutegravir or lamivudine.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alcohol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4, however, no interaction with dolutegravir is expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Alcuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Alcuronium is predominantly excreted unchanged via the kidneys. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is some potential for exposure of alcuronium to be increased since dolutegravir inhibits the renal transporter OCT2. There is also potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of alcuronium or lamivudine. Caution is advised as alcuronium has a narrow therapeutic window.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alendronic Acid (Alendronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alfentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes CYP3A4 metabolism, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alfuzosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. P-glycoprotein is a major determinant of aliskiren bioavailability. Dolutegravir is not expected to inhibit or induce CYP450 enzymes and does not inhibit or induce P-glycoprotein in the range of clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Allopurinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Almotriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Almotriptan is partly eliminated unchanged in the urine and partly metabolized (mainly via monoamine oxidase-A and to a lesser extent by CYP3A4, CYP2D6 and flavin monooxygenase).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aloe vera

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYPs 2C9, 3A4 and 1A2, with in vivo data suggesting that CYP1A2 plays a more prominent role. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alprazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Amantadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. There is potential for dolutegravir to increase amantadine exposure via inhibition of OCT2 but the clinical relevance of this is unknown. There is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Dolutegravir is not expected to inhibit or induce UGT or CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amikacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as amikacin is eliminated by glomerular filtration.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Amiloride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Amiloride is eliminated unchanged by the kidney and in vitro data indicate that it is a substrate of OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase amiloride exposure. Amiloride may potentially compete with lamivudine for renal elimination transport mechanisms which may lead to increased concentrations of either drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aminophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Amiodarone is metabolized by CYP3A4 and in vitro data suggest it is only a weak inhibitor of CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amisulpride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally, possibly via OCT. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with amisulpride. There is little potential for an interaction with lamivudine via competition for active renal transport mechanisms given the possible limited role of OCT in amisulpride’s elimination.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amodiaquine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Amodiaquine is mainly metabolized by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of dolutegravir and artesunate-amodiaquine had no significant effect on the AUC of amodiaquine or on the AUCs of artesunate and its metabolites. No interaction is expected with lamivudine. Standard doses of artesunate-amodiaquine can be used in patients receiving 50 mg dolutegravir once daily.

Description:

Coadministration of dolutegravir and artesunate-amodiaquine was studied in two groups of HIV-negative subjects who received standard clinical treatment doses of artesunate-amodiaquine alone for 3 days (n=13) or dolutegravir alone (50 mg once daily) for 7 days (n=12), both followed by 3 days of artesunate-amodiaquine plus dolutegravir. There were no statistically significant differences in AUCs of artesunate and it metabolites (dihydroatmesinin and desethylamodiaquine) or on the AUC of amodiaquine The authors conclude that standard doses of artesunate-amodiaquine can be used in patients receiving 50 mg dolutegravir once daily.

Dolutegravir interactions with artemether-lumefantrine and amodiaquine-artesunate. Walimbwa SI, Lamorde M, Waitt C, et al. Conference on Retroviruses and Opportunistic Infections, March 2018, Boston, Abstract 459.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amoxicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3, but dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by OCT2.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amphetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphetamine is metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ampicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion; it is reduced by probenecid. About 20 to 40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60 to 80% is excreted in the urine within 6 hours. No interaction is expected with dolutegravir. As lamivudine is eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased levels of either drug when ampicillin is administered intravenously. When administered orally, there is little potential for significant interaction.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Anastrozole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Anidulafungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. Dovato should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations, such as antacids. Simultaneous coadministration of dolutegravir (50 mg once daily) and a magnesium/aluminium containing antacid (Maalox) decreased dolutegravir Cmax, AUC and Ctrough by 72%, 74% and 74%, respectively. When antacid was administered 2 hours after dolutegravir (50 mg once daily), dolutegravir Cmax, AUC and Ctrough decreased by 18%, 26% and 30%, respectively. Coadministration with antacids containing calcium carbonate has not been studied. No interaction is expected with lamivudine.

Description:

Coadministration of a magnesium/aluminium containing antacid decreased dolutegravir AUC and Cmax by 74% and 72%, due to complex binding to polyvalent ions. Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Simultaneous coadministration of antacid (Maalox) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 72%, 74% and 74%, respectively. When antacid was administered 2 hours after dolutegravir (50 mg once daily), dolutegravir Cmax, AUC and Ctrough decreased by 18%, 26% and 30%, respectively. Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Healthy volunteers (n=16) received dolutegravir (50 mg single dose) alone, or simultaneously administered with a liquid antacid (Maalox, single dose), or administered 2 hours before an antacid. Simultaneous coadministration decreased dolutegravir AUC, Cmax and Ctrough by 74%, 72% and 74%, respectively. With staggered administration, dolutegravir AUC, Cmax and Ctrough decreased by 26%, 18% and 30%, respectively. Dolutegravir should be administered 2 hours before or 6 hours after an antacid.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Anti-thymocyte globulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thymoglobulins are cleared by the reticuloendothelial system.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Dolutegravir is mainly metabolized by UGT1A1 and is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Apomorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Argatroban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Drug-drug interactions studies performed with substrates of different cytochromes and P-glycoprotein (i.e., acetaminophen, lidocaine, warfarin, digoxin) indicate that argatroban has a low potential to cause drug-drug interactions and therefore is unlikely to alter the exposure of dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Artemisinin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolised via UGT1A9 and 2B7. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ascorbic Acid (Vitamin C) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. Lamivudine is predominantly eliminated unchanged via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected. A pharmacokinetic interaction is unlikely with dolutegravir and vitamin C itself as dolutegravir does not interfere with this metabolic pathway. However, vitamin C can be found in multivitamin preparations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Asenapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, 2D6 (minor). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Asparaginase

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Limited data suggest that asparaginase is likely to be eliminated by the reticulo endothelial system. Less than 0.1% of a total injected dose is recovered in urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aspirin [Acetylsalicylic acid] (Analgesic)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6). Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Aspirin [Acetylsalicylic acid] (Anti-platelet)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolized by CYP2D6, CYP2J2 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Atazanavir alone (ATV)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with atazanavir. Coadministration of atazanavir alone and dolutegravir increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%, respectively. No significant effect on lamivudine and zidovudine concentrations was observed when atazanavir (400 mg once daily) was coadministered with lamivudine/zidovudine (150/300 mg twice daily).

Description:

Coadministration of dolutegravir and atazanavir increased dolutegravir AUC, Cmax and Cmin by 91%, 50% and 180%, respectively, due to inhibition of UGT1A1 and CYP3A enzymes. There was no change in atazanavir or ritonavir pharmacokinetics. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (30 mg once daily) and atazanavir alone (400 mg once daily) or atazanavir/ritonavir (300/100 mg once daily) was studied in two groups of HIV-negative subjects (n=12 per group). Coadministration with atazanavir alone increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%. Coadministration with atazanavir/ritonavir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%. These combinations were well tolerated. The authors recommend no dose adjustment when dolutegravir is coadministered with atazanavir alone or atazanavir/ritonavir. Note, this study was performed with a dose of dolutegravir lower than the licensed one.

Effect of atazanavir and atazanavir/ritonavir on the pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Song I, Borland J, Chen S, et al. Br J Clin Pharmacol, 2011, 72(1):103-8.

Coadministration of atazanavir (400 mg once daily) with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) was studied in 19 subjects. There were negligible increases in the Cmax, AUC and Cmin of lamivudine (4%, 3% and 12%, respectively). Cmax and AUC of zidovudine increased by 5% and there was a 31% and 18% reduction in the Cmin of zidovudine and zidovudine glucuronide, respectively.

Steady-state pharmacokinetic interaction study of atazanavir with lamivudine and zidovudine in healthy subjects. Mummaneni V, Randall D, Geraldes M, et al. 42nd ICAAC, San Diego, September 2002, abstract H1713.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Atazanavir/cobicistat (ATV/c)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir/cobicistat would be possible from a pharmacokinetic standpoint. Atazanavir/cobicistat is expected to increase dolutegravir plasma concentrations, but dolutegravir is not expected to affect the pharmacokinetics of atazanavir/cobicistat. No interaction is expected with lamivudine. However, cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir/cobicistat should not be coadministered with lamivudine in patients with creatinine clearance less than 70 ml/min.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Atazanavir + ritonavir (ATV/r)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with atazanavir/ritonavir. Coadministration of atazanavir/ritonavir and dolutegravir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%, respectively. There was no effect on atazanavir or ritonavir. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and atazanavir/ritonavir increased dolutegravir AUC, Cmax and Cmin by 62%, 34% and 121%, respectively, due to inhibition of UGT1A1 and CYP3A enzymes. There was no change in atazanavir pharmacokinetics when compared to historical controls. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (30 mg once daily) and atazanavir alone (400 mg once daily) or atazanavir/ritonavir (300/100 mg once daily) was studied in two groups of HIV-negative subjects (n=12 per group). Coadministration with atazanavir alone increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%. Coadministration with atazanavir/ritonavir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%. These combinations were well tolerated. The authors recommend no dose adjustment when dolutegravir is coadministered with atazanavir alone or atazanavir/ritonavir. Note, this study was performed with a dose of dolutegravir lower than the licensed one.

Effect of atazanavir and atazanavir/ritonavir on the pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Song I, Borland J, Chen S, et al. Br J Clin Pharmacol, 2011, 72(1):103-8.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Atenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. There is potential for dolutegravir to increase atenolol exposure via inhibition of OCT2. Based on the drug-drug interaction study with metformin (another drug transported by OCT2 and MATE1), the increase in atenolol exposure is expected to be ~80% or ~110% when dolutegravir is administered once daily and twice daily, respectively. There is potential for competition with atenolol and lamivudine for elimination via renal transport proteins, which may lead to increased concentrations of either drug. It is recommended to start atenolol at a lower dose and adjust dosage until the desired clinical effect is achieved.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atovaquone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atovaquone is mainly eliminated unchanged in the faeces.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atropine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Avanafil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avanafil is primarily metabolized by CYP3A4 and does not inhibit or induce CYPs or UGTs. Dolutegravir is mainly metabolized by UGT1A1 and is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is metabolized to 6-mercaptopurine which is further inactivated by xanthine oxidase and thiopurine methyltransferase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. In vitro data indicate that dolutegravir does not inhibit P-glycoprotein and MRP2 at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Baclofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as baclofen is primarily eliminated by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Basiliximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Beclometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bedaquiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Concentrations are unlikely to be affected by dolutegravir or lamivudine. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Belatacept

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Benazepril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bendroflumethiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes. Similarly, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. A drug interaction with lamivudine is unlikely as lamivudine and bendroflumethiazide are eliminated by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Benserazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as benserazide is hydrolysed to trihydroxybenzylhydrazine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Benznidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Betahistine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Betamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4 and is a moderate inducer of CYP3A4. A clinically significant interaction with dolutegravir is not expected as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentration and CYP3A does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Betrixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Dolutegravir does not inhibit or induce P-gp and no interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bevacizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bexarotene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Bexarotene is mainly metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bezafibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of bezafibrate dose is eliminated unchanged in the urine and in vitro data suggest that bezafibrate inhibits the renal transporter OAT1. No interaction is expected with dolutegravir or with lamivudine as it is excreted by different renal transporters.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Bictegravir/ Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Description:

Biktarvy should not be co-administered with other antiretroviral medicinal products.

Biktarvy Summary of Product Characteristics, Gilead Sciences Ltd, June 2019.

As Biktarvy is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

Biktarvy Prescribing Information, Gilead Sciences Inc, August 2019.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Biperiden

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on limited information concerning the metabolism and clearance of biperiden, there is little potential for a clinically significant interaction. Limited human data suggest biperiden undergoes hydroxylation in the liver.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bisacodyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Lamivudine is eliminated by OCT2 and in vitro data indicate that bisoprolol inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown given the good tolerability of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Black cohosh (Actaea racemosa, Cimicifuga racemosa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on dolutegravir is expected as in vitro studies suggest black cohosh is unlikely to affect UGT1A1 at clinically relevant concentrations. No effect on lamivudine is expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bleomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase. Furthermore, ~67% of the administered drug is excreted unchanged in urine probably by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bortezomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent CYP1A2, 2D6 and 2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Bosentan could potentially decrease dolutegravir exposure although to a moderate extent as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Budesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bupivacaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is predominantly metabolized via CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Renal excretion of unchanged bupivacaine is thought to account for approximately 1% of a dose and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Buprenorphine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. Coadministration of buprenorphine and lamivudine had no significant effect on buprenorphine pharmacokinetics or NRTI concentrations when compared to control data.

Description:

Coadministration of buprenorphine (14-16 mg once daily, stable dose with naloxone) and lamivudine (300 mg once daily) was studied in 7 opioid-dependent patients and values compared to historical data. Coadministration had few effects on the pharmacokinetics of buprenorphine and its metabolites. Buprenorphine AUC, Cmax and Cmin increased by ~5%, ~1% and ~2%, respectively. Norbuprenorphine AUC, Cmax and Cmin increased by ~6%, ~3% and ~4%, respectively; buprenorphine-3-glucuronide AUC and Cmin increased by ~10% and ~28%, Cmax was unchanged; norbuprenorphine-3-glucuronide AUC, Cmax and Cmin increased by ~7%, ~12% and ~11%, respectively. Only the increases in norbuprenorphine-3-glucuronide AUC and Cmax were statistically significant. No subjects showed evidence of opiate withdrawal symptoms. Lamivudine concentrations during coadministration did not differ significantly from values observed in healthy, nonopioid-dependent, historical controls. The authors conclude that standard doses of lamivudine may be safely given with standard buprenorphine/naloxone treatment.

Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir. Baker J, Rainey P, Moody D, et al. Am J Addict, 2010, 19(1): 17-29.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bupropion (Amfebutamone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Buspirone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Caffeine citrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Calcium folinate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. No interaction is expected with lamivudine. In theory, calcium could chelate with dolutegravir and potentially decrease the amount of dolutegravir available to bind to the active site of the HIV integrase. However, given that the extent of chelation is dependent on the amount of calcium, this risk is predicted to be low when administering calcium folinate in small doses at frequent intervals. Since calcium is distributed rapidly, separating the intake of dolutegravir from the IV administration of calcium folinate by 2 hours should eliminate any risk of chelation.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Calcium supplements

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. Calcium is eliminated through faeces, urine and sweat. No interaction with lamivudine is expected. Simultaneous coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. When taken with food, Dovato and supplements containing calcium can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium.

Description:

Coadministration of calcium supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 39%, 37% and 39%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing calcium can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. When taken with food, Dovato and supplements containing calcium can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=12) decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir (n=11) had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. Dolutegravir and calcium supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Canagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Candesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as candesartan is mainly eliminated unchanged via urine and bile.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cannabidiol (CBD)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit CYP3A4, UGT1A1 or intestinal transporters in the range of doses in clinical use. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

In vitro studies show that at supra-physiological concentrations, cannabidiol (CBD) is an inhibitor of P-gp and BCRP. Observed plasma concentrations of CBD with doses used in clinical use are a couple of orders of magnitude smaller than those required for inhibition of P-gp and BCRP. Thus, substrates of these transporters are unlikely to be victims of a drug interaction with CBD. Likewise, in vitro studies showing inhibition of CYP enzymes by CBD use supra-physiological concentrations of CBD that would not be seen in vivo with oral dosing. Therefore, CBD is unlikely to be a perpetrator of drug interactions via CYP inhibition.

An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Iffland K and Grotenhermen F. Cannabis Cannabinoid Res, 2017, 2(1): 139-154.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cannabis

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Tetrahydrocannabinol (THC, the psychoactive component of cannabis), is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Capecitabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleoside analogues such as lamivudine may compete for these metabolic pathways. The clinical relevance of this interaction is unknown. No interaction is expected with dolutegravir.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Capreomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Capreomycin is predominantly excreted via the kidneys as unchanged drug, partly by glomerular filtration and possibly partly by tubular secretion (renal transporter not identified). There is some potential for exposure of capreomycin to be increased since dolutegravir inhibits the renal transporter OCT2. As capreomycin may potentially compete with lamivudine for renal elimination transport mechanisms, levels of capreomycin or lamivudine may hypothetically be raised. Renal function should be monitored as clinically appropriate.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Captopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1 (40-50% as unchanged drug, the rest as disulfide and other metabolites). No interaction is expected with dolutegravir or with lamivudine as it is eliminated by different renal transporters.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No significant interaction is expected with lamivudine. However, the dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with certain drugs (such as carbamazepine) that may decrease dolutegravir concentrations. Coadministration of carbamazepine (300 mg twice daily) and dolutegravir alone (50 mg once daily) decreased dolutegravir Cmax, AUC and Cmin by 33%, 49% and 73%, respectively. The European and US product labels for Dovato recommend that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping carbamazepine as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. Limited data from a small number of patients showed TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges and trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs.

Description:

Coadministration of dolutegravir and carbamazepine decreased dolutegravir AUC, Cmax and Cmin by 49%, 33% and 73%, respectively. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with carbamazepine. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with carbamazepine (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered certain drugs that may decrease dolutegravir concentrations. An additional dolutegravir 50-mg tablet, separated by 12 hours from Dovato, should be taken. Coadministration of carbamazepine (300 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Cmin by 33%, 49% and 73%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The drug-drug interactions between antiretrovirals and carbamazepine or oxcarbazepine were evaluated in a clinical setting using therapeutic drug monitoring (TDM) trough concentrations collected from HIV+ patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. Eleven HIV-positive patients prescribed carbamazepine (n=7) or oxcarbazepine (n=4) were identified. All the TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges. Trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs (191 ± 78 versus 1096 ± 510 ng/mL). Co-administration of carbamazepine or oxcarbazepine with dolutegravir should be avoided owing to the potential risk of virological failure; the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

Drug-drug interactions between antiretrovirals and carbamazepine/oxcarbazepine: a real-life investigation. Cattaneo D, Baldelli S, Cozzi V, et al. Ther Drug Monit. 2020;42(2):330-334.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Carbidopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbidopa is partly metabolized and partly eliminated unchanged (30% of the total urinary excretion).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Carbimazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (also known as methimazole). Despite this potential hepatic metabolism very few data exist on carbimazole drug interactions and a marked interaction is not expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Carboplatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration and there is little potential for a pharmacokinetic interaction.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Caspofungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. In vitro data indicate that caspofungin is a substrate of the hepatic transporter OATP1B1, but there is no evidence that dolutegravir inhibits OATP1B1. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cat's Claw (Uncaria tomentosa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Cat's claw is unlikely to affect dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cefalexin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged via the kidneys (by glomerular filtration and tubular secretion via OAT1 and MATE1). Dolutegravir is not expected to inhibit these renal transporters and lamivudine is eliminated by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cefazolin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cefixime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefixime is renally excreted predominantly by glomerular filtration, with no significant active renal tubular secretion. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal elimination transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cefotaxime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolized by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine (about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite). In vitro studies indicate that OATs participate to the renal elimination of cefotaxime. Dolutegravir is not expected to inhibit these renal transporters and lamivudine is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ceftazidime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftazidime is excreted predominantly by renal glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ceftriaxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Celecoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is metabolised mainly by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. No interaction is expected with dolutegravir. Lamivudine is eliminated by OCT2 and in vitro data indicate that cetirizine inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown and given the good tolerability of lamivudine, no a priori dose adjustment of lamivudine is needed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cetuximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetuximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlorambucil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorambucil is almost completely metabolized (little is known about chlorambucil metabolism in humans, most probably non CYP mediated) and has extremely low urinary excretion.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolized by glucuronidation via UGT2B7 whereas dolutegravir is mainly eliminated by glucuronidation via UGT1A1. Dolutegravir is not expected to inhibit UGTs at clinically relevant concentrations. Although, in vitro studies have shown that chloramphenicol inhibits CYP3A4 and CYP2C19, CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlordiazepoxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolized by hepatic microsomal enzymes. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chloroquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Due to the multiple elimination pathways, a clinically significant interaction with lamivudine is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlorphenamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Approximately 22% of a chlorphenamine dose is excreted unchanged in the urine and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlortalidone (Chlorthalidone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as chlortalidone is mainly excreted unchanged in the urine and faeces.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ciclesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4 mediated metabolism. Dolutegravir is not expected to interact with ciclesonide metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclosporin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cidofovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Dolutegravir is not expected to inhibit these renal transporters. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cilazapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cilazapril is mainly eliminated unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction was observed with lamivudine.

Description:

Coadministration has not been studied but a clinically significant interaction is unlikely. No dosage adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys (by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolized and partially cleared through the bile and intestine. Dolutegravir is not expected to inhibit OAT3 and lamivudine is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cisapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cisatracurium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature (Hofmann elimination).

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Cisplatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1. OCT2 facilitates the entry of cisplatin in the tubular cell whereas MATE1 facilitates its elimination in the urine. In vitro data indicate that dolutegravir is a moderate inhibitor of OCT2 but causes no clinically significant inhibition of MATE1. Inhibition of OCT2 will lead to lower concentrations of cisplatin inside the tubular cell which represents an advantage as this may reduce the risk of cisplatin related nephrotoxicity. However, cisplatin may impair renal function with may alter the elimination of lamivudine. Closely monitor creatinine clearance.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clarithromycin is a strong inhibitor of CYP3A4, but CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clavulanic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolized (likely non CYP mediated pathway) and excreted in the urine by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4 with some metabolites having antibacterial activity. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Clobazam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Clobazam is a weak inducer and could potentially decrease dolutegravir exposure although to a limited extent. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clobetasol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug interaction is unlikely with the topical use of clobetasol.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Three metabolites, two glucuronides, have been identified in urine, As glucuronidation has a minor role in clofazimine elimination, an interaction with dolutegravir via this mechanism is unlikely. An interaction with lamivudine via competition for renal elimination pathways is unlikely as renal excretion has a minor role in clofazimine elimination.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Dolutegravir is not expected to inhibit OAT1. No interaction is expected with lamivudine as it is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clomifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP2D6 is thought to have a role in clomifene metabolism and renal excretion of clomifene is thought to account for approximately 8% of an oral dose. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. There is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clomipramine (Chlorimipramine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clonazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolized by CYP3A4 and does not induce metabolizing enzymes. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). No interaction is expected with dolutegravir. Clonidine is a weak inhibitor of OCT2 and is unlikely to cause a clinically relevant interaction with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clorazepate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted via glomerular filtration and tubular secretion. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction as total renal elimination of cloxacillin represents approximately 35% of a dose. There is little potential for significant interactions with lamivudine via competition for renal transport.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cocaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cocaine is metabolized by several non CYP mediated pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Codeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is a substrate of CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Colecalciferol (Vitamin D3) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. No interaction is expected with lamivudine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with dolutegravir and vitamin D given as a single agent (i.e. not with calcium or in a multivitamin preparation) or as an injection. However, colecalciferol can be found in multivitamin preparations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cubeb pepper (Piper cubeba)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence to suggest that Piper cubeba impacts UGTs.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Cyanocobalamin (Vitamin B12) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with vitamin B12 when given as a single agent (i.e. not in a multivitamin preparation) or as an injection. However, vitamin B12 can be found in multivitamin preparations and simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. No interaction is expected with lamivudine.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cyclophosphamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cycloserine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cyproterone acetate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cytarabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytarabine is metabolized by cytidine deaminase. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is not metabolized by CYP450 isoenzymes and is mainly cleared by glomerular filtration. The prodrug of dabigatran is a substrate of P-gp and in vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. There is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dacarbazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacarbazine is activated to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Daclatasvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir (50 mg once daily) and daclatasvir (60 mg once daily) had no significant effect on daclatasvir AUC (2% decrease), Cmax (3% increase) or Cmin (6% increase). There was no clinically relevant change in dolutegravir exposure (AUC, Cmax and Cmin increased by 33%, 29% and 45%, respectively). No interaction with lamivudine is expected.

Description:

Coadministration of dolutegravir and daclatasvir increased dolutegravir AUC, Cmax and Cmin by 33%, 29% and 45%, respectively. There was no change in daclatasvir pharmacokinetics when compared to historical controls. Daclatasvir did not change dolutegravir plasma concentration to a clinically relevant extent. Dolutegravir did not change daclatasvir plasma concentration. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of daclatasvir (60 mg once daily) and dolutegravir (50 mg twice daily) increased daclatasvir Cmax and Cmin by 3% and 6%, but decreased AUC by 2%; dolutegravir Cmax, AUC and Cmin increased by 29%, 33%, and 45% respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dactinomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dactinomycin is minimally metabolized.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dapagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dapsone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapsone is mainly metabolized by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Darifenacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Darunavir/cobicistat (DRV/c)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with darunavir/cobicistat would be possible from a pharmacokinetic standpoint. Coadministration of dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. No interaction is expected with lamivudine.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) was studied in 9 healthy volunteers. Dolutegravir Cmax, AUC, and C24 decreased by 11%, 16% and 19%, respectively, when coadministered. Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively; cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. The authors conclude that the combination of dolutegravir and darunavir/cobicistat can safely be used in the treatment of HIV-1.

Elliot ER, Cerrone M, Else L, et al. Pharmacokinetics of dolutegravir with and without darunavir/cobicistat. Conference on Retroviruses and Opportunistic Infections, March 2018, Boston, Abstract 468.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Darunavir/Cobicistat/ Emtricitabine/Tenofovir alafenamide (DRV/c/FTC/TAF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir, lamivudine) and Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Description:

Symtuza should not be administered concomitantly with medicinal products containing lamivudine or tenofovir disoproxil (as fumarate, phosphate or succinate).

Symtuza Summary of Product Characteristics, Janssen-Cilag Ltd, June 2023.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Darunavir + ritonavir (DRV/r)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration of darunavir/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with darunavir/ritonavir. Coadministration of darunavir/ritonavir and dolutegravir decreased dolutegravir AUC, Cmax and Ctrough by 22%, 11% and 38%, respectively; there was no effect on darunavir or ritonavir. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and darunavir/ritonavir decreased dolutegravir AUC, Cmax and Cmin by 22%, 11% and 38%, respectively, due to induction of UGT1A1 and CYP3A enzymes. There was no change in darunavir or ritonavir pharmacokinetics. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dasatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is metabolized by CYP3A4 and inhibits this same enzyme. A clinically significant interaction is not expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Daunorubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No interaction is expected with dolutegravir. A clinical study reported that antiretroviral regimens containing lamivudine had no effect on the pharmacokinetics of liposomal daunorubicin.

Description:

A study investigated the pharmacokinetics of liposomal daunorubicin (DaunoXome) administered alone or in combination with antiviral therapy including protease inhibitors (PI) to HIV-positive patients affected by Kaposi's sarcoma (KS). Patients with extensive or rapidly progressing AIDS-related KS (n=18) received DaunoXome at a dose of 40mg/m2 alone or with triple combination therapy consisting of one PI plus two nucleoside reverse transcriptase inhibitors (stavudine, didanosine, lamivudine, or zidovudine). Daunorubicin pharmacokinetics were determined in a total of 23 cycles, 6 with DaunoXome alone, 9 in combination with indinavir, 6 with ritonavir and 2 with saquinavir. Plasma samples were obtained at different times during the 72 h after DaunoXome administration. Daunorubicin and daunorubicinol plasma levels were determined by high-performance liquid chromatography. There were no significant differences in the pharmacokinetic parameters of daunorubicin in patients receiving DaunoXome in combination with indinavir and ritonavir compared with those in patients not receiving PIs. Therefore in patients affected by AIDS-related KS treated with Highly Active AntiRetroviral Therapy (HAART) there is no pharmacokinetic justification for reducing the doses of DaunoXome.

The pharmacokinetics of liposomal encapsulated daunorubicin are not modified by HAART in patients with HIV-associated Kaposi's sarcoma. Fumagalli L, Zucchetti M, Parisi I et al. Cancer Chemother Pharmacol. 2000;45(6):495-501.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Delamanid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Dolutegravir does not affect CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Denosumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway. (Note, caution is required if denosumab is given with calcium supplements as dolutegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced dolutegravir concentrations.)

Description:

Coadministration of calcium supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 39%, 37% and 39%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing calcium can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. When taken with food, Dovato and supplements containing calcium can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=12) decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir (n=11) had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. Dolutegravir and calcium supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desflurane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desflurane is almost exclusively eliminated unchanged by the lungs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desogestrel (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desogestrel (POP)

Quality of Evidence: Very Low

Summary:

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dexmedetomidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly CYP2A Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dextropropoxyphene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolized by CYP3A. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diclofenac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9 (catalyzes the major route of diclofenac oxidative metabolism). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diethylcarbamazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diethylcarbamazine is mainly excreted unchanged in the urine. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Digoxin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as digoxin is eliminated renally via the renal transporters OATP4C1 and P-glycoprotein. In vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. Lamivudine is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dihydrocodeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dihydroergotamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydroergotamine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diloxanide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dipyridamole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Dolutegravir does not inhibit or induce these UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Disopyramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Disopyramide is metabolized by CYP3A4 (25%) whereas 50% of the drug is eliminated unchanged in the urine (possibly via OCT2). In vitro data indicate that dolutegravir inhibits OCT2 and may increase disopyramide exposure. Caution is warranted and clinical monitoring is recommended if coadministered. Data from animal studies indicate that disopyramide is a weak inhibitor of the renal transporter OCT2. Since OCT2 may contribute to the renal elimination of disopyramide, there is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Disulfiram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disulfiram is reduced to diethyldithiocarbamic acid, is conjugated with glucuronic acid, oxidised to sulphate, methylated and decomposed to diethylamine and carbon disulphide.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Docetaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Docetaxel is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Dofetilide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied and is contraindicated in the US product label for Dovato. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Dolutegravir is an inhibitor of OCT2 and therefore can increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias. There is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug.

Description:

Dovato is contraindicated in patients receiving dofetilide, due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events. Dolutegravir, a component of Dovato, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Dolutegravir is not expected to inhibit or induce UGT or CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Dolutegravir (DTG)

Quality of Evidence: Very Low

Summary:

The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. An additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), is recommended with these medications.

Description:

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir, lamivudine) and Triumeq (dolutegravir, abacavir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both Dovato and Triumeq contain dolutegravir and lamivudine and should not be taken with any other medicinal products also containing dolutegravir and lamivudine.

Description:

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Dolutegravir/Rilpivirine (DTG/RPV)

Quality of Evidence: Very Low

Summary:

Juluca (dolutegravir, rilpivirine) and Dovato (dolutegravir/lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both Juluca and Dovato contain dolutegravir and should not be taken with any other medicinal products also containing dolutegravir.

Description:

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Domperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dopamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. Renal elimination of unchanged dopamine is minimal. There is little potential for dopamine to affect the disposition of antiretrovirals, or to be affected if co-administered with antiretrovirals.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Doravirine (DOR)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with doravirine would be possible from a pharmacokinetic standpoint. Doravirine is metabolized by CYP3A4. Coadministration of dolutegravir (50 mg once daily) and doravirine (200 mg once daily) did not significantly alter doravirine exposure. Dolutegravir AUC, Cmax and Cmin were increased by 36%, 43% and 27%, respectively (n=11). These changes are not considered as clinically significant No interaction is expected with lamivudine.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) with doravirine (200 mg once daily) was studied in 11 healthy subjects. Dolutegravir AUC, C24 and Cmax were increased by 36%, 27% and 43%, respectively. Doravirine AUC was unchanged, while C24 decreased by 2% and Cmin increased by 6%. The authors conclude that these changes are not clinically relevant, and are well within safety margins.

A two-way steady-state pharmacokinetic interaction study of doravirine (MK-1439) and dolutegravir. Anderson MS, Khalilieh S, Yee KL, et al. Clin Pharmacokinet, 2017, 56(6): 661-669.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Doravirine/Lamivudine/ Tenofovir-DF (DOR/3TC/TDF)

Quality of Evidence: Very Low

Summary:

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Dovato (dolutegravir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both Delstrigo and Dovato contain lamivudine and should not be taken with any other medicinal products also containing lamivudine.

Description:

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Doxazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Doxorubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Doxycycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No significant metabolism of doxycycline occurs and it is cleared intact by renal and biliary mechanisms. No interaction is expected with dolutegravir and there is little potential for a clinically significant interaction with lamivudine via competition for renal elimination transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Droloxifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Dolutegravir is not expected to induce or inhibit UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dronabinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Drospirenone (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir does not interact with these metabolic pathways and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Drospirenone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dulaglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Duloxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dutasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dydrogesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Echinacea

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Echinacea has a selective effect on CYP3A4 activity (inhibition of intestinal CYP3A4 and induction of hepatic CYP3A4) and its effect on the net exposure of a CYP3A4 substrate will depend on the extraction of the drug at the intestinal and hepatic sites. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ecstasy (MDMA)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is eliminated primarily as unchanged drug in urine. Edoxaban is minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%). Edoxaban is a substrate for P-gp but dolutegravir does not inhibit or induce P-gp. There is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Efavirenz (EFV)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with efavirenz would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration with efavirenz. Coadministration of dolutegravir and efavirenz decreased dolutegravir AUC, Cmax and Cmin by 57%, 39% and 75%, respectively. There was no change in efavirenz when compared to historical controls. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after Dovato) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Description:

Coadministration of dolutegravir and efavirenz decreased dolutegravir AUC, Cmax and Cmin by 57%, 39% and 75%, respectively, due to induction of UGT1A1 and CYP3A enzymes. There was no change in efavirenz when compared to historical controls. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with efavirenz. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the efavirenz co-administration (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) and efavirenz (600 mg once daily) was studied in 12 HIV-negative subjects. In the presence of efavirenz, dolutegravir AUC, Cmax and Ctrough decreased by 57%, 39%, 75%, respectively (likely via UGT and CYP3A induction by efavirenz). However, dolutegravir concentrations remained 4-5 fold higher than the protein-adjusted IC90 for the wild type virus and the authors concluded no dose adjustment was required when dolutegravir and efavirenz were given concomitantly in integrase naïve patients.

Song I, Borland J, Lou Y et al. 12th International Workshop on Clinical Pharmacology of HIV Therapy, Miami 2011; abstract O_02.

Efavirenz is primarily metabolized by CYP2B6. This study evaluated the effect of CYP2B6 genotype on the pharmacokinetic interaction between efavirenz and dolutegravir. Twelve HIV-negative adults received dolutegravir 50 mg once daily for 5 days (period 1), followed by efavirenz 600 mg + dolutegravir 50 mg once daily for 14 days (period 2). Nine individuals were genotyped for rs3745274 (1/*1, *1/*6 or *6/*6). Dolutegravir Ctrough decreased by 85% in CYP2B6 slow and intermediate metabolizers and by 60% in CYP2B6 normal metabolizers. Efavirenz half-life was 2.7 times higher in CYP2B6 slow (39.1 hours, 95% CI 17.1-89.5 hours) than in normal metabolizers (14.3 hours, 95% CI 12.6-16.1 hours) and was 24.6 hours in the intermediate metabolizers. This study demonstrated a strong association between CYP2B6 slow metabolizer genotype (and resulting increased efavirenz exposure) with plasma dolutegravir concentrations. Switch from efavirenz to dolutegravir is of little concern for individuals with viremia well controlled because at no time both dolutegravir and efavirenz concentrations simultaneously fall below their respective clinical target concentrations. However, switch could be problematic in individuals with uncontrolled viremia and efavirenz resistances in which case efavirenz will not protect dolutegravir during its period of subtherapeutic exposure. The safest strategy would be to switch from efavirenz to dolutegravir when HIV is well suppressed. If HIV replication is not controlled and if resistances to efavirenz are present, prescription of dolutegravir 50 mg twice daily might be considered up to 2 weeks after the switch. The same strategy might be applied to CYP2B6 slow metabolizers.

Implications of efavirenz pharmacogenetics when switching from efavirenz- to dolutegravir-containing antiretroviral regimens. Haas DW, Acosta EP. Clin Infect Dis. 2021; 72(10):1820-1822.

Dolutegravir is the preferred second-line antiretroviral backbone agent for people living with HIV failing a first-line efavirenz-based regimen. Efavirenz induces metabolism and was shown to reduce dolutegravir exposure for up to 14 days when switching from an efavirenz-based regimen. Exposure to sub-therapeutic dolutegravir concentrations in people living with HIV failing efavirenz-based first-line antiretrovirals could select for dolutegravir resistance mutations. This study evaluated dolutegravir trough concentrations after switching from a failing first-line efavirenz-based regimen to assess the need for a lead-in supplemental dose of dolutegravir. Participants failing a first-line efavirenz-based regimen were randomized to receive supplemental dolutegravir 50 mg or placebo for 14 days post-switch to tenofovir/lamivudine/dolutegravir (TLD). Efavirenz was measured at baseline and days 3, 7 and 14 and dolutegravir trough concentrations at days 3, 7, 14 and 28. 36 participants were enrolled: 11 in the placebo arm and 25 in the supplemental arm. One participant in the supplemental dolutegravir arm and none in the placebo arm had a dolutegravir trough concentration below the PA-IC90 (64 ng/mL) at day 3. There were no slow metabolizers in the placebo arm and 5 in the supplemental arm. In summary, no participants in the placebo arm had dolutegravir trough concentrations below the PA-IC90. Prolonged efavirenz induction effect in CYP2B6 slow metabolizers contributed to lower dolutegravir trough concentrations at day 28 in the supplemental arm. This finding does not support the need for a supplemental dolutegravir dose when switching from a failing first-line efavirenz based regimen.

Pharmacokinetics of standard vs double-dose dolutegravir after switch from efavirenz. Griesel R, Banda C, Zhao Y, et al. CROI 2023, Seattle February 19-22, abstract 507.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Eflornithine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Approximately 80% of oral/intravenous doses of eflornithine are excreted unchanged via the kidneys. No interaction is expected with dolutegravir. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. Clinically significant interactions are not expected with topical preparations as <1% of topically applied eflornithine is systemically absorbed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Elbasvir/Grazoprevir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of multiple doses of elbasvir/grazoprevir and dolutegravir had no clinically relevant effect on the pharmacokinetics of grazoprevir, elbasvir or dolutegravir. Coadministration of dolutegravir (50 mg single dose) and elbasvir + grazoprevir (50 + 200 mg once daily) to 12 subjects decreased elbasvir AUC, Cmax and C24 by 2%, 3% and 2%, respectively, and decreased grazoprevir AUC, Cmax and C24 by 19%, 36% and 14%, respectively. Dolutegravir AUC, Cmax and Ctrough increased by 16%, 22% and14%, respectively. No interaction with lamivudine is expected.

Description:

Coadministration of dolutegravir (50 mg single dose) and grazoprevir (200 mg once daily) decreased grazoprevir Cmax, AUC and C24 by 36%, 19%, and 14%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eltrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Eltrombopag is metabolised by cleavage conjugation (UGTs 1A1 and 1A3) and oxidation (CYPs 1A2 and 2C8) and in vitro data indicate it is an inhibitor of UGTs 1A1 and 1A3. Although eltrombopag could potentially increase dolutegravir exposure, this is unlikely to be of clinical significance. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir alafenamide (EVG/c/FTC/TAF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) and Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Description:

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Genvoya should not be co-administered with other antiretroviral medicinal products. Genvoya should not be administered concomitantly with medicinal products containing lamivudine.

Genvoya Summary of Product Characteristics, Gilead Sciences International Ltd, November 2021.

Genvoya is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration of Genvoya with other antiretroviral medications for treatment of HIV-1 infection should be avoided.

Genvoya Prescribing Information, Gilead Sciences Inc, September 2021.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir-DF (EVG/c/FTC/TDF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) and Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Description:

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Stribild is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products.

Stribild Summary of Product Characteristics, Gilead Sciences International Ltd, November 2021.

Stribild is a complete regimen for the treatment of HIV-1 infection; therefore, Stribild should not be administered with other antiretroviral medications for treatment of HIV-1 infection.

Stribild Prescribing Information, Gilead Sciences Inc, September 2021.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Empagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Dolutegravir is unlikely to affect the metabolism of empagliflozin and empagliflozin is unlikely to affect dolutegravir concentrations as it does not inhibit or induce CYPs and does not inhibit UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Emtricitabine (FTC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Description:

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Emtricitabine should not be taken with medicinal products containing lamivudine. There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.

Emtriva Summary of Product Characteristics, Gilead Sciences Ltd, April 2019.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Emtricitabine/Tenofovir alafenamide (FTC/TAF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Description:

Descovy should not be administered concomitantly with medicinal products containing lamivudine.

Descovy Summary of Product Characteristics, Gilead Sciences Ltd, April 2022.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Emtricitabine/Tenofovir-DF (FTC/TDF, PrEP)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Description:

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Enalapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Dolutegravir is not expected to inhibit OATs and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Enflurane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enflurane is predominantly metabolized by CYP2E1, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Enoxaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is excreted predominantly renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Entecavir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Dolutegravir is not expected to inhibit OATs. In vitro data indicate that dolutegravir inhibits OCT, but is unlikely to cause a clinically relevant drug interaction with entecavir. No pharmacokinetic interactions were observed between entecavir and lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ephedrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase the exposure of ephedrine. There is also potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Epirubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eplerenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eplerenone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Epoprostenol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolyzed in the blood.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eprosartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as eprosartan is largely excreted in bile and urine as unchanged drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ergometrine (Ergonovine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ergometrine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ergotamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ergotamine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Erlotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Erlotinib is mainly metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Erlotinib is a strong inhibitor of UGT1A1 in vitro and could increase dolutegravir concentrations, however, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ertapenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erythromycin is considered to be a moderate inhibitor of CYP3A4 but CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Eslicarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by eslicarbazepine. Although no dosing recommendations are provided for eslicarbazepine, the US Prescribing Information for Dovato does not recommend coadministration with carbamazepine, another anticonvulsant with inducing properties. However, the European label for Dovato recommends that an additional dolutegravir 50 mg tablet, separated by 12 hours from Dovato, can be taken in presence of carbamazepine. This dose adjustment should be maintained for approximately 2 weeks after stopping eslicarbazepine as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is mainly metabolized by CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Estazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. Preliminary data with estradiol administered as feminizing hormone therapy (FHT) to trans women with HIV taking FHT and integrase inhibitors (bictegravir/emtricitabine/tenofovir alafenamide, n=8; dolutegravir/abacavir/lamivudine, n=2) suggest a low probability of clinically relevant drug-drug interactions between FHT and unboosted integrase inhibitor-based ART.

Description:

Serum oestradiol concentrations were determined in trans women with HIV taking feminizing hormone therapy (FHT) and unboosted integrase strand transfer inhibitor-based ART (n=8) versus trans women without HIV taking FHT (n=7). Among participants, the median oral oestradiol dose was 4 mg (range 2-6 mg). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200-735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV). However, further research is needed with larger sample sizes to fully understand the impact of HIV and ART on FHT in trans women with HIV.

Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study. Loutfy M, Lacombe-Duncan A, et al. J Antimicrob Chemother. 2023, 78(11):2653-2659.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Estramustine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estramustine phosphate undergoes rapid dephosphorylation to estramustine which is then oxidized by 17beta-hydroxysteroid dehydrogenases to estromustine. Estramustine and estromustine are subsequently hydrolyzed to estradiol and estrone, respectively. Estradiol is then hydroxylated by CYPs 1A1, 1A2 and 3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ethambutol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Coadministration of ethinyl estradiol (0.035 mg) and dolutegravir (50 mg twice daily) had no clinically relevant effect on the pharmacokinetics of ethinyl estradiol (Cmax decreased by 1%, AUC and Ctrough increased by 3% and 2%). Dolutegravir had no pharmacodynamic effect on luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone. No interaction is expected with lamivudine. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Description:

Coadministration of dolutegravir and ethinylestradiol/norgestimate increased ethinylestradiol AUC by 3% and decreased Cmax by 1%. AUC and Cmax of norgestromin decreased by 2% and 11%. Dolutegravir had no pharmacodynamic effect on luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone. No dose adjustment of oral contraceptives is necessary when co-administered with Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of ethinyl estradiol (0.035 mg) and dolutegravir (50 mg twice daily) to decreased ethinyl estradiol Cmax by 1% and increased AUC and Ctrough by 3% and 2%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

HIV-negative women received ethinylestradiol/norgestimate (0.035/0.25 mg) with and without dolutegravir 50 mg twice daily. Coadministration had no effect (changes of 3% or less) on the AUC, Cmax and Ctrough of ethinylestradiol. AUC, Cmax and Ctrough of norelgestromin (the active metabolite of norgestimate) decreased by 2%, 11% and 7%, respectively. No effect on luteinising hormone, follicle stimulating hormone and progesterone was observed, suggesting that contraceptive efficacy should be maintained if coadministered with dolutegravir.

Song I et al. 20th CROI, Atlanta, March 2013, abstract 535.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ethionamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver with animal studies suggesting involvement of flavin-containing monooxygenases. No interaction is expected with dolutegravir. There is little potential for an interaction with lamivudine via competition for renal elimination pathways as less than 1% of the oral dose is excreted as ethionamide in urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ethosuximide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethosuximide is mainly metabolized by CYP3A4 and does not induce metabolizing enzymes. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etidocaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etidocaine is metabolized by CYP3A4, but dolutegravir and lamivudine do not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etonogestrel (implant)

Quality of Evidence: Very Low

Summary:

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etonogestrel (vaginal ring)

Quality of Evidence: Very Low

Summary:

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etoposide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoposide is partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. Furthermore, etoposide is partly glucuronidated by UGT1A1. Dolutegravir is not expected to inhibit or induce CYPs or UGTs enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Etravirine (ETR)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with etravirine would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration with etravirine without boosted protease inhibitors but no dose adjustment is necessary for etravirine with boosted protease inhibitors. Coadministration of dolutegravir and etravirine (without boosted protease inhibitors) decreased dolutegravir AUC, Cmax and Cmin by 71%, 52% and 88%, respectively. There was no change in etravirine pharmacokinetics. Coadministration of etravirine (with lopinavir/ritonavir) increased dolutegravir AUC, Cmax and Cmin by 11%, 7% and 28%, respectively; there was no change in lopinavir, ritonavir or etravirine pharmacokinetics. Coadministration of etravirine (with darunavir/ritonavir) decreased dolutegravir AUC, Cmax and Cmin by 25%, 12% and 36%, respectively; there was no change in darunavir, ritonavir or etravirine pharmacokinetics. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and etravirine (without boosted protease inhibitors) decreased dolutegravir AUC, Cmax and Cmin by 71%, 52% and 88%, respectively, due to induction of UGT1A1 and CYP3A enzymes. There was no change in etravirine pharmacokinetics. The recommended dose of dolutegravir is 50 mg twice daily for patients taking etravirine without boosted protease inhibitors. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the etravirine without boosted protease inhibitor co-administration (a separate formulation of dolutegravir is available for this dose adjustment). No dose adjustment is necessary for etravirine with boosted protease inhibitors. Coadministration of etravirine (with lopinavir/ritonavir) increased dolutegravir AUC, Cmax and Cmin by 11%, 7% and 28%, respectively; there was no change in lopinavir, ritonavir or etravirine pharmacokinetics. Coadministration of etravirine (with darunavir/ritonavir) decreased dolutegravir AUC, Cmax and Cmin by 25%, 12% and 36%, respectively; there was no change in darunavir, ritonavir or etravirine pharmacokinetics.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) and etravirine (200 mg twice daily) was studied in 15 HIV-negative subjects. Etravirine significantly decreased dolutegravir AUC, Cmax and Ctrough by 70%, 52% and 88%, respectively. When the same doses were given in the presence of lopinavir/ritonavir (400/100 mg twice daily, n=8), dolutegravir pharmacokinetics were not significantly altered. However, when given with darunavir/ritonavir( 600/100 mg twice daily), dolutegravir AUC, Cmax and Ctrough decreased by 25%, 12% and 37%, respectively, but these changes were not considered as clinically significant. The combination of dolutegravir and etravirine alone should be avoided; however dolutegravir may be coadministered with etravirine without a dosage adjustment if lopinavir/ritonavir or darunavir/ritonavir is concurrently administered.

Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir. Song I, Borland J, Min S, et al. Antimicrob Agents Chemother, 2011, 55(7): 3517-21.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eucalyptus globulus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence to suggest that eucalyptus impacts UGTs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Everolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Everolimus is metabolized by CYP3A4 and is a modest inhibitor of CYP3A4 in vivo. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Evolocumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Evolocumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Exemestane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exemestane is metabolized by CYP3A4 and aldoketoreductase. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Exenatide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as exenatide is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ezetimibe

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Famciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Famciclovir is converted to penciclovir by aldehyde oxidase which is then eliminated in the urine, possibly by OAT1. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by different transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Famotidine is eliminated by renal excretion via OAT3 (65-70%) and by metabolic routes (30-35%). Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Felodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fenofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolyzed to an active metabolite, fenofibric acid. In vitro data suggest that fenofibric acid inhibits OAT3. No interaction is expected with dolutegravir. A clinically relevant drug interaction is unlikely with lamivudine as it is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fentanyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fesoterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine does not undergo CYP-mediated metabolism but is a substrate of P-glycoprotein. In vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Finasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fish oils

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion of the parent drug also eliminated unchanged renally. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flibanserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flibanserin is primarily metabolized by CYP3A4 and has been shown to moderately increase the exposure of simvastatin, a CYP3A4 substrate. No interaction is expected with dolutegravir as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily) and could potentially decrease dolutegravir concentrations, but this is unlikely to be of clinical significance as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is mainly eliminated renally by glomerular filtration and is a moderate inhibitor of CYP3A4. A clinically significant interaction is not expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Flucytosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase. This enzyme is also involved in the catabolic pathway of pyrimidine analogs (such as lamivudine) and competition could potentially increase haematological toxicity. Monitor haematological parameters and consider dose reduction if required. No interaction is expected with dolutegravir.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fludarabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludarabine phosphate is rapidly hydrolyzed (non-CYP mediated) to 2F-ara-A, the principal metabolite, which is then eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fludrocortisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flunisolide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide is metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flunitrazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluocinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of fluocinolone.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Fluorouracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is little potential for an interaction with dolutegravir via modulation of, or competition for, metabolic pathways. However, nucleoside analogues such as lamivudine may compete for this metabolic pathway. The clinical relevance of this interaction is unknown.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flurazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluticasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolized by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Folic acid [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Folic acid [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. A pharmacokinetic interaction is unlikely with folic acid itself and dolutegravir or lamivudine. However, folic acid may be administered in a multivitamin preparation which may also contain polyvalent cations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fondaparinux

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Formestane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. Dolutegravir is not expected to induce or inhibit UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Formoterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. Dolutegravir is not expected to inhibit or induce UGT or CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Foscarnet

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as foscarnet is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fosinopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosinopril is hydrolysed by esterases in the GI mucosa and liver. Fosinopril does not inhibit or induce CYP450 enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations, or to inhibit OATs. No interaction is expected with lamivudine as lamivudine is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gabapentin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ganciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by different transporters.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Garlic

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Garlic has been shown to induce intestinal CYP3A4 and/or P-gp and garlic supplements decreased unboosted saquinavir AUC by 50% in a clinical trial and there is a case report of treatment failure due to garlic cloves (six garlic cloves three times weekly) decreasing ritonavir-boosted atazanavir trough concentrations by ~70%. Similarly, concentrations of dolutegravir could be decreased via induction of CYP3A4 and/or P-gp. Patients should be advised against the use of garlic supplements. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gefitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gefitinib is metabolized by CYP3A4 and CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gemcitabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemcitabine is metabolized in the liver by cytidine deaminase to an inactive metabolite. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gemfibrozil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dolutegravir is mainly glucuronidated by UGT1A1 whereas gemfibrozil is mainly glucuronidated by UGT2B7. In vitro data suggest that gemfibrozil inhibits UGT1A1 and UGT1A3 and therefore could potentially increase dolutegravir concentrations. However, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gentamicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gentamicin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gestodene (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

GHB (Gamma-hydroxybutyrate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Gamma-hydroxybutyrate undergoes first pass metabolism. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ginger (Zingiber officinale)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence to suggest that ginger inhibits or induces UGTs.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ginkgo biloba

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ginkgo biloba induces CYP3A4 and may decrease dolutegravir concentrations, but the magnitude and clinical relevance of this potential interaction is difficult to predict as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glecaprevir/Pibrentasvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine alone has not been studied. Coadministration of glecaprevir/pibrentasvir and dolutegravir/lamivudine/abacavir (Triumeq) was evaluated as part of a Phase 1 study and showed no clinically significant interaction with glecaprevir/pibrentasvir. No dose adjustment is required.

Description:

The pharmacokinetics of glecaprevir/pibrentasvir (300/120 mg once daily) coadministered with abacavir/dolutegravir/lamivudine (600/50/300 mg once daily) was studied in 24 healthy subjects. Cmax and AUC for glecaprevir and pibrentasvir decreased by 25-28%, but there was no impact on Cmax and AUC for abacavir, dolutegravir or lamivudine. No dose adjustment is required when glecaprevir/pibrentasvir are coadministered with abacavir, dolutegravir and lamivudine.

Glecaprevir and pibrentasvir interactions with combination antiretroviral regimens. Kosloski MP, Dutta S, Viani RM, et al. Conference on Retroviruses and Opportunistic Infections, Seattle, February 2017, abstract 413.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glibenclamide (Glyburide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gliclazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glimepiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glimepiride is metabolised by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glipizide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is metabolized mainly by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glyceryl trinitrate (Nitroglycerin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2. Glyceryl trinitrate is not known to induce or inhibit CYP450 enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glycopyrronium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Goldenseal root (Hydrastis canadensis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goldenseal has been shown to inhibit CYP3A4 in vitro but not in vivo. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Goserelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goserelin is mainly hydrolyzed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Granisetron is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inhibition of intestinal CYP3A4 by grapefruit juice is unlikely to alter significantly dolutegravir concentrations as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Griseofulvin is a liver microsomal enzyme inducer but a clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys and there is little potential for an interaction via competition with lamivudine for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Halofantrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Halothane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that halothane undergoes oxidation (mainly via CYP2E1 and to a lesser extent CYP2A6) and reduction (via CYP2A6 and CYP3A4). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Heparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Heroin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. When used illicitly, heroin is mainly injected or inhaled through the nose and goes directly in the bloodstream. Heroin is then rapidly deacetylated to 6-monoacetylmorhine (6-MAM) and subsequently to morphine by plasma and liver esterase, respectively. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Dolutegravir and lamivudine do not affect these metabolic pathways.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Hops (Humulus lupulus)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. In vitro data indicate that extracts of hops activate PXR and induce expression of CYP3A4, CYP2B6 and MDR1 genes to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). Based on these results, hop extracts are unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

A botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and postmenopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. AUCs were unaffected, except for alprazolam which decreased by 7.6% suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2, CYP2D6, or CYP3A4/5.

Pharmacokinetic interactions of a hop dietary supplement with drug metabolism in perimenopausal and postmenopausal women. van Breemen RB, Chen L, Tonsing-Carter A, et al. J Agric Food Chem, 2020, 68(18):5212-5220.

Hop extracts were examined both structurally and functionally and were found to induce the expression of drug metabolism and excretion proteins. mRNA levels for CYP3A4, CYP2B6 and MDR1 were increased in a concentration-dependent manner by activating PXR. The efficacy with which hops activated PXR was comparable to that of St John's wort.

Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Teotico DG, Bischof JJ, Peng L, et al. Mol Pharmacol, 2008, 74:1512-1520.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydralazine is metabolised via primary oxidative metabolism and acetylation. Renal elimination of unchanged hydralazine is minimal. No interaction is expected with dolutegravir and there is little potential for interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydrochlorothiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. No interaction is expected with dolutegravir or with lamivudine which is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydrocortisone (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydrocortisone (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of hydrocortisone.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7, whereas dolutegravir is glucuronidated by UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Hydroxycarbamide (Hydroxyurea)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea undergoes metabolism via non-CYP mediated metabolism and is unlikely to affect concentrations of dolutegravir or lamivudine. However, hydroxyurea is not licensed for use in combination with stavudine and didanosine as toxicities including pancreatitis and hepatitis (in some cases fatal) in HIV patients have been reported via post marketing surveillance. Thus, caution and monitoring for side effects is recommended if coadministered with other NRTIs such as lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydroxyzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ibalizumab-uiyk (IBA)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with ibalizumab would be possible from a pharmacokinetic standpoint. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Dolutegravir undergoes mostly hepatic metabolism, and lamivudine is eliminated renally. Ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No interaction studies have been performed. Based on the mechanism of action and target-mediated drug disposition of ibalizumab, it is not expected that ibalizumab will have pharmacokinetic drug-drug interactions with other medicinal products.

Trogarzo Summary of Product Characteristics, Theratechnologies International Ltd, September 2019.

No drug interaction studies have been conducted with ibalizumab-uiyk. Based on ibalizumab-uiyk’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Dose modifications of ibalizumab-uiyk are not required when administered with any other antiretroviral.

Trogarzo US Prescribing Information, Theratechnologies Inc., May 2018.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ibandronic acid (Ibandronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ibuprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ifosfamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Iloprost

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloprost is extensively metabolized via beta oxidation of the carboxyl side chain with only a minor role for CYP metabolism. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Imatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is primarily metabolized by CYP3A4 and to a lesser extent CYPs 1A2, 2D6, 2C9, 2C19. In vitro data indicate that imatinib inhibits CYPs 3A4, 2D6, 2C9, 2C19. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Imipenem/Cilastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and, to a lesser extent, by active tubular secretion. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms as probenecid (an inhibitor of renal tubular excretion) had minimal effect on plasma levels of imipenem.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Indacaterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indacaterol is eliminated partly unchanged (33%) and partly metabolized by CYP3A4 and UGT1A1, and is a weak substrate of P-gp. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolized by CYP450. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. In vitro data suggest that indapamide inhibits OAT3 but lamivudine is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Insulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Nonpegylated interferon alpha appears to be metabolized principally in the kidney. No interaction is expected with dolutegravir and no pharmacokinetic interaction was observed with lamivudine.

Description:

No clinically significant differences in the pharmacokinetics of lamivudine were observed when coadministered with interferon alfa.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The pharmacokinetic interaction between lamivudine (100 mg once daily) and interferon alpha (10 mIU single dose) was studied in 19 HIV-negative subjects. There were no statistically significant differences in any pharmacokinetic parameter for interferon alpha with and without lamivudine. Lamivudine AUC was significantly decreased on the day of IFN-alpha treatment (from 5026 to 4546 ng.h/ml, p<0.001), but returned to previous levels by the following day; Cmax was slightly lower following IFN-alpha, but this was not statistically significant. The small decrease in lamivudine AUC was not considered clinically relevant and there is no requirement for dose modification.

A study of the pharmacokinetic interaction between lamivudine and alpha interferon. Johnson MA, et al. Eur J Clin Pharmacol, 2000, 56: 289-292.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as interleukin-2 is mainly eliminated by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Inula racemosa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There are no indications that Inula racemosa impacts UGTs or P-gp.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Iodine [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Iodine is converted to iodide, which is trapped in the thyroid gland. Iodides are excreted mainly in the urine with smaller amounts excreted in the faeces, sweat and saliva. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and iodine itself. However, iodine administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ipratropium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Irbesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Irbesartan is metabolized by glucuronidation and oxidation (mainly CYP2C9). Dolutegravir is not expected to inhibit or induce UGT or CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Irinotecan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Irinotecan is converted to its active metabolite SN38 via tissue carboxylesterase and to inactive metabolites (APC, NPC) via CYP3A4. SN38 is further inactivated by several UGTs. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Iron supplements (oral)

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Administration of an iron supplement (ferrous fumarate 324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. When taken with food, Dovato and supplements containing iron can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing iron. Note: the extent of chelation depends on the amount of divalent cation; thus, no significant decrease in dolutegravir would be expected when taking small amount of iron, for example as in preparations such as Floradix.

Description:

Coadministration of iron supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 54%, 57% and 56%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing iron can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and56%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. When taken with food, Dovato and supplements containing iron can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=11) decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and 56%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir (n=10) decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. Dolutegravir and iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after iron supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isoflurane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as isoflurane is almost exclusively eliminated unchanged by the lungs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isoniazid

Quality of Evidence: Very Low

Summary:

Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Dolutegravir is unlikely to interfere with this metabolic pathway and no interaction is expected with lamivudine. However, a study of coadministration of dolutegravir and isoniazid with rifapentine was ended early due to intolerance. In healthy volunteers receiving weekly isoniazid and rifapentine, the addition of dolutegravir resulted in flu-like symptoms and LFT elevations in 2 out of 4 patients (with higher than expected isoniazid concentrations), leading to study termination. Limited pharmacokinetic data suggested lower dolutegravir exposure. Intolerance is likely to be related to rifapentine (+/- healthy volunteer status) rather than isoniazid, since in the INSPIRING study, the addition of dolutegravir to daily isoniazid and rifampicin was well tolerated in 69 HIV-TB coinfected adults at 24 week analysis.

Description:

The effect of rifapentine/isoniazid on dolutegravir was evaluated in a prospective trial enrolling 63 Taiwanese adults with HIV on a dolutegravir containing antiretroviral therapy and treated concurrently with 3HP (i.e., rifapentine/isoniazid 900/900 mg once weekly) for latent tuberculosis. The average dolutegravir plasma concentration before 3HP was 1.58 mg/L (IQR, 1.06-2.61 mg/L) and was 0.75 mg/L (IQR, 0.39-1.22 mg/L) four weeks after starting 3HP. At 12 weeks after beginning 3HP, the average dolutegravir trough concentration was 1.12 mg/L (IQR, 0.56-2.33 mg/L). The proportion of trough concentrations above the protein adjusted IC90 (0.064 mg/L) was 100% at baseline, 98.1% at week 4, and 96.2% at week 12. After excluding nine people with HIV who did not complete 3HP treatment, the rate of virological suppression was 96.3% (52/54). Two individuals had just started antiretroviral treatment less than one month before beginning 3HP and had viral loads of 14’000 and 766 copies/mL, respectively. Three individuals were lost to follow-up after completing 3HP treatment. The rates of viral load <50 copies/mL within 6 months after completing 3HP treatment were 98% (50/51) in the per-protocol analysis and 92.1% (58/63) in the intention-to-treat analysis. One individual had a viral load of 725 copies/mL at one month after completing 3HP but he had a viral load of more than 2’000’000 copies/mL at baseline before starting 3HP. This study showed that dolutegravir trough concentrations were mostly (98.1%) above the protein adjusted 90% inhibition concentration (IC90: 0.064 mg/L) across all visits during the twelve doses of 3HP in people with HIV. In addition, the participants maintained a high rate of HIV viral suppression (98%) within 6 months after completing 3HP.

Drug monitoring was conducted for rifapentine among people with HIV receiving dolutegravir containing antiretroviral therapy and latent tuberculosis treatment. Chen JH, Lin YC, Chen CP et al. J Microbiol Immunol Infect, 2024, epub ahead of print.

An open-label, intrasubject drug interaction study in HIV-negative healthy volunteers comprised investigated the pharmacokinetics of dolutegravir once daily alone and with once weekly isoniazid and rifapentine. Of 4 enrolled subjects (3 males, 1 female, age 22-46 years), 3 completed the study and 1 withdrew prior to the 3rd dose of isoniazid/rifapentine. The study was stopped prematurely due to the development of multiple AEs in 2 subjects. In both subjects, flu-like syndrome with symptoms of nausea, vomiting, and fever (Grades 2 and 3) began ~8 hours after the last doses of dolutegravir, rifapentine, and isoniazid and lasted 24-48 hours. One subject required a 24-hour hospitalization for management of orthostatic hypotension (Grade 3). Transaminase elevations (Grades 2-4) occurred in both subjects. Exposure to rifapentine and its active metabolite were similar to reference PK data, but isoniazid exposure was 67-92% higher than expected in the 2 subjects who developed AEs. Limited pharmacokinetic data suggested isoniazid/rifapentine decreased dolutegravir AUC and Cmin by 46% and 74%. Given that flu-like syndrome was reported in <4% of subjects in studies of the efficacy of weekly isoniazid/rifapentine alone, these data suggest that co-administration of dolutegravir and weekly isoniazid/rifapentine should be avoided.

Early termination of a PK study between dolutegravir and weekly isoniazid/rifapentine. Brooks KM, Pau AK, George JM, et al. CROI 2017, Seattle, February 2017, abstract 409a.

INSPIRING (NCT02178592) is a Phase 3b, non-comparative, active control, randomised, open-label study in HIV-1 infected ART-naïve adults (CD4+ ≥50 cells/µL) with drug-sensitive TB. Participants on rifampin-based TB treatment for up to 8 weeks were randomised (3:2) to receive dolutegravir (50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily) or efavirenz (600 mg once daily), with 2 investigator-selected NRTIs for 52 weeks. Of 113 subjects enrolled, 69 were randomised to dolutegravir and 44 to efavirenz. Interim Week 24 results show that dolutegravir 50 mg twice daily appears to be effective and well-tolerated in HIV/TB co-infected adults receiving rifampin-based TB therapy. Rates of IRIS were low. There were no new toxicity signals for dolutegravir and no discontinuations due to liver events.

Safety and efficacy of dolutegravir-based ART in TB/HIV coinfected adults at week 24. Dooley K, Kaplan R, Mwelase N, et al. CROI 2018, Boston, March 2018, abstract 33.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isosorbide dinitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isosorbide dinitrate undergoes extensive first past metabolism, predominantly in the liver, with less than 30% of a dose undergoing subsequent glucuronidation. There is little potential for clinically significant interaction with dolutegravir via competition for glucuronidation pathways. As renal elimination of unchanged drug is a minor pathway, there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isotretinoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isotretinoin is metabolised mainly by CYP2C8 and CYP3A4 with the participation of CYP2B6 and CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Itraconazole is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ivabradine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ivermectin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest ivermectin is predominantly metabolised by CYP3A4 and does not inhibit metabolic enzymes at clinically relevant concentrations. Similarly, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. There is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Kanamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as kanamycin is eliminated unchanged predominantly via glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ketamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ketamine is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 2B6 and 2C9 in the range of concentrations used in anaesthesia. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketoconazole is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Labetalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated by UGTs 1A1 and 2B7. Dolutegravir does not induce or inhibit UGTs in the range of clinical concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lacidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lacosamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacosamide is metabolized to O-desmethyl-lacosamide mainly by CYP2C19 (approximatively 30% of the dose) and is eliminated unchanged through the kidneys (approximately 40% of the dose).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lactulose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Lamivudine (3TC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with additional lamivudine.

Description:

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Epivir should not be taken with any other medicinal products containing lamivudine.

Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lamotrigine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lamotrigine is mainly glucuronidated by UGT1A4. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lapatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lapatinib is metabolized by CYP3A4 and inhibits this same enzyme. Lapatinib does not significantly inhibit renal transporters (OAT, OCT). A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ledipasvir/Sofosbuvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Although concentrations of dolutegravir may increase due to inhibition of P-gp and BCRP by ledipasvir, any increase is unlikely to be clinically significant. Coadministration of lamivudine (in combination with abacavir) and ledipasvir/sofosbuvir had no effect on the pharmacokinetic parameters of lamivudine, ledipasvir or sofosbuvir. Lamivudine Cmax and AUC decreased by 7% and 6% and Cmin increased by 12%; abacavir Cmax and AUC decreased by 8% and 10%. Ledipasvir Cmax, AUC and Cmin increased by 10%, 18% and 26%; sofosbuvir Cmax and AUC increased by 8% and 21%; AUC and Cmin of GS-331007 increased by 5% and 8% with no change in Cmax. No dose adjustment is required.

Description:

Coadministration of ledipasvir/sofosbuvir and lamivudine (with abacavir) had no effect on the pharmacokinetics of lamivudine, ledipasvir or sofosbuvir. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lenalidomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenalidomide undergoes limited metabolism and is eliminated renally. Lenalidomide does not induce or inhibit CYPs, UGTs or drug transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lercanidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Letrozole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Letrozole is metabolised by CYP3A4 and CYP2A6 to carbinol, an inactive metabolite. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Leuprorelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leuprorelin acetate is a peptide that is primarily degraded by peptidases.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levamisole (Ergamisol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Metabolism and elimination of levamisole has not been well characterized. Based on limited information, and single dose use of levamisole, clinically significant interactions are not considered likely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levetiracetam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levetiracetam undergoes enzymatic hydrolysis (non CYP) and is eliminated unchanged in the urine by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levocetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levodopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. In the presence of a peripheral dopa-decarboxylase inhibitor (carbidopa or benserazide) levodopa is metabolised mainly to 3-O-methyldopa by catechol-O-methyltransferase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Levofloxacin is metabolised to a very small extent and is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). No interaction is expected with dolutegravir. In vitro data indicate that levofloxacin inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown given the good tolerability of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with levonorgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (implant)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (IUD)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel intra-uterine device (IUD) has not been studied but there is little potential for an interaction given the local mechanism of action of levonorgestrel.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levonorgestrel (POP)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Levothyroxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linagliptin is mainly eliminated as parent compound in faeces, with metabolism by CYP3A4 representing a minor elimination pathway. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Linezolid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Linezolid undergoes non-CYP mediated metabolism.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Liquorice (Glycyrrhiza glabra)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Glycyrrhizin, the main active component of Glycyrrhiza glabra, is a modest inducer of CYP3A4 and could potentially decrease the exposure of dolutegravir, although to a modest extent as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Liraglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Liraglutide is degraded by endogenous endopeptidases.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lisinopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisinopril is eliminated unchanged renally via glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lithium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys and is freely filtered at a rate that is dependent upon the glomerular filtration rate. No interactions is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is metabolized by CYP2C8 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Lopinavir/ritonavir (LPV/r)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with lopinavir/ritonavir. Coadministration of lopinavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. No change in the pharmacokinetics of lopinavir was observed with stavudine and lamivudine in clinical studies.

Description:

Coadministration of dolutegravir and lopinavir/ritonavir decreased dolutegravir AUC and Cmin by 4% and 6%, due to induction of UGT1A1 and CYP3A enzymes, but there was no change in Cmax. There was no change in lopinavir or ritonavir pharmacokinetics. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (30 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) was studied in 15 HIV-negative subjects. Coadministration had no significant effects on dolutegravir pharmacokinetics (no change in Cmax, 3% decrease in AUC, 2% increase in Ctrough). The authors recommend no dose adjustment when dolutegravir is coadministered with lopinavir/ritonavir. Note, this study was performed with a dose of dolutegravir lower than the licensed one.

The effect of lopinavir/ritonavir and darunavir/ritonavir on the HIV integrase inhibitor S/GSK1349572 in healthy participants. Song I, Min SS, Borland J, et al. J Clin Pharmacol, 2011, 51: 237-242.

Plasma concentrations of lamivudine (300 mg once daily) with lopinavir/ritonavir (400/100 mg twice daily, n=7) or nevirapine (400 mg once daily, n=8) were determined in HIV positive patients. Lamivudine AUC, Cmax and Ctrough were 11%, 21% and 45% higher, respectively in the presence of lopinavir/ritonavir when compared to nevirapine. The changes in lamivudine disposition were not significant.

Pilot pharmacokinetic study of Human Immunodeficiency Virus-infected patients receiving tenofovir disoproxil fumarate (TDF): Investigation of systemic and intracellular interactions between TDF and abacavir, lamivudine, or lopinavir-ritonavir. Pruvost A, Negredo E, Théodoro F, et al. Antimicrob Agents Chemother, 2009, 53(5): 1937-1943.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Loratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lorazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorazepam is mainly glucuronidated (by UGTs 2B15, 2B4, 2B7, 1A7, 1A10). Dolutegravir is mainly glucuronidated by UGT1A1 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lormetazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated (possibly by UGTs 2B15, 1A9 and 2B7). Dolutegravir is mainly glucuronidated by UGT1A1 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Losartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lovastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

LSD (Lysergic acid diethylamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. LSD (lysergic acid diethylamide) is metabolized to O-H-LSD and N-desmethyl-LSD partly by CYP (unknown isoenzyme).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lumefantrine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Lumefantrine is metabolized predominantly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of dolutegravir alone (50 mg once daily) and artemether-lumefantrine to 7 subjects had no clinically significant effect on the pharmacokinetics of artemether or lumefantrine (Cmax and AUC increased by 12% and 10%). No interaction is expected with lamivudine. Standard doses of artemether-lumefantrine can be used in patients receiving 50 mg dolutegravir once daily.

Description:

Coadministration of dolutegravir and artemether-lumefantrine was studied in 7 HIV-negative subjects. Subjects received standard clinical treatment doses of artemether-lumefantrine for 3 days, followed by 6 days of dolutegravir (50 mg once daily, to reach steady state) plus 3 days of artemether-lumefantrine plus dolutegravir. Artemether Cmax decreased by 13% but AUC increased by 5%; Cmax and AUC of dihydroartemisinin both decreased 8%. Lumefantrine Cmax and AUC increased by 12% and 10%); Cmax and AUC of desbutyl-lumefantrine both decreased by 4%. The authors conclude that standard doses of artemether-lumefantrine can be used in patients receiving 50 mg dolutegravir once daily.

Dolutegravir interactions with artemether-lumefantrine and amodiaquine-artesunate. Walimbwa SI, Lamorde M, Waitt C, et al. Conference on Retroviruses and Opportunistic Infections, March 2018, Boston, Abstract 459.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Macitentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolized mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Magnesium supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Magnesium is eliminated in kidney, mainly by glomerular filtration. Dolutegravir binds to divalent cations, such as magnesium, and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. No interaction is expected with lamivudine. When taken with food, Dovato (dolutegravir/lamivudine) and supplements containing magnesium can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing magnesium.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Malabar nut tree (Justicia adhatoda, Adhatoda vasica)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Limited data are available on the effect of malabar nut tree on drug metabolism. In vitro data with leaf extracts suggest it could act as an inducer of phase I and phase II metabolic enzymes although the clinical relevance has not been evaluated. In the absence of data, caution is recommended and TDM of dolutegravir should be considered if available. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Mannitol

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. Mannitol is metabolised only very slightly, if at all, to glycogen in the liver and is predominantly eliminated unchanged via glomerular filtration. No interaction is expected with dolutegravir. However, coadministration may decrease lamivudine concentrations. When possible, avoid chronic coadministration of Dovato with medicinal products containing osmotic acting poly-alcohols or monosaccharide alcohols (e.g., mannitol). Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.

Description:

When possible, avoid chronic coadministration of Dovato with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (eg: xylitol, mannitol, lactitol, maltitol). Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided. Coadministration of soribitol (3.2, 10.2, 13.4 g) and lamivudine (oral solution, 300 mg single dose) decreased lamivudine AUC and Cmax by 14%, 32%, 36% and 28%, 52% and 55%, respectively.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Maprotiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Maraviroc (MVC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with maraviroc (dosed at 300 mg twice daily) would be possible from a pharmacokinetic standpoint. Maraviroc is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) increased lamivudine AUC (14%) and Cmax (16%), but is not considered to be clinically significant. Maraviroc concentrations were not measured, but no effect is expected.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The effect of maraviroc (300 mg twice daily) on lamivudine/zidovudine (150/300 mg, twice daily) was studied in 11 healthy volunteers. Lamivudine AUC and Cmax increased by 14% and 16%, respectively. Zidovudine AUC and Cmax decreased by 2% and 8%, respectively. These changes in NRTI exposure are not clinically significant.

Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinylestradiol/levonorgestrel in healthy volunteers. Abel S, Russell D, Whitlock L, et al. Br J Clin Pharmacol, 2008, 65(S1): 19-26.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mebendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mebendazole is predominantly metabolized in the liver. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. Renal excretion of unchanged mebendazole appears to be minimal and there is little potential for an interaction with lamivudine via competition for active renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Medroxyprogesterone (depot injection)

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of medroxyprogesterone and lamivudine (with zidovudine and efavirenz) did not the affect the pharmacokinetics of medroxyprogesterone. Coadministration with a medroxyprogesterone sub-cutaneous depot injection has not been studied.

Description:

The pharmacokinetics of medroxyprogesterone (IM depot injection) were studied in 15 HIV+ women receiving zidovudine, lamivudine and efavirenz. When compared to data obtained from 15 HIV+ women not receiving antiretroviral therapy, there were no differences in medroxyprogesterone AUC, Cmin, half life or clearance. Side effects related to medroxyprogesterone were not increased. Thus, it is likely that this combination regimen would not decrease medroxyprogesterone’s contraceptive effectiveness. The effect on medroxyprogesterone on the pharmacokinetics of zidovudine, lamivudine or efavirenz was not assessed.

Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Nanda K, Amaral E, Hays M, et al. Fertil Steril. 2008, 90(4): 965-971.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Medroxyprogesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with medroxyprogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mefenamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefenamic acid is metabolized by CYP2C9 and additionally glucuronidated by UGT2B7 and 1A9. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mefloquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefloquine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Megestrol acetate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as megestrol acetate is mainly eliminated in the urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Meglumine antimoniate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meglumine antimoniate is predominantly eliminated unchanged via renal glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via completion with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Melarsoprol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Based on limited data concerning metabolism, elimination and toxicity of melarsoprol, there is little potential for interaction, although due to the lack of available data, vigilance is required if administering melarsoprol with antiretrovirals. It is unknown whether urinary metabolites of melarsoprol, such as arsenic, are excreted via active renal mechanisms, however a clinical study has reported that urinary pharmacokinetic parameters are not predictive of toxicity or therapeutic efficacy. Therefore lamivudine has little potential to effect melarsoprol treatment via competition for renal elimination mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Menthol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence to suggest that menthol impacts UGTs or P-gp.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mephedrone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Mephedrone is metabolized mainly by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mercaptopurine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mercaptopurine is predominantly metabolised by xanthine oxidase. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Meropenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporters OAT3/OAT1. Dolutegravir is not expected to inhibit these renal transporters and lamivudine is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mesalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolized to N-acetyl-mesalazine by N-acetyltransferase. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mesna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesna is rapidly oxidised to its only metabolite, mesna disulphide via the physiological cysteine system. Approximately 32% and 33% of an administered dose is eliminated in the urine in 24 hours as mesna and mesna disulphide respectively. No interaction is expected with dolutegravir. In vitro data suggest that mesna is a substrate of the OAT1, OAT3 and OAT4 renal transporters whereas lamivudine is transported by OCT2.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Metformin

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. Metformin is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OCT2. A clinically relevant drug interaction with lamivudine is unlikely in the range of observed clinical concentrations. Coadministration of metformin (500 mg twice daily) was studied with dolutegravir alone (50 mg once or twice daily) in 15 subjects. Coadministration with once daily dolutegravir increased metformin Cmax and AUC by 66% and 79%, whereas coadministration with twice daily dolutegravir increased metformin Cmax and AUC by 111% and 145%. A dose adjustment of metformin should be considered when starting and stopping coadministration of Dovato with metformin in order to maintain glycaemic control. Monitoring renal function during coadministration and monitoring blood glucose when starting and stopping coadministration is recommended. As metformin is eliminated renally, patients with moderate renal impairment may be at increased risk for lactic acidosis due to increased metformin concentrations.

Description:

Coadministration of dolutegravir (50 mg once daily) and metformin increased metformin AUC and Cmax by 79% and 66%. Coadministration of dolutegravir (50 mg twice daily) and metformin increased metformin AUC and Cmax by 145% and 111%. There was no effect on dolutegravir pharmacokinetics at either dose. A dose adjustment of metformin should be considered when starting and stopping coadministration of Dovato with metformin, to maintain glycaemic control. Metformin is eliminated renally and, therefore, it is of importance to monitor renal function when co-treated with Dovato. This combination may increase the risk for lactic acidosis in patients with moderate renal impairment (stage 3a creatinine clearance 45– 59 mL/min) and a cautious approach is recommended. Reduction of the metformin dose should be highly considered.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dolutegravir, a component of Dovato, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as metformin. Refer to the prescribing information of metformin for assessing the benefit and risk of concomitant use of Dovato and metformin. Coadministration of metformin (500 mg twice daily) was studied with dolutegravir (50 mg once or twice daily). Coadministration with once daily dolutegravir increased metformin Cmax and AUC by 66% and 79%, whereas coadministration with twice daily dolutegravir increased metformin Cmax and AUC by 111% and 145%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Co-administration of metformin (500 mg twice daily) was studied with dolutegravir alone (50 mg once or twice daily) in 15 subjects. Co-administration of dolutegravir 50 mg once daily increased metformin AUC and Cmax by 79% and 66%, respectively, whereas dolutegravir 50 mg twice daily increased metformin area AUC and Cmax by 145% and 111%, respectively. Co-administration of dolutegravir and metformin was well tolerated. In vitro, dolutegravir was not a clinically relevant inhibitor of OCT1, OCT3, multidrug and toxin extrusion protein 1, multidrug and toxin extrusion protein 2-K, or plasma membrane monoamine transporter. Increased metformin plasma exposure can be partially explained by OCT2 inhibition by dolutegravir. It is recommended that dose adjustments of metformin be considered to maintain optimal glycemic control when patients are starting/stopping dolutegravir while taking metformin.

Song IH, Zong J, Borland J, et al. The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects. J Acquir Immune Defic Syndr. 2016 Aug 1;72(4):400-7.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Coadministration of methadone (16-150 mg) and dolutegravir (50 mg twice daily) had no effect on methadone Cmax, and decreased AUC and Ctrough by 2% and 1%, respectively. No effect on methadone pharmacokinetics was observed following a single dose of lamivudine/zidovudine (150/300 mg) to subjects stable on methadone maintenance therapy (AUC and Cmax increased by ~2% and Cmin decreased by ~3%). No dose adjustment is necessary for methadone, dolutegravir or lamivudine.

Description:

Coadministration of methadone (16-150 mg) and dolutegravir (50 mg twice daily) had no effect on methadone Cmax and decreased AUC and Ctrough by 2% and 1%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg twice daily) and methadone was studied in 11 HIV-negative subjects stable on methadone maintenance therapy. No effect of dolutegravir on methadone pharmacokinetics was observed – the AUC and Cmin of total methadone both decreased by 2% and there was no change in Cmax. The AUC, Cmax and Cmin of R-methadone decreased by 5%, 3% and 5%, respectively; whereas AUC, Cmax and Cmin of S-methadone increased by 1%, 3% and 1%, respectively.

Dolutegravir does not affect methadone pharmacokinetics in opioid-dependent, HIV-seronegative subjects. Song I, Mark S, Chen S, et al. Drug Alcohol Depend, 2013, 133(2):781-4.

Methadone pharmacokinetics were determined prior to and following a single dose of lamivudine/zidovudine (150/300 mg) in 16 HIV-negative subjects stable on methadone maintenance therapy. No significant differences in the AUC, Cmax, clearance, volume of distribution or half life were detected (AUC and Cmax increased by ~2% and Cmin decreased by ~3%).

The pharmacokinetics of methadone following coadministration with a lamivudine/zidovudine combination tablet in opiate-dependent subjects. Rainey PM, et al. Am J. Addict, 2002, 11: 66-74.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methamphetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Methamphetamine is mainly metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methotrexate (Amethopterin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion (OAT1, OAT3 mediate methotrexate transport in the kidney whereas MRP4 and BCRP mediate methotrexate efflux in the urine). No interaction is expected with dolutegravir. There is no risk for competition for active renal transport mechanisms as lamivudine is eliminated by other renal transporters. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Description:

Methotrexate concentrations were determined in 43 HIV+ patients treated with ARVs and chemotherapy containing high dose methotrexate (3g/m2). Methotrexate elimination half-life was not affected by use of NNRTIs, integrase inhibitors or NRTIs (tenofovir /emtricitabine or abacavir/lamivudine).

The pharmacokinetics of high‑dose methotrexate in people living with HIV on antiretroviral therapy. Dalla Pria A, Bendle M, Ramaswami R, et al. Cancer Chemother Pharmacol, 2016, 77:653-657.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methyldopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged, and as the mono-O-sulfate conjugate. No interaction is expected with dolutegravir and there is little potential for interaction with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methylphenidate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolized by cytochrome P450s to a clinically relevant extent and does not inhibit cytochrome P450s.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methylprednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Metoclopramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Metolazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metolazone is largely excreted unchanged in the urine. No interaction is expected with dolutegravir and there is no evidence that metolazone inhibits the renal transporters involved in the elimination of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Metoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Metronidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mexiletine is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolized by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Miconazole inhibits CYP2C9 and CYP3A4 but a clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Midazolam (oral)

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of midazolam (3 mg) and dolutegravir alone (25 mg once daily) to 10 subjects had no clinically relevant effect on the pharmacokinetics of midazolam (AUC decreased by 5%). No interaction is expected with lamivudine.

Description:

In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of midazolam (3 mg) and dolutegravir (25 mg once daily) decreased midazolam AUC by 5%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (25 mg once daily) and midazolam (3 mg single oral dose) was studied in 10 healthy subjects. Plasma midazolam AUC values were similar for the coadministration of midazolam with 25 mg dolutegravir (15.4 ng.h/ml on day 10 [CV, 41%]) and administration of midazolam alone (16.3 ng.h/ml on day1 [CV, 23%]); the GLS mean ratio was 0.945 (90% CI, 0.815, 1.10). These data demonstrate that dolutegravir does not induce or inhibit the CYP3A isozyme in vivo.

Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Min S, Song I, Borland J, et al. Antimicrob Agents Chemother. 2010; 54(1):254-8.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of midazolam (3 mg) and dolutegravir alone (25 mg once daily) to 10 subjects had no clinically relevant effect on the pharmacokinetics of midazolam (AUC decreased by 5%). No interaction is expected with lamivudine.

Description:

In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of midazolam (3 mg) and dolutegravir (25 mg once daily) decreased midazolam AUC by 5%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (25 mg once daily) and midazolam (3 mg single oral dose) was studied in 10 healthy subjects. Plasma midazolam AUC values were similar for the coadministration of midazolam with 25 mg dolutegravir (15.4 ng.h/ml on day 10 [CV, 41%]) and administration of midazolam alone (16.3 ng.h/ml on day1 [CV, 23%]); the GLS mean ratio was 0.945 (90% CI, 0.815, 1.10). These data demonstrate that dolutegravir does not induce or inhibit the CYP3A isozyme in vivo.

Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Min S, Song I, Borland J, et al. Antimicrob Agents Chemother. 2010; 54(1):254-8.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mifepristone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. CYP3A4 is thought to be the main enzyme involved in mifepristone metabolism and in vitro studies suggest that mifepristone may inhibit CYP3A4. Renal excretion of mifepristone is thought to account for approximately 10% of an oral dose A clinically significant interaction with dolutegravir is not expected as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentration and CYP3A does not play a major role in dolutegravir metabolism. There is little potential for interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Milk thistle (Silybum marianum, silymarin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drug-drug interaction studies suggest that milk thistle has limited clinical impact on substrates of CYP3A, P-gp, UGT and OATP.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Milnacipran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Miltefosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Based on limited data concerning metabolism, elimination and toxicity of miltefosine, there is little potential for interaction. In vitro studies have shown that interactions between miltefosine and drugs which are metabolised by cytochrome P450, glucuronidated or otherwise conjugated are unlikely. The main metabolic pathway of miltefosine appears to be mediated by phospholipases. Only a very small proportion of an administered dose of miltefosine is excreted in the unchanged form, therefore there is little potential for an interaction with lamivudine via competition for renal elimination pathways. A case report describes two patients who were taking a regimen of stavudine, lamivudine and nevirapine who were safely and effectively treated with miltefosine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Minaxolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minaxolone undergoes hepatic metabolism, but dolutegravir and lamivudine do not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mirabegron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirabegron is metabolized by multiple pathways including hydrolysis, glucuronidation and oxidation by CYP2D6 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Misoprostol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Misoprostol is predominantly metabolised via fatty acid oxidising systems.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mitoxantrone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Mitoxantrone is metabolized to inactive carboxylic acid derivatives possibly by CYP450. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Modafinil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Modafinil is largely metabolized by hydrolysis (esterase-mediated) and to a lesser extent by CYP3A4-mediated oxidative metabolism. Dolutegravir does not inhibit or induce CYP450 enzymes. Modafinil is a moderate inducer of CYP3A4, but is unlikely to cause a clinically significant reduction of dolutegravir based on the interaction study with rifabutin, another moderate inducer. No interaction is expected between lamivudine and modafinil.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolized by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Moxifloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. In vitro studies indicate that dolutegravir does not inhibit UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Multivitamins

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir AUC by 33%. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and 2B7. No interaction is expected with dolutegravir as it is primarily glucuronidated by UGT1A1 and is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Naftidrofuryl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naftidrofuryl is metabolized to 3 major metabolites primarily by plasma pseudo-choline esterases

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Naloxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naloxone is mainly glucuronidated by UGT2B7 and does not induce or inhibit CYP450 enzymes. Dolutegravir is not expected to inhibit or induce UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Naltrexone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies have shown that neither naltrexone, nor its main metabolite (6-beta-naltrexol), is metabolized by CYP450 enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nandrolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nandrolone is metabolised in the liver by alpha-reductase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Naproxen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. Naproxen and its metabolites are primarily eliminated by the kidney. In vitro data suggest that naproxen is a weak inhibitor of the renal transporter OCT2. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nateglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is mainly metabolized by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nebivolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nefazodone is metabolized mainly by CYP3A4 and is also an inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Neostigmine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Neostigmine is thought to undergo a degree of hepatic metabolism, although the mechanisms are unknown. Metabolism also occurs via hydrolysis by cholinesterase and up to 50% of a dose is excreted unchanged via the kidneys. There is little potential for a clinically significant interaction with antiretrovirals via liver enzyme modification and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Nevirapine (NVP)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with nevirapine would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration as nevirapine, an inducer of CYP3A4, could potentially decrease dolutegravir concentrations. Note, the bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such as nevirapine oral suspension.

Description:

Coadministration of dolutegravir and nevirapine has not been studied but a similar reduction in dolutegravir exposure as observed with efavirenz is expected, due to induction. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with nevirapine. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the nevirapine co-administration.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.

Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4, and to a lesser extent by CYPs 2D6 and 2C8, and inhibits CYP3A4. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Niclosamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After oral administration, absorption of niclosamide is considered minimal.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nicorandil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of nicorandil takes place mainly via denitration with the denitrated product then merging into the nicotinamide pathway.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Nicotinamide (Niacinamide) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which is then metabolized by xanthine oxidase and aldehyde oxidase. Renal elimination of unchanged nicotinamide is minimal. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and nicotinamide itself. However, nicotinamide administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nifedipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nifurtimox

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Based on limited data concerning metabolism, elimination and toxicity of nifurtimox, there is little potential for interaction, although due to the lack of data, vigilance is required if administering nifurtimox with antiretrovirals. Nifurtimox appears to be biotransformed partially at a cytochrome P450 level but mostly by NADPH P450 reductase, with <1% of a dose excreted unchanged via the kidneys. No interaction is expected with dolutegravir and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nilotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Nilotinib is metabolized by CYP3A4 and inhibits this same enzyme. Furthermore, in vitro data indicate that nilotinib inhibits UGT1A1. Nilotinib could potentially increase dolutegravir concentrations via UGT1A1 and CYP3A4 inhibition. However, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nimesulide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nimesulide is extensively metabolized in the liver following multiple pathways including CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nisoldipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nitrendipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolized mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nitrofurantoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolized in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug. In vitro studies indicate that dolutegravir does not inhibit UGTs at clinically relevant concentrations. As renal excretion is not the predominant mechanism of elimination, there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nitrous oxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Most inhaled nitrous oxide is rapidly eliminated unchanged through the lungs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norelgestromin (patch)

Quality of Evidence: Very Low

Summary:

Coadministration with transdermally delivered norelgestromin/ethinylestradiol has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolized to norgestrel (possibly by CYP3A4). Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norethisterone [Norethindrone] (COC)

Quality of Evidence: Very Low

Summary:

Coadministration of a combined oral contraceptive (COC) containing norethisterone and mestranol or ethinylestradiol has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Mestranol is rapidly and almost completely converted to ethinylestradiol by CYP2C9; ethinylestradiol is mainly metabolised by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norethisterone [Norethindrone] (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with norethisterone as hormone replacement therapy (HRT) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norethisterone [Norethindrone] (IM depot injection)

Quality of Evidence: Very Low

Summary:

Coadministration of a norethisterone IM depot injection has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norethisterone [Norethindrone] (POP)

Quality of Evidence: Very Low

Summary:

Coadministration of a norethisterone progestogen-only pill (POP) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norgestimate (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Coadministration of dolutegravir (50 mg twice daily) and a combined oral contraceptive (COC) containing norgestimate/ethinylestradiol (0.25/0.035 mg) had no clinically relevant effect on the pharmacokinetics of norgestimate, norgestromin (the active metabolite of norgestimate) or ethinylestradiol. Dolutegravir had no pharmacodynamic effect on luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and ethinylestradiol/norgestimate increased ethinylestradiol AUC by 3% and decreased Cmax by 1%. AUC and Cmax of norgestromin decreased by 2% and 11%. Dolutegravir had no pharmacodynamic effect on luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone. No dose adjustment of oral contraceptives is necessary when co-administered with Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of norgestimate (0.25 mg) and dolutegravir (50 mg twice daily) decreased norelgestromin Cmax, AUC and Ctrough by 11%, 2% and 7%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

HIV-negative women received ethinylestradiol/norgestimate (0.035/0.25 mg) with and without dolutegravir 50 mg twice daily. Coadministration had no effect (changes of 3% or less) on the AUC, Cmax and Ctrough of ethinylestradiol. AUC, Cmax and Ctrough of norelgestromin (the active metabolite of norgestimate) decreased by 2%, 11% and 7%, respectively. No effect on luteinising hormone, follicle stimulating hormone and progesterone was observed, suggesting that contraceptive efficacy should be maintained if coadministered with dolutegravir.

Song I et al. 20th CROI, Atlanta, March 2013, abstract 535.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norgestrel (COC)

Quality of Evidence: Very Low

Summary:

Coadministration of a combined oral contraceptive (COC) containing norgestrel/ethinylestradiol has not been studied. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir does not inhibit or induce CYP450 or UGT enzymes and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norgestrel (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with norgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolized mainly by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nystatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ofloxacin is eliminated unchanged in the kidneys by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with ofloxacin. Lamivudine is eliminated by OCT2 and in vitro data indicate that ofloxacin inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown given the good tolerability of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Olanzapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolized mainly by CYP1A2, but also by glucuronidation (UGT1A4). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Olmesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Olodaterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olodaterol is metabolized by CYP2C8, CYP2C9, is glucuronidated via several UGTs, and is a substrate of P-gp. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ombitasvir/Paritaprevir/r

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Coadministration of ombitasvir/paritaprevir/ritonavir + dasabuvir and dolutegravir alone (50 mg once daily) or abacavir/lamivudine alone (600/300 mg once daily) was studied in 12 HIV/HCV-negative subjects and had no clinically significant effect on the pharmacokinetics of ombitasvir, paritaprevir, ritonavir, dasabuvir, dolutegravir or lamivudine. No dose adjustment is required.

Description:

Coadministration of ombitasvir/paritaprevir/ritonavir ± dasabuvir with dolutegravir (n=4) was studied in a retrospective observational study in co-infected HIV and HCV patients. There was no significant effect on dolutegravir Ctrough, however the effect on ombitasvir, paritaprevir, ritonavir or dasabuvir was not studied.

Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world. Tempestilli M, Fabbri G, Mastrorosa I et al. J Antimicrob Chemother, 2018, 73(1):160-164.

Coadministration of ombitasvir/paritaprevir/ritonavir + dasabuvir and abacavir/lamivudine (600/300 mg once daily) was studied in 12 HIV/HCV-negative subjects. During coadministration abacavir exposures were up to 13% lower; lamuvidine Cmax and AUC were up to 13% lower and Ctrough was 29% higher. Exposure of ombitasvir and dasabuvir were up to 18% lower, and paritaprevir and ritonavir Ctrough both decreased by 34%. No dose adjustment is recommended for ombitasvir/paritaprevir/ritonavir + dasabuvir or abacavir/lamuvudine during coadministration.

Drug-drug interactions of ombitasvir/paritaprevir/r plus dasabuvir with dolutegravir or abacavir plus lamivudine. Khatn A, Trinh R, Zhao W, et al. 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington DC, May 2015, Abstract 57.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ombitasvir/Paritaprevir/r + Dasabuvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Coadministration of ombitasvir/paritaprevir/ritonavir + dasabuvir and dolutegravir alone (50 mg once daily) or abacavir/lamivudine alone (600/300 mg once daily) was studied in 12 HIV/HCV-negative subjects and had no clinically significant effect on the pharmacokinetics of ombitasvir, paritaprevir, ritonavir, dasabuvir, dolutegravir or lamivudine. No dose adjustment is required.

Description:

Coadministration of ombitasvir/paritaprevir/ritonavir ± dasabuvir with dolutegravir (n=4) was studied in a retrospective observational study in co-infected HIV and HCV patients. There was no significant effect on dolutegravir Ctrough, however the effect on ombitasvir, paritaprevir, ritonavir or dasabuvir was not studied.

Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world. Tempestilli M, Fabbri G, Mastrorosa I et al. J Antimicrob Chemother, 2018, 73(1):160-164.

Coadministration of ombitasvir/paritaprevir/ritonavir (25/150/100 mg, once daily) and dasabuvir (250 mg, twice daily) with abacavir (300 mg once daily) and lamivudine (300 mg, once daily) was studied in 12 healthy volunteers. Abacavir Cmax and AUC decreased by 13% and 6%, respectively; abacavir Ctrough could not be determined as concentrations were below the lower limit of quantification for the majority of subjects. Lamivudine Cmax and AUC decreased by 22% and 12%, respectively, while Ctrough increased by 29%. The changes in abacavir and lamivudine pharmacokinetic parameters are not expected to influence the efficacy or safety profiles of either medication. Ombitasvir Cmax, AUC and Ctrough decreased by 18%, 9% and 8%, respectively; paritaprevir Cmax, AUC and Ctrough decreased by 16%, 18% and 27%, respectively; ritonavir Cmax, AUC and Ctrough decreased by 12%, 12% and 7%. Dasabuvir Cmax, AUC and Ctrough decreased by 6%, 9% and 5%. None of the changes in pharmacokinetic parameters for ombitasvir, paritaprevir, ritonavir or dasabuvir were considered clinically significant. The authors conclude that ombitasvir/paritaprevir/r + dasabuvir does not have any clinically relevant drug-drug interactions with abacavir and lamivudine and no dose adjustments are required.

Drug-drug interaction between the direct-acting antiviral regimen of ombitasvir-paritaprevir-ritonavir plus dasabuvir and the HIV antiretroviral agent dolutegravir or abacavir plus lamivudine. Khatri A, Trinh R, Zhao W, et al. Antimicrob Agents Chemother, 2016, 60(10): 795-816.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Omeprazole is mainly metabolized by CYP2C19 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of omeprazole (40 mg once daily) and dolutegravir (50 mg single dose) had no clinically significant effect on the pharmacokinetics of dolutegravir (Cmax, AUC and Ctrough decreased by 8%, 3% and 5%, respectively). No interaction is expected with lamivudine.

Description:

Coadministration with omeprazole had no effect on dolutegravir pharmacokinetics. No dosage adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of omeprazole (40 mg once daily) and dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC and Ctrough by 8%, 3% and 5%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Orlistat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Orlistat should only be used with dolutegravir/lamivudine if separated by 4-5 hours. Orlistat reduces dietary fat absorption and may affect the absorption of antiretrovirals (especially if lipophilic). [Note: this interaction is not specific for dolutegravir/lamivudine, but for any medication taken with orlistat.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oseltamivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oseltamivir is converted to oseltamivir carboxylate by esterases. The latter is excreted in the urine by glomerular filtration and tubular secretion by OAT1. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by different transporters.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Oxaliplatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Oxaliplatin undergoes non enzymatic biotransformation and is eliminated renally via OCT2 and MATE2-K. In vitro data indicate that dolutegravir is a moderate inhibitor of OCT2. Although inhibition of OCT2 may represent an advantage in terms of nephrotoxicity, inhibition may impair the response to oxaliplatin chemotherapy. OCT2 is expressed in some tumour cells where it will facilitate the entry of cytostatic agents such as oxaliplatin (but not cisplatin) inside the tumour cell. Dolutegravir, an inhibitor of OCT2, could potentially decrease the efficacy of oxaliplatin. Oxaliplatin and lamivudine could potentially compete for OCT2 which could slow their elimination. Monitor side effects.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxamniquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Oxamniquine is thought to be predominantly metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Renal excretion of unchanged oxamniquine is minimal and there little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxandrolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxandrolone is mainly eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated (by UGTs 2B15, 1A9 and 2B7). Dolutegravir is mainly glucuronidated by UGT1A1 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by oxcarbazepine. The US Prescribing Information for Dovato advises to avoid coadministration due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping oxcarbazepine as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine. Limited data from a small number of patients showed TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges and trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs.

Description:

Coadministration with oxcarbazepine has not been studied but a decrease in dolutegravir is expected due to induction of UGT1A1 and CYP3A enzymes. A similar reduction in exposure as observed with carbamazepine is expected. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with oxcarbazepine . As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with oxcarbazepine (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The drug-drug interactions between antiretrovirals and carbamazepine or oxcarbazepine were evaluated in a clinical setting using therapeutic drug monitoring (TDM) trough concentrations collected from HIV+ patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. Eleven HIV-positive patients prescribed carbamazepine (n=7) or oxcarbazepine (n=4) were identified. All the TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges. Trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs (191 ± 78 versus 1096 ± 510 ng/mL). Co-administration of carbamazepine or oxcarbazepine with dolutegravir should be avoided owing to the potential risk of virological failure; the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

Drug-drug interactions between antiretrovirals and carbamazepine/oxcarbazepine: a real-life investigation. Cattaneo D, Baldelli S, Cozzi V, et al. Ther Drug Monit. 2020;42(2):330-334.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxprenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised by glucuronidation. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxybutynin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxybutynin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally by CYP3A and CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxytocin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elimination of oxytocin occurs via the liver, kidney, functional mammary gland and oxytocinase. The plasma half-life is approximately five minutes. However, as few data are available, care should be taken when administering oxytocin with antiretrovirals

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Paclitaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4. In vitro data suggest that paclitaxel activates PXR and therefore could potentially decrease dolutegravir concentrations via induction of UGT1A1. Monitor response to antiretroviral therapy. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly OCT), with minimal metabolism occurring via CYP2D6 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with paliperidone. There is little potential for an interaction with lamivudine via competition for active renal transport mechanisms given the possible limited role of OCT in paliperidone’s elimination.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolized by CYP2C19 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Para-aminosalicylic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that dolutegravir inhibits OCT2 and may increase the exposure of para-aminosalicylic acid. In addition, as para-aminosalicylic acid and lamivudine are predominantly renally eliminated, including by active tubular secretion, there is potential for competition for elimination via renal transport proteins, which may lead to increased concentrations of either drug. The clinical relevance of this interaction is unknown.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Paromomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paromomycin is not metabolized and is eliminated unchanged by renal glomerular filtration. No interaction with dolutegravir is expected and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Paroxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYP2D6 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pazopanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pazopanib is metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C8. Dolutegravir is not expected to inhibit or induce CYPs enzymes at clinically relevant concentrations. In vitro data indicate that pazopanib inhibits UGT1A1 and therefore could potentially increase dolutegravir concentrations. However, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Dolutegravir is primarily metabolised by UGT1A1, with some contribution from CYP3A. These pathways are not affected by peginterferon alfa-2a. Results from pharmacokinetic substudies of phase III trials demonstrated no effect of lamivudine on the pharmacokinetics of peginterferon alfa-2a in HBV patients. However, hepatic decompensation (some fatal) has occurred rarely in cirrhotic HIV/HCV co-infected patients receiving NRTI-containing HIV therapy and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and NRTIs should be closely monitored for treatment-associated toxicities, especially hepatic decompensation and anaemia.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Peginterferon alfa-2b

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Dolutegravir is primarily metabolised by UGT1A1, with some contribution from CYP3A. These pathways are not affected by peginterferon alfa-2b. In a trial with another pegylated interferon alfa, no evidence of a pharmacokinetic or pharmacodynamic (e.g., loss of HIV/HCV virologic suppression) interaction was seen when lamivudine and ribavirin were co-administered to 18 HIV/HCV co-infected subjects as part of a multidrug regimen. However, hepatic decompensation (some fatal) has occurred rarely in cirrhotic HIV/HCV co-infected patients receiving NRTI-containing HIV therapy and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and NRTIs should be closely monitored for treatment-associated toxicities, especially hepatic decompensation and anaemia.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Penicillamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although metabolism of penicillamine is not fully elucidated, multiple mechanisms and sites of metabolism are thought to be involved. There is, low potential for clinically significant interactions with dolutegravir or with lamivudine via competition for active renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Penicillins

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Dolutegravir is not expected to inhibit OAT and lamivudine is eliminated by different transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pentamidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The exact metabolic pathway of pentamidine has not been clearly established. Data from animal studies suggest the involvement of CYPs 1A1, 2D6 and 2C19 in the oxidative metabolism of pentamidine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pentoxifylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pentoxifylline has not been well described but some studies indicate oxidation by CYP1A2, reduction by carbonyl reductase, and oxidation by carboxylase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is demethylated by CYP3A4 and to a lesser extent by CYP2C9, and oxidated by FMO3. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Periciazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Perindopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolized to other inactive metabolites. Elimination occurs predominantly via the urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolized by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pethidine (Meperidine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolized mainly by CYP2B6 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Phencyclidine (PCP)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Phencyclidine is extensively metabolized to inactive metabolites by a variety of metabolic routes (mainly CYP3A4). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Phenelzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolized by oxidation via monoamine oxidase and to a lesser extent by acetylation.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to substantially decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by phenobarbital. The US Prescribing Information for Dovato advises to avoid coadministration due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping phenobarbital as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine.

Description:

Coadministration with phenobarbital has not been studied but a decrease in dolutegravir is expected due to induction of UGT1A1 and CYP3A enzymes. A similar reduction in exposure as observed with carbamazepine is expected. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with phenobarbital . As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with phenobarbital (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenprocoumon is metabolized by CYP2C9 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to substantially decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by phenytoin. The US Prescribing Information advises to avoid coadministration due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping phenytoin as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine.

Description:

Coadministration with phenytoin has not been studied but a decrease in dolutegravir is expected due to induction of UGT1A1 and CYP3A enzymes. A similar reduction in exposure as observed with carbamazepine is expected. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with phenytoin. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with phenytoin (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Phytomenadione (Vitamin K) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Metabolism of phytomenadione is thought to involve CYP4F2 and glucuronidation. Renal elimination of phytomenadione is minimal, therefore, there is little potential for an interaction with lamivudine via competition for renal elimination pathways. There is little potential for an interaction with dolutegravir and phytomenadione itself via competition for glucuronidation pathways as glucuronidation is not the sole route of elimination. However, phytomenadione administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pilocarpine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when pilocarpine is used either orally or as eye drops. Pilocarpine is primarily metabolized by CYP2A6 and serum esterases. Renal elimination of unchanged pilocarpine is minimal. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is metabolized mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pindolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolized to hydroxymetabolites (possibly by CYP2D6) and partly eliminated unchanged in the urine. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolized by mainly CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Piperacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Piperacillin is eliminated renally via glomerular filtration and active renal secretion by OAT1/3. Dolutegravir is not expected to inhibit OATs and lamivudine is eliminated by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Piperaquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piperaquine is mainly metabolized by CYP3A4 and is a modest inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Piroxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolized by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Dolutegravir is not expected to inhibit or induce UGT or CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Poppers (Amyl nitrate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Amyl nitrate is metabolized rapidly by hydrolytic denitration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Posaconazole is eliminated mainly unchanged in the faeces and only a minimal amount undergoes biotransformation (mainly glucuronidation by UGT1A4). Posaconazole is a strong inhibitor of CYP3A4. A clinically significant interaction is not expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as potassium is eliminated renally.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Pramipexole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pramipexole is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase pramipexole exposure. Pramipexole may compete with lamivudine for renal elimination transport mechanisms which may lead to increased concentrations of either drug. No a priori dosage adjustment of pramipexole is required unless if the patient presents pramipexole related side effects.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prasugrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pravastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Praziquantel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Praziquantel is predominantly metabolised via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Renal excretion of unchanged praziquantel appears to be minimal and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin undergoes extensive hepatic metabolism primarily by demethylation and conjugation.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prednisolone

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. When prednisone (more than 80% of which is converted to prednisolone by first pass hepatic metabolism) was coadministered with dolutegravir there was no clinically significant effect on the pharmacokinetics of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prednisone

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of prednisone (60 mg once daily with taper) and dolutegravir (50 mg once daily) had no clinically significant effect on the pharmacokinetics of dolutegravir (Cmax, AUC and Ctrough increased by 6%, 11% and 17%, respectively). No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and prednisone increased dolutegravir AUC, Cmax and Cmin by 11%, 6% and 17%, respectively. No dosage adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of prednisone (60 mg once daily with taper) and dolutegravir (50 mg once daily) increased dolutegravir Cmax, AUC and Ctrough by 6%, 11% and 17%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pregabalin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pregabalin is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Primaquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Primaquine is metabolised mainly through a non-CYP mediated mechanism and only a small fraction of the drug is believed to be metabolised through CYP450. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Primidone

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to substantially decrease dolutegravir exposure. Primidone is metabolised by CYP3A4 to the active metabolite phenobarbital which is an inducer of CPY3A4 and UGT1A1. The US Prescribing Information for Dovato advises to avoid coadministration with phenobarbital due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken with phenobarbital. This dose adjustment should be maintained for approximately 2 weeks after stopping primidone as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Probenecid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. In vitro data suggest that probenecid is a non-selective inhibitor of UGT and coadministration could increase dolutegravir concentrations, but this is unlikely to be of clinical significance. However, probenecid is an inhibitor of tubular secretion and coadministration is likely to increase lamivudine concentrations.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Procarbazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Procarbazine is metabolized to azoprocarbazine by CYP450 (mainly CYP2B and 1A) and monoamine oxidase. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Proguanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Proguanil is partly excreted unchanged and partly metabolized to its more active metabolite cycloguanil by CYP2C19 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolized mainly by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Propofol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propofol is glucuronidated via UGT1A9, UGT1A8 and is oxidized mainly via CYP2B6. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolized by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Propylthiouracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propylthiouracil is extensively metabolised, predominantly via glucuronidation, but the exact glucuronidation pathways are unknown. Renal elimination of unchanged propylthiouracil is minor. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Protamine sulphate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of protamine has not been fully elucidated, however protamine complexed with heparin is thought to be partially metabolised by fibrinolysin.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pyrantel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrantel is metabolized by CYP2D6 in vitro, however, absorption of an oral dose is minimal and over 50% of a dose is excreted unchanged in the faeces. Renal excretion of unchanged pyrantel is minimal (<7%) and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pyrazinamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolized by xanthine oxidase.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Pyridostigmine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pyridostigmine is predominantly excreted unchanged via the kidneys, with up to 74% of renal clearance attributed to active tubular secretion (most likely by a cation transporter). In vitro data indicate that dolutegravir inhibits OCT2 and could potentially increase pyridostigmine concentrations. There is also potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. The clinical relevance is unknown.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Pyridoxine (Vitamin B6) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pyridoxine is absorbed from the GI tract and is converted to the active form pyridoxal phosphate. It is excreted in the urine as 4-pyridoxic acid. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and pyridoxine itself. However, pyridoxine administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Pyrimethamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No interaction is expected with dolutegravir but in vitro data suggest that pyrimethamine inhibits the renal transporters OCT2 and MATE1 and may increase concentrations of lamivudine. No a priori dosage adjustment is recommended in patients with normal renal function.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Quercetin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inconsistencies in the literature regarding the ability of quercetin to modulate CYP/P-gp activities make it difficult to predict the nature and magnitude of any interaction. However, quercetin is unlikely to produce a large effect on dolutegravir pharmacokinetics as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Quetiapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is metabolized mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Quinapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinapril is de-esterified to the active metabolite quinaprilat which is eliminated primarily by renal excretion via OAT3. Dolutegravir is not expected to inhibit OATs. Lamivudine is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinidine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Quinine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinine is extensively metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolized by CYP2C19 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Raltegravir (RAL)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir and dolutegravir) is unlikely to be of clinical benefit.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ramipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Dolutegravir is not expected to interfere with these metabolic pathways. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Ranitidine is excreted via the kidney, partially by the cationic system. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction was observed with lamivudine.

Description:

Coadministration has not been studied but a clinically significant interaction is unlikely. No dosage adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranolazine is primarily metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rasagiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Rasagiline is metabolised predominantly by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Reboxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Red yeast rice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Red yeast rice contains monacolin K, a natural component with the same chemical structure as lovastatin. Monacolin K is metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and no interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Repaglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolized by CYPs 2C8 and 3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Retinol (Vitamin A) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and retinol itself. However, retinol administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ribavirin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ribavirin is partly metabolized (non CYP mediated) and partly excreted in the urine. Based on metabolism and clearance a pharmacokinetic interaction is unlikely with dolutegravir and no pharmacokinetic interaction was observed with lamivudine.

Description:

Coadministration with ribavirin has not been studied but a clinically significant interaction is unlikely. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

No clinically significant differences in the pharmacokinetics of lamivudine were observed when coadministered with ribavirin.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The effect of ribavirin (800 mg/day) on the plasma and intracellular PK of zidovudine, lamivudine and stavudine was studied in HIV/HCV co-infected subjects receiving zidovudine plus lamivudine, or stavudine plus lamivudine. Plasma zidovudine, lamivudine and stavudine and intracellular drug and endogenous triphosphates were measured at baseline without ribavirin and after 8-12 weeks of ribavirin co-administration. Plasma results showed no impact of ribavirin on nucleoside concentrations and ribavirin levels were consistent with previous data measured in the absence of the three NRTIs. Similar findings were observed for the deoxycytidine and deoxythymidine triphosphate analogues, when given with or without ribavirin, suggesting that ribavirin does not perturb the intracellular metabolism of zidovudine, lamivudine or stavudine.

Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with HCV/HIV co-infection: final results of a randomized clinical study. Gries JM, et al. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, February 2004, abstract 136LB.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Riboflavin (Vitamin B2) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and riboflavin itself. However, riboflavin can be found in multivitamin preparations; simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifabutin is mainly metabolized by CYP3A4 and cholinesterase. Coadministration of rifabutin (300 mg once daily) and dolutegravir alone (50 mg once daily) had no clinically significant effect on the pharmacokinetics of dolutegravir (Cmax increased by 16%; AUC and Ctrough decreased by 5% and 30%). No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and rifabutin decreased dolutegravir AUC and Cmin by 5% and 30%, due to induction of UGT1A1 and CYP3A enzymes; Cmax increased by 16%. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of rifabutin (300 mg once daily) and dolutegravir (50 mg once daily) increased dolutegravir Cmax by 16%, but decreased AUC and Ctrough by 5% and 30%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir alone (50 mg once daily) and with rifabutin (300 mg once daily) was evaluated in 9 HIV-negative subjects. Rifabutin decreased dolutegravir AUC by 5% and Ctrough by 30%, but increased Cmax by 15%. The decrease in dolutegravir Ctrough is unlikely to be clinically significant given the known PK/PD relationships and data from phase 2b dose ranging studies.

Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. Dooley KE, Sayre P, Borland J, et al. J Acquir Immune Defic Syndr, 2013, 62(1): 21-27.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Rifampicin

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with certain drugs, such as rifampicin, that may decrease dolutegravir concentrations. The European and US product labels for Dovato recommend that an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping rifampicin as the inducing effect may persist after discontinuation of a strong inducer. Coadministration of rifampicin (600 mg once daily) and twice daily dolutegravir (50 mg twice daily) decreased dolutegravir Cmax, AUC and Ctrough by 43%, 54% and 72%, respectively, compared to twice daily dolutegravir alone. When coadministration of these doses was compared to once daily dolutegravir (50 mg once daily), dolutegravir Cmax, AUC and Ctrough increased by 18%, 33% and 22%, respectively. A modelling study showed that this dose adjustment is also sufficient in individuals with a high BMI. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. Further studies are required as to whether administering dolutegravir once daily at a dose of 100 mg can mitigate the reduction in dolutegravir exposure seen with rifampicin. The interaction between lamivudine and rifampicin is unlikely to be of clinical significance. Estimated population pharmacokinetic parameters for lamivudine during and after rifampicin were similar once between-occasional variability in bioavailability and absorption rate constant were accounted for. Of note: a high dose of rifampicin (35 mg/kg) compared to the standard dose (10 mg/kg) resulted in 43% decrease in dolutegravir trough concentrations (0.46 mg/L vs 0.80 mg/L). Most patients had dolutegravir concentrations above the IC90 target (0.064 mg/L), however, a higher proportion of participants on higher dose rifampicin failed to attain the 0.3 mg/L target. Importantly, no patient below either target thresholds had a detectable HIV viral load at week 24.

Description:

Coadministration of dolutegravir and rifampicin decreased dolutegravir AUC, Cmax and Cmin by 54%, 43% and 72%, respectively, due to induction of UGT1A1 and CYP3A enzymes. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with rifampicin. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the rifampicin co-administration (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered certain drugs that may decrease dolutegravir concentrations. An additional dolutegravir 50-mg tablet, separated by 12 hours from Dovato, should be taken. Coadministration of rifampin (600 mg once daily) and dolutegravir (50 mg twice daily) decreased dolutegravir Cmax, AUC and Ctrough by 43%, 54% and 72%, respectively, when compared to dolutegravir 50 mg twice daily alone. When compared to once daily dolutegravir (50 mg once daily), dolutegravir Cmax, AUC and Ctrough increased by 18%, 33% and 22%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The effect of a higher dose of rifampicin (35 mg/kg) on the pharmacokinetics of dolutegravir or efavirenz was evaluated in coinfected HIV/TB adults. Newly-diagnosed TB patients were randomized to either a standard (10 mg/kg) or a higher (35 mg/kg) dose of rifampicin. Antiretroviral treatment naïve patients were assigned to dolutegravir or efavirenz based regimens. Patients on dolutegravir or efavirenz based regimens at enrolment were maintained on the same regimen, however, dolutegravir was adjusted from once daily to twice daily dosing. Pharmacokinetic sampling was performed 6 weeks post TB treatment initiation with sampling for dolutegravir 12 hours (Ctrough) after the last dose and a mid-dose sampling for efavirenz. Overall, 149 participants were enrolled in the study. Geometric mean (95% CI) dolutegravir trough concentration for patients on higher dose rifampicin was lower than for those receiving standard dose rifampicin: 0.46 (0.31-0.67) mg/L versus 0.80 (0.56-1.14) mg/L, with a GMR of 0.57 (0.34-0.97). Using a threshold of 0.3 mg/L, a higher proportion of participants on higher dose rifampicin failed to attain the target dolutegravir through concentration compared to those on standard dose (39% vs 7%), P = 0.014. Using a lower target threshold of 0.064 mg/L, the difference in target attainment between higher and standard dose rifampicin was not statistically significant (4.4% vs 3.6%), P = 0.999. No patients with dolutegravir concentrations below either target thresholds had a detectable HIV viral load at week 24. The geometric mean for efavirenz mid-dose concentrations for patients on higher dose rifampicin was 37% lower than those receiving the standard dose: 2.94 (95% CI, 1.98-4.36) mg/L vs 4.64 (3.31-6.50) mg/L, with a GMR of 0.63 (0.38-1.07), P = 0.083. The proportion of patients who failed to attain the target mid-dose efavirenz concentrations of 1 mg/L was not significantly different between the 2 groups. No patients below the target had a detectable HIV viral load at week 24. Grade 3-4 adverse effects were similar in the high vs standard dose rifampicin arms. Sputum conversion at week 8 was higher in high dose versus standard dose arms. In conclusion, compared to the standard dose, a three-fold dose increase for rifampicin reduced plasma exposure of dolutegravir and efavirenz without loss of virological control of HIV.

Decreased dolutegravir and efavirenz concentrations with preserved virological suppression in patients with tuberculosis and human immunodeficiency virus receiving high-dose rifampicin. Sekaggya-Wiltshire C, Nabisere R, Musaazi J, et al. Clinical Infectious Diseases 2022 [epub ahead of print].

Obesity can impact drug pharmacokinetics and consequently the magnitude of drug-drug interactions and the related recommendations for dose adjustment. Virtual clinical drug-drug interaction studies were conducted using physiologically modelling to compare the magnitude of the drug interaction between dolutegravir (50 mg twice daily) and rifampicin (600 mg daily) in non-obese (BMI 18.5-30 kg/m2), obese (BMI 30-40 kg/m2) and morbidly obese (BMI 40-50 kg/m2) individuals. Rifampicin was predicted to decrease dolutegravir AUC by 72% in obese and by 77% in morbidly obese vs 68% in non-obese individuals; however, dolutegravir trough concentrations were reduced to a similar extent (83% and 85% vs 85%). Twice-daily dolutegravir with rifampicin resulted in trough concentrations always above the protein-adjusted 90% inhibitory concentration for all BMI groups and above the 300 ng/mL threshold in a similar proportion for all BMI groups. In conclusion, the combined effect of obesity and induction by rifampicin was predicted to further decrease dolutegravir exposure but not the minimal concentration at the end of the dosing interval. Thus, dolutegravir 50 mg twice daily with rifampicin can be used in individuals with a high BMI up to 50 kg/m2.

Impact of obesity on the drug-drug interaction between dolutegravir and rifampicin or any other strong inducers. Berton M, Bettonte M, Stader F, et al. Open Forum Infectious Diseases 2023, epub ahead of print.

This study presented the 48-week outcome of the RADIANT-TB, a phase 2b, non-comparative, randomized, double-blind, placebo-controlled trial of standard vs double dose dolutegravir in individuals with tuberculosis and on rifampicin-based therapy. Participants were randomized to receive dolutegravir/lamivudine/tenofovir and either supplemental dolutegravir or placebo continued for 2 weeks after stopping TB treatment. The outcome was the proportion of individuals with HIV-RNA <50 copies/mL at week 48, treatment emergent dolutegravir resistance and adherence assessed by tenofovir-diphosphate (TFV-DP) on dried blood spots. Overall, 108 participants were included. The proportion of individuals with virologic suppression at weeks 24 and 48 were similar between arms but lower at week 48 than at week 24 likely due to declining adherence. None of the 19 participants with study defined virological failure developed treatment emergent resistance to dolutegravir.

Standard vs double dose dolutegravir in HIV-associated tuberculosis: week 48 results. Griesel R, Zhao Y, Simmons B, et al. CROI 2023, Seattle February 19-22, abstract 110.

Tenofovir/lamivudine/dolutegravir (TLD) is the WHO-preferred first-line regimen but there are limited data on the effectiveness of TLD + 50 mg dolutegravir to overcome the interaction with rifampicin in TB/HIV co-infected individuals. 91 participants with TB/HIV co-infection were included. Of those, 75 were ART-naïve participants starting TLD + 50 mg dolutegravir after 15 days on TB treatment; 10 ART naïve participants starting TLD + 50 mg dolutegravir together with rifampicin, 5 starting TB treatment and changing to TLD + 50 mg dolutegravir after a median of 3.3 y on TLD and 1 starting rifampicin and TLD + 50 mg dolutegravir after changing from EFV/3TC/TDF. Among 89 surviving participants, 6 were lost of follow-up and a further 10 had no HIV-1 RNA result due to missed or remote visits. Thus, the virological outcome was assessed in 73, of whom 69 (95%) had HIV-1 RNA <1000 copies/mL and 68 (94%) had HIV-1 RNA <200 copies/mL. No dolutegravir resistance mutations were detected among 4 participants with HIV-1 RNA >1000 copies/mL. Concomitant rifampicin containing TB treatment and TLD + 50 mg dolutegravir was well tolerated and achieved excellent viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Effectiveness of dolutegravir in people on rifampicin-based tuberculosis treatment. Shah S, Kityo C, Hughes MD, et al. CROI 2023, Seattle February 19-22, abstract 755.

Food has been shown to increase dolutegravir concentrations in healthy volunteers by 33-66%. This study aimed to evaluate whether dolutegravir dosed at 50 mg once daily taken with food would be sufficient to compensate the rifampicin inducing effect. The pharmacokinetic study conducted in Bangkok enrolled TB/HIV coinfected adults (stable on rifampicin-containing regimen for drug-susceptible TB), to receive the fixed dose combination dolutegravir/3TC/TDF 50 mg once daily with food or the same drug combination plus an additional dose of dolutegravir 50 mg administered 12 hours later. Geometric mean ratio (GMR) of dolutegravir 50 mg once daily vs 50 mg twice daily were determined and the percent of individuals with dolutegravir Cmin above the protein adjusted IC90 (i.e. 0.064 µg/mL) calculated. Twelve and sixteen participants were enrolled in the study (i.e. dolutegravir 50 mg once daily + food) and control arm (i.e. dolutegravir 50 mg twice daily), respectively. The majority were male (86%) with a median body weight of 57.5 kg. At baseline, median CD4 was 201 cells/µL (IQR 46-304) and median HIV-RNA was 4.9 log10 copies/mL (IQR 3.6-5.6). Dolutegravir Cmax was not statistically different when comparing the study arm versus the control arm. However, dolutegravir AUC was significantly lower (46% decrease) in the study arm with a GMR (90% CI) of 0.54 (0.36-0.81). Similarly, dolutegravir Cmin was significantly lower (70% decrease) in the study arm with a GMR of 0.30 (0.26-0.36) but with 83% and 94% of the study and control arm participants having dolutegravir Cmin above the protein adjusted IC90. At week 12, 83.3% and 75% of the participants in the study and control arm had HIV-RNA <50 copies/mL, respectively. The authors highlighted that even though substantial reductions in dolutegravir Cmin were observed in presence of rifampicin when dosed once daily + food, dolutegravir Cmin levels were mostly above the protein adjusted IC90 and the majority of participants were virologically suppressed at week 12.

Efficacy and PK of dolutegravir 50 mg QD with food versus 50 mg BID with rifampicin. Ueaphongsukkit T, Gatechompol S, Sophonphan J, et al. Virtual Conference on Retroviruses and Opportunistic Infections, March 2021, Abstract 370.

This study investigated whether doubling the dolutegravir dose with a once daily dose can mitigate the reduction in dolutegravir exposure seen with rifampicin. Fourteen healthy subjects received dolutegravir (50 mg or 100 mg once daily for 7 days) alone and in combination with rifampicin (600 mg once daily). Rifampicin decreased the Cmax, AUC and C24 of dolutegravir by 35%, 57% and 86% (50 mg once daily) and by 36%, 58% and 88% (100 mg once daily). When compared to 50 mg once daily alone, doubling the dose of dolutegravir to 100 mg once daily in the presence of rifampicin increased dolutegravir Cmax by 9% and decreased AUC and C24 by 26% and 76%, respectively. Although there were substantial reductions in the dolutegravir key pharmacokinetic parameter of C24, dolutegravir concentrations when administered as 100 mg once daily with rifampicin remained above the protein binding-adjusted IC of 64 ng/ml. The authors suggest further study of this dose is required.

Pharmacokinetics of dolutegravir 100 mg once daily with rifampicin. Wang X, Cerrone M, Ferretti F et al. Int J Antimicrob Agents, 2019, pii: S0924-8579(19)30095-0.

Coadministration of twice daily dolutegravir (50 mg twice daily, with lamivudine/tenofovir 300/300 mg, once daily) was studied in 10 HIV-1/TB co-infected subjects receiving rifampicin (600 mg once daily) with isoniazid, ethambutol and pyrazinamide. Dolutegravir trough concentrations were determined after at least 4 weeks of therapy and were 1123 ng/ml (820-1746 mg; median with range). Rifampicin did not significantly impact lamivudine and tenofovir plasma concentrations. After 48 weeks of therapy, two patients had plasma viral loads >50 copies/ml and were found to have dolutegravir trough concentrations below the target of 640 ng/ml, corresponding to an inhibitory quotient of 0.1 and 5. These results suggest that dolutegravir 50 mg twice daily and rifampicin should only be used in subjects without HIV integrase resistance.

Pharmacokinetic and virological efficacy of dolutegravir (50 mg BID) containing regimen in association with rifampin in HIV-infected patients using Dried Blood Spot: ANRS-12313 NAMSAL substudy in Cameroon. Le M, Cournil A, Eymard-Duverney S, et al. 19th International Workshop on Clinical Pharmacology of Antiviral Therapy, Baltimore, May 2018, Abstract 7.

Healthy volunteers received dolutegravir 50 mg once daily for 7 days, then dolutegravir 50 mg twice daily for 7 days and then dolutegravir 50 mg twice daily together with rifampicin 600 mg once daily for 14 days. Dolutegravir 50 mg twice daily in presence of rifampicin achieved 33% increase in mean AUC and 22% increase in Ctrough compared to dolutegravir 50 mg once daily alone. The authors conclude that rifampicin containing regimens including twice daily dolutegravir may represent a new treatment option for patients who require concomitant treatment of HIV and TB.

Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. Dooley KE, Sayre P, Borland J, et al. J Acquir Immune Defic Syndr, 2013, 62(1): 21-27.

The effect of rifampicin-based TB therapy on the population pharmacokinetics of lamivudine was determined using data from 16 HIV+ subjects. The estimated population pharmacokinetic parameters during and after rifampicin were similar once between-occasional variability in bioavailability and absorption rate constant were accounted for. The interaction between lamivudine and rifampicin is unlikely to be of clinical significance.

The effect of rifampicin-based tubercular therapy on the population pharmacokinetics of lamivudine. Van der Walt J, Cohen K, McIlleron H et al. 10th International Workshop on Clinical Pharmacology of HIV Therapy, Amsterdam, April 2009, abstract P24.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Rifapentine

Quality of Evidence: Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. No significant interaction is expected with lamivudine. However, coadministration may substantially decrease dolutegravir concentrations as rifapentine has a comparable inducing effect to rifampicin. Although no dosing recommendations are provided for rifapentine, the European and US labels for Dovato recommend that an additional dolutegravir 50 mg tablet, separated by 12 hours from Dovato, should be taken with rifampicin. This dose adjustment should be maintained for approximately 2 weeks after stopping rifapentine as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. In healthy volunteers receiving weekly rifapentine and isoniazid, the addition of dolutegravir resulted in flu-like symptoms and LFT elevations in 2 out of 4 patients, leading to study termination. Intolerance was hypothesized be related to rifapentine (+/- healthy volunteer status) rather than isoniazid, since in the INSPIRING study the addition of dolutegravir to daily rifampicin and isoniazid was well tolerated in HIV-TB co-infected adults. Thus, the coadministration of dolutegravir (50 mg once daily) and rifapentine/isoniazid (900/900 mg) once weekly was evaluated again in HIV infected individuals and was well tolerated in persons living with HIV. The overall dolutegravir Ctrough decreased by 47% with once weekly isoniazid/rifapentine, but the magnitude of the decrease varied by day with decreases of 23%, 64% and 56% occurring 1 day, 2 days and 5-6 days after isoniazid/rifapentine dosing, respectively. Importantly, geometric mean Ctrough values were above 300 ng/mL at all visits over the 12 weeks of co-treatment and HIV viral load remained suppressed in all participants. The authors concluded that no dose adjustment of dolutegravir is needed when coadministered with once weekly isoniazid/rifapentine. However, dolutegravir 50 mg twice daily should be considered in individuals with suspicion of failure or blips. Close monitoring of HIV infection is also recommended when using rifapentine once weekly with a daily dose of Dovato considering the limited experience when coadministering inducers with dual antiretroviral regimens.

Description:

The effect of rifapentine/isoniazid on dolutegravir was evaluated in a prospective trial enrolling 63 Taiwanese adults with HIV on a dolutegravir containing antiretroviral therapy and treated concurrently with 3HP (i.e., rifapentine/isoniazid 900/900 mg once weekly) for latent tuberculosis. The average dolutegravir plasma concentration before 3HP was 1.58 mg/L (IQR, 1.06-2.61 mg/L) and was 0.75 mg/L (IQR, 0.39-1.22 mg/L) four weeks after starting 3HP. At 12 weeks after beginning 3HP, the average dolutegravir trough concentration was 1.12 mg/L (IQR, 0.56-2.33 mg/L). The proportion of trough concentrations above the protein adjusted IC90 (0.064 mg/L) was 100% at baseline, 98.1% at week 4, and 96.2% at week 12. After excluding nine people with HIV who did not complete 3HP treatment, the rate of virological suppression was 96.3% (52/54). Two individuals had just started antiretroviral treatment less than one month before beginning 3HP and had viral loads of 14’000 and 766 copies/mL, respectively. Three individuals were lost to follow-up after completing 3HP treatment. The rates of viral load <50 copies/mL within 6 months after completing 3HP treatment were 98% (50/51) in the per-protocol analysis and 92.1% (58/63) in the intention-to-treat analysis. One individual had a viral load of 725 copies/mL at one month after completing 3HP but he had a viral load of more than 2’000’000 copies/mL at baseline before starting 3HP. This study showed that dolutegravir trough concentrations were mostly (98.1%) above the protein adjusted 90% inhibition concentration (IC90: 0.064 mg/L) across all visits during the twelve doses of 3HP in people with HIV. In addition, the participants maintained a high rate of HIV viral suppression (98%) within 6 months after completing 3HP.

Drug monitoring was conducted for rifapentine among people with HIV receiving dolutegravir containing antiretroviral therapy and latent tuberculosis treatment. Chen JH, Lin YC, Chen CP et al. J Microbiol Immunol Infect, 2024, epub ahead of print.

Weekly isoniazid and rifapentine for 3 months (3HP) given to virally suppressed people with HIV on dolutegravir-based regimens has been found to be safe and to maintain virologic suppression with adequate dolutegravir levels. This study aimed to evaluate whether 3HP can be administered simultaneously with dolutegravir-based regimens also in ART-naive people. Participants were assigned to 6 months isoniazid (6H; n=25) and 3HP (n=50). Pharmacokinetic sampling was performed prior to the first 3HP dose, 3 days after the 3rd HP dose and 3 days after the 8th HP dose in both groups. By week 8, viral suppression (VL <50 copies/mL) was achieved in 100% participants in both groups. At week 12, viral suppression was present in 44/50 (88%) and 23/25 (92%) participants in the 3HP and 6H groups, respectively. Dolutegravir trough concentration was above the PA-IC90 (64 ng/mL) in all participants at all timepoints, and 158 ng/mL (the lower 5th percentile confidence bound of concentrations achieved with fully suppressive 10 mg daily dosing in the SPRING-1 trial) in all but 2 individuals at week 3 and in all individuals at week 8. The 2 individuals with dolutegravir <158 ng/mL at week 3 suppressed by week 8. Simultaneous initiation of 3HP and dolutegravir-based ART resulted in rapid viral suppression among ART-naive people with HIV. Despite a 72% induction of dolutegravir clearance in the 3HP group, dolutegravir concentrations enabled viral suppression < 50 copies/mL in all individuals in both groups at 8 weeks.

Simultaneous initiation in ART-naive PWH of DTG-based ART and 3HP maintains efficacious DTG levels. Weld ED, Perez Solans B, Salles I, et al. Conference on Retroviruses and Opportunistic Infections, Denver, March 2024, abstract 156.

The effect of daily rifapentine/isoniazid (600/300 mg once daily for 1 month, 1HP) on the pharmacokinetics of dolutegravir was evaluated in 32 participants receiving dolutegravir 50 mg twice while on treatment with 1HP. Dolutegravir pharmacokinetics was evaluated before 1HP treatment while dolutegravir was dosed 50 mg once daily (day 0) and during 1HP treatment while dolutegravir was dosed 50 mg twice daily (day 28). The median dolutegravir trough concentrations was 1751 ng/mL on day 0 versus 1987 on day 28. Median dolutegravir trough concentrations at days 3, 14, and 21 were 4386, 1950 and 2004, ng/mL, respectively. At the end of dosing (day 28), 31/32 participants had HIV RNA levels <50 copies/mL. One participant had an HIV viral load of 160 copies/mL at day 28 (dolutegravir concentration was 2162 ng/mL), however, repeat viral load was <50 copies/mL on day 42. No serious adverse events were reported. Dolutegravir trough concentrations with 50 mg twice daily dosing during 1HP treatment were higher than those with standard dose dolutegravir once daily alone. The pharmacokinetic, virological and safety data provide evidence for twice daily dolutegravir in combination with 1HP for TB prevention.

Twice-daily dolutegravir based antiretroviral therapy with one month of daily rifapentine and isoniazid (1HP) for TB prevention. Podany AT, Cramer Y, Imperial M, et al. Clin Infect Dis. 2024, Epub ahead of print.

Once weekly rifapentine/isoniazid doses (900/900 mg) for 3 months (3HP) coadministered with once daily dolutegravir has resulted in serious adverse events in a previous study conducted in healthy volunteers requiring the premature interruption of the study. This study evaluated the safety, drug interactions and viral suppression of dolutegravir (50 mg once daily) with once weekly 3HP in 61 HIV infected individuals. The overall dolutegravir Ctrough geometric mean ratio (GMR) with and without once weekly isoniazid/rifapentine was 0.53 (90% CI 0.49-0.56). The GMR varied by day with values of 0.77 (0.71-0.84) 1 day after isoniazid/rifapentine dosing, 0.36 (0.32-0.4) 2 days after dosing and 0.44 (0.4-0.48) 5-6 days after dosing. Importantly, geometric mean Ctrough values were above 300 ng/mL at all visits over the 12 weeks of co-treatment and HIV viral load remained suppressed in all participants. No rifapentine/isoniazid-related adverse effects above Grade 3 were observed in the study participants. The authors concluded that dolutegravir 50 mg once daily may be coadministered with a once weekly rifapentine/isoniazid treatment without dose adjustment of dolutegravir in HIV infected individuals.

Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. Dooley KE, Savic R, Gupte A et al. Lancet HIV 2020; 7(6):e401-9.

INSPIRING (NCT02178592) is a Phase 3b, non-comparative, active control, randomised, open-label study in HIV-1 infected ART-naïve adults (CD4+ ≥50 cells/µL) with drug-sensitive TB. Participants on rifampin-based TB treatment for up to 8 weeks were randomised (3:2) to receive dolutegravir (50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily) or efavirenz (600 mg once daily), with 2 investigator-selected NRTIs for 52 weeks. Of 113 subjects enrolled, 69 were randomised to dolutegravir and 44 to efavirenz. The week 48 response rates were 75% (52/69, 95% CI 65-86%) for dolutegravir and 82% (36/44, 95% CI 70-93%) for efavirenz. The dolutegravir non-responses were driven by non-treatment related discontinuations (n=10 lost to follow-up). There were no deaths or study drug switches. There were 2 discontinuations for toxicity (efavirenz). There were 3 protocol-defined virological failures (2 dolutegravir, no acquired resistance; 1 efavirenz, emergent resistance to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors). The tuberculosis treatment success rate was high. Tuberculosis-associated IRIS was uncommon (4/arm), with no discontinuations for IRIS. The authors concluded that twice-daily dolutegravir was effective and well tolerated in adults with HIV receiving rifampicin-based tuberculosis treatment.

Dolutegravir-based antiretroviral therapy for patients coinfected with tuberculosis and human immunodeficiency virus: a multicenter, noncomparative, open-label, randomized trial. Dooley KE, Kaplan R, Mwelase N, et al. Clin Infect Dis 2020;70(4):549-556.

An open-label, intrasubject drug interaction study in HIV-negative healthy volunteers comprised investigated the pharmacokinetics of dolutegravir once daily alone and with once weekly isoniazid and rifapentine. Of 4 enrolled subjects (3 males, 1 female, age 22-46 years), 3 completed the study and 1 withdrew prior to the 3rd dose of isoniazid/rifapentine. The study was stopped prematurely due to the development of multiple AEs in 2 subjects. In both subjects, flu-like syndrome with symptoms of nausea, vomiting, and fever (Grades 2 and 3) began ~8 hours after the last doses of dolutegravir, rifapentine, and isoniazid and lasted 24-48 hours. One subject required a 24-hour hospitalization for management of orthostatic hypotension (Grade 3). Transaminase elevations (Grades 2-4) occurred in both subjects. Exposure to rifapentine and its active metabolite were similar to reference PK data, but isoniazid exposure was 67-92% higher than expected in the 2 subjects who developed AEs. Limited pharmacokinetic data suggested isoniazid/rifapentine decreased dolutegravir AUC and Cmin by 46% and 74%. Given that flu-like syndrome was reported in <4% of subjects in studies of the efficacy of weekly isoniazid/rifapentine alone, these data suggest that co-administration of dolutegravir and weekly isoniazid/rifapentine should be avoided.

Early termination of a PK study between dolutegravir and weekly isoniazid/rifapentine. Brooks KM, Pau AK, George JM, et al. CROI 2017, Seattle, February 2017, abstract 409a.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rifaximin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Rilpivirine (RPV)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration of rilpivirine (25 mg once daily) and dolutegravir (50 mg once daily) increased dolutegravir Cmax, AUC and Ctrough by 13%, 12% and 22%, respectively. Rilpivirine Cmax, AUC and Ctrough increased by 10%, 6% and 21%, respectively. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir and rilpivirine increased dolutegravir AUC, Cmax and Cmin by 12%, 13% and 22%, respectively. There was no change in rilpivirine pharmacokinetics. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) and rilpivirine (25 mg once daily) was studied in 16 HIV-negative subjects. Rilpivirine increased dolutegravir AUC, Cmax and Ctrough by 12%, 13% and 22%, respectively. Similarly, rilpivirine AUC, Cmax and Ctrough increased by 6%, 10% and 21%, respectively, in the presence of dolutegravir. Dolutegravir and rilpivirine can be coadministered without dosage adjustment for either agent.

Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Ford SL, Gould E, Chen S, et al. Antimicrob Agents Chemother, 2013, 57(11):5472-7.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Rilpivirine/ Emtricitabine/Tenofovir alafenamide (RPV/FTC/TAF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) and Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine.

Description:

Odefsey is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be co-administered with other antiretroviral medicinal products. Odefsey should not be co-administered with medicinal products containing lamivudine.

Odefsey Summary of Product Characteristics, Gilead Sciences Ltd, January 2019.

Because Odefsey is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

Odefsey US Prescribing Information, Gilead Sciences Inc, October 2018.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rimantadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Dolutegravir is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Riociguat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Riociguat is metabolized by CYP1A1, CYP3A4, CYP2C8, CYP2J2 and is also eliminated unchanged in the bile and renally. Riociguat is a substrate of P-gp and BCRP. Dolutegravir and lamivudine do not interfere with riociguat metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ritonavir (RTV)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with ritonavir would be possible from a pharmacokinetic standpoint. Based on studies with boosted PIs, ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of ritonavir. No interaction is expected with lamivudine.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rituximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rituximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). In vitro data indicate that dolutegravir does not inhibit P450 isoenzymes or the efflux transporters P-gp, BCRP at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rizatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rizatriptan is metabolized by oxidative deamination by monoamine oxidase-A (MAO-A).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rocuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rocuronium is mostly cleared in the bile although up to 30% may be excreted renally. P-gp was shown to mediate biliary excretion of rocuronium in a rat model, however, in vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Roflumilast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Roflumilast is metabolized by CYP3A4 and CYP1A2 to form roflumilast N-oxide, with both roflumilast and roflumilast N-oxide having PDE4 inhibitory activity. Roflumilast N-oxide is subsequently dealkylated by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ropinirole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ropinirole is metabolised predominantly by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rosiglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolized mainly by CYP2C8 and to a lesser extent by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosuvastatin is largely excreted unchanged via the faeces.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sacubitril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sacubitril is rapidly converted to LBQ657 (active metabolite) by carboxylesterases and the active metabolite is not further metabolized to a significant extent.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Salbutamol (Albuterol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolized to the inactive salbutamol-4’-O-sulphate. No interaction is expected with dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Saw palmetto (Serenoa repens)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Selexipag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selexipag is hydrolysed to its active metabolite by carboxylesterase 1 (CES1). Both selexipag and its active metabolite undergo oxidative metabolism by CYP2C8 and CYP3A4. The active metabolite is also glucuronidated by UGT1A3 and UGT2B7. Dolutegravir and lamivudine do not interfere with selexipag metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Senna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolized by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Seville orange juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Seville orange juice inhibits intestinal CYP3A4 but is unlikely to cause a significant effect on dolutegravir exposure as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sevoflurane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as sevoflurane is almost exclusively eliminated unchanged by the lungs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sildenafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sildenafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sirolimus is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sitagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, P-gp), with metabolism by CYP3A4 representing a minor elimination pathway. Dolutegravir is not expected to inhibit these transporters at clinically relevant concentrations. Although metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal impairment or end-stage renal disease (ESRD), a clinically significant increase is unlikely as sitagliptin is mainly eliminated unchanged and has a large safety window, and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sodium nitroprusside

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. There is little or no renal elimination of unchanged drug. There is little potential for sodium nitroprusside to affect the disposition of antiretrovirals, or to be affected if coadministered with antiretrovirals.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sodium stibogluconate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elimination of sodium stibogluconate is predominantly via renal glomerular filtration. No interaction is expected with dolutegravir. Renal elimination of sodium stibogluconate has been found to be similar to the rate of glomerular filtration and there is little potential for an interaction with lamivudine via competition for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sofosbuvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 (major) and CYP3A (minor), neither of which is affected by sofosbuvir. Coadministration of sofosbuvir (400 mg once daily) and dolutegravir (50 mg once daily) decreased sofosbuvir Cmax and AUC by 12% and 8%. GS-331007 (sofosbuvir metabolite) Cmax increased by 1%, whereas AUC and Cmin both decreased by 1%. An interaction with lamivudine is unlikely as lamivudine is predominately cleared unchanged by renal excretion. Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications.

Description:

Coadministration of sofosbuvir (400 mg once daily) and dolutegravir (50 mg once daily) decreased sofosbuvir Cmax and AUC by 12% and 8%. GS-331007 (sofosbuvir metabolite) Cmax increased by 1%, whereas AUC and Cmin both decreased by 1%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sofosbuvir/Velpatasvir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Based on drug interaction studies conducted with sofosbuvir/velpatasvir, no clinically significant drug interactions have been observed with dolutegravir. Coadministration of sofosbuvir/velpatasvir (400/100 mg, once daily) and dolutegravir (50 mg once daily) had no effect on the pharmacokinetic parameters of sofosbuvir (AUC and Cmax decreased by 8% and 12%), GS-331007 (AUC and Cmin both decreased by 1%, Cmax increased by 1%), velpatasvir (AUC, Cmax and Cmin decreased by 9%, 6% and 12%) or dolutegravir (AUC, Cmax and Cmin increased by 6%, 6% and 4%) was observed. Lamivudine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir or velpatasvir.

Description:

Coadministration of dolutegravir and sofosbuvir/velpatasvir had no effect on the pharmacokinetics of dolutegravir, sofosbuvir or velpatasvir. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of velpatasvir (100 mg once daily) and dolutegravir (50 mg once daily) decreased velpatasvir Cmax, AUC and Cmin by 6%, 9% and 12%, respectively.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of sofosbuvir/velpatasvir (400/100 mg, once daily) and dolutegravir (50 mg once daily) was studied in 24 healthy volunteers in a cross-over study. Sofosbuvir AUC and Cmax decreased by 8% and 12%; AUC and Cmin of GS-331007 both decreased by 1% and Cmax increased by 1%. Velpatasvir AUC, Cmax and Cmin decreased by 9%, 6% and 12%, respectively. Dolutegravir AUC, Cmax and Cmin increased by 6%, 6% and 4%, respectively. Sofosbuvir/velpatasvir and dolutegravir-containing regimens may be coadministered without dose adjustment.

Drug-drug interaction studies between Hepatitis C Virus antivirals sofosbuvir/velpatasvir and boosted and unboosted Human Immunodeficiency Virus antiretroviral regimens in healthy volunteers. Mogalian E, Stamm L, Osinusi A, et al. Clin Infect Dis, 2018, 67(6): 934-940.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sofosbuvir/Velpatasvir/Voxilaprevir

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No clinically significant drug interactions have been observed with dolutegravir and sofosbuvir/velpatasvir and no additional effect is likely with the addition of voxilaprevir. Lamivudine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir, velpatasvir or voxilaprevir.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Solifenacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Solifenacin is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sorafenib is metabolized to a moderate extent by CYP3A4 and UGT1A9, UGT1A1. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Sorafenib inhibits UGT1A1 and UGT1A9 and therefore could potentially increase dolutegravir concentrations, however, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Spectinomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spectinomycin is predominantly eliminated unchanged by the kidneys via glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Spironolactone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spironolactone is partly metabolized by the flavin containing monooxygenases.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Stanozolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol is extensively hydroxylated and conjugated followed by renal excretion. Dolutegravir and lamivudine do not affect these pathways.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to decreased dolutegravir exposure. The US Prescribing Information for Dovato advises to avoid coadministration due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping St John’s wort as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine. A recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp).

Description:

Coadministration has not been studied but a decrease in dolutegravir is expected due to induction of UGT1A1 and CYP3A enzymes. A similar reduction in exposure as observed with carbamazepine is expected. The recommended dose of dolutegravir is 50 mg twice daily when co-administered with St. John's wort. As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the St. John's wort co-administration (a separate formulation of dolutegravir is available for this dose adjustment).

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

In a phase I, open-label, non-randomized, single-sequence study, a low-hyperforin St John’s wort extract was investigated using a drug cocktail in 20 healthy volunteers. No pharmacokinetic interactions were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein, with AUC and Cmax of the probe drugs showing 90% confidence intervals well within the predefined bioequivalence range of 80-125% (GMR, drugs taken together with extract vs. probe drug alone). These data suggest that low hyperforin preparations of St John’s wort have a lower risk of drug-drug interactions than high hyperforin St. John’s wort preparations.

No clinically relevant interactions of St. John's Wort extract Ze 117 low in hyperforin with cytochrome P450 enzymes and P-glycoprotein. Zahner C, Kruttschnitt E, Uricher J, et al. Clin Pharmacol Ther, 2019, 106(2): 432-440.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Streptokinase

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Renal elimination of unchanged streptokinase is minimal. No interaction is expected with dolutegravir and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Streptomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is excreted rapidly in the urine by glomerular filtration.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Strontium ranelate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. A pharmacokinetic interaction with lamivudine is unlikely as strontium is predominantly eliminated unchanged by the kidneys. However, strontium is a divalent cation and can chelate with dolutegravir thereby reducing its absorption. Separating administration of dolutegravir/lamivudine and strontium ranelate by at least 4 hours is recommended.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sufentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sufentanil undergoes extensive CYP3A4 metabolism, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Sulfadiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sulfadiazine is metabolized in part by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Sulfadiazine has been associated with crystalluria leading to renal toxicity and in some cases renal failure, and case reports in immunocompromised patients have suggested that AIDS patients may be particularly prone to sulfadiazine-induced renal toxicity. As lamivudine is predominantly excreted via active renal transport, monitoring of renal function is warranted if sulfadiazine is administered with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Sulfadoxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sulfadoxine is rarely used alone, but is usually given in combination with pyrimethamine. No interaction is expected with dolutegravir, however, in vitro data suggest that pyrimethamine inhibits the renal transporters OCT2 and MATE1 and may increase concentrations of lamivudine. No a priori dosage adjustment is recommended in patients with normal renal function.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sulfasalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Multiple mechanisms are thought to be involved in sulfasalazine metabolism including acetylation, hydroxylation, and glucuronidation. Renal elimination of unchanged sulfasalazine is minimal. There is, therefore, low potential for clinically significant interactions with dolutegravir or with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sulpiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as sulpiride is mainly excreted in the urine and faeces as unchanged drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sumatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sumatriptan is eliminated primarily by monoamine oxidase A-mediated metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sunitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sunitinib is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Suramin sodium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Suramin appears to be eliminated predominantly unchanged via renal glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction with lamivudine via competition for renal transport pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Suxamethonium (Succinylcholine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Suxamethonium is hydrolysed by plasma cholinesterase and there is little potential for an interaction with dolutegravir via modulation of or competition for metabolic pathways. Renal elimination of unchanged suxamethonium is minimal and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tacrolimus is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tadalafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tadalafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tamoxifen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolic profiles of the drugs there is little potential for pharmacokinetic interaction. Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tamsulosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tapentadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tapentadol is mainly glucuronidated by UGT1A6, UGT1A9 and UGT2B7 and does not induce or inhibit CYP450 enzymes in the range of doses in clinical use. Dolutegravir is glucuronidated by other UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tazobactam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is only minimally metabolised and is eliminated renally via glomerular filtration and active renal secretion by OAT1/3. Dolutegravir is not expected to inhibit OATs and lamivudine is eliminated by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Telbivudine

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telbivudine is eliminated primarily by urinary excretion as unchanged drug. The renal clearance of telbivudine approaches normal glomerular filtration rate, suggesting that filtration is the main mechanism of excretion. No interaction is expected with dolutegravir. Coadministration of telbivudine (200 mg once daily) and lamivudine (100 mg once daily) to 16 subjects had no significant effect on telbivudine Cmax and AUC (both increased by ~6%) or lamivudine Cmax and AUC (decreased by 14% and 1%). Although doses studied were lower than used in clinical practice, no interaction is expected at clinically relevant doses.

Description:

Coadministration of telbivudine (200 mg once daily) with lamivudine (100 mg once daily) was studied in 16 healthy men. Telbivudine Cmax and AUC increased by 6.7% and 6.3%; lamivudine Cmax and AUC decreased by 14% and 1%. Although the doses studied were lower than used in clinical practice, a clinically significant interaction is unlikely at higher doses.

Pharmacokinetics of telbivudine in healthy subjects and absence of drug interaction with lamivudine or adefovir dipivoxil. Zhou X, Fielman B, Lloyd D, et al. Antimicrob Agents Chemother, 2006, 50(7): 2309-2315.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telithromycin is metabolized by CYP3A4. Dolutegravir does not affect CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Telmisartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Dolutegravir undergoes glucuronidation mainly via UGT1A1 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Temazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated, but there is no evidence that temazepam is a substrate of UGT1A1, the major enzyme involved in dolutegravir metabolism. Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Temsirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temsirolimus is metabolized by CYP3A4 and inhibits CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tenofovir alafenamide (HBV)

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Coadministration of tenofovir alafenamide (10 mg once daily, with emtricitabine) and dolutegravir (50 mg once daily) increased dolutegravir Cmax, AUC and Cmin by 15%, 2% and 5%, respectively. Tenofovir alafenamide Cmax and AUC increased by 24% and 19%; tenofovir Cmax and AUC increased by 10% and 25%. No interaction is expected with lamivudine.

Description:

Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) was studied in 10 healthy volunteers in a crossover study. Tenofovir alafenamide AUC and Cmax increased by 17% and 24%, respectively. Tenofovir AUC and Cmax increased by 25% and 10%, respectively. Dolutegravir pharmacokinetic parameters were similar to historical controls.

Pharmacokinetics of tenofovir alafenamide when coadministered with other HIV antiretrovirals. Begley R, Das M, Zhong L, et al. J Acquir Immune Defic Syndr, 2018, 78(4): 465-472.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Tenofovir-DF (TDF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with tenofovir-DF would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with tenofovir. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir or lamivudine. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. Coadministration of tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) had no effect on AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax.

Description:

Coadministration of dolutegravir and tenofovir increased dolutegravir AUC by 1% and decreased Cmax and Cmin by 3% and 8%. There was no change in tenofovir pharmacokinetics. No dose adjustment is necessary when Dovato is combined with tenofovir.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended. No clinically significant differences in the pharmacokinetics of tenofovir (organic anion transporter [OAT]1 and OAT3 substrates) were observed when coadministered with dolutegravir.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (50 mg once daily) and tenofovir-DF (300 mg once daily) was studied in 15 HIV-negative subjects. The pharmacokinetic parameters of tenofovir and dolutegravir when coadministered were comparable to those when given alone, demonstrating no significant drug interaction. Dolutegravir AUC increased by 1%, but Cmax and Ctrough decreased by 3% and 8%, respectively. Tenofovir AUC, Cmax and Ctrough increased by 12%, 9% and 19%, respectively.

Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects. Song I, Min SS, Borland J, et al. J AIDS, 2010, 55(3): 365-367.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Terazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terazosin is extensively metabolized in the liver possibly via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolized by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and 2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Terfenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terfenadine undergoes extensive metabolism mainly by CYP3A4 to form azacyclonol and terfenadine alcohol. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tetracaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Absorbed tetracaine is predominantly metabolised by pseudocholinesterases in the plasma.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tetracyclines

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracyclines are eliminated unchanged primarily by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Thalidomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as thalidomide is cleared by non-enzymatic hydrolysis.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Theophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolized by CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Thiamine (Vitamin B1) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and thiamine itself. However, thiamine can be found in multivitamin preparations; simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Thiopental

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although pentobarbital (a potent inducer of hepatic microsomal drug metabolism) is formed during thiopental metabolism, levels do not reach the therapeutic range. Therefore, dolutegravir pharmacokinetics are unlikely to be affected significantly by coadministration with thiopental. Renal excretion of unchanged thiopental is thought to be minimal so there is little potential for an interaction with lamivudine due to competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Thioridazine is metabolized by CYP2D6 and to a lesser extent by CYP3A4. No effect on thioridazine is expected as dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Thioridazine is a moderate inducer of CYP3A4 and could potentially decrease dolutegravir concentrations, but this is unlikely to be of clinical significance as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tiagabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiagabine is metabolised by CYP3A4/5. Neither dolutegravir nor tiagabine induce or inhibit CYP450 enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tiapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tiapride is excreted largely unchanged in the urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ticagrelor undergoes extensive CYP3A4 metabolism and is only a mild inhibitor of CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Timolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when timolol is used either orally or as eye drops. Timolol is predominantly metabolised by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tinidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinidazole is partly metabolized by CYP3A4, but dolutegravir and lamivudine do not inhibit or induce CYP450 enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tiotropium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiotropium bromide is predominantly excreted unchanged in the urine. Metabolism by CYP2D6 and CYP3A4 is only a minor role in its elimination. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tizanidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Tizanidine is metabolised by CYP1A2 which is not inhibited or induced by dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolized by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 having a major role in CYP2D6 poor metabolisers. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Topiramate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topiramate is mainly eliminated by renal elimination in unchanged form (up to 60% of the dose) and partly by oxidation. Weak induction of CYP isozymes has been observed with higher doses of topiramate but this is not considered to be of clinical relevance with dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Topotecan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topotecan undergoes both hepatic and renal elimination. Hepatic elimination involves mainly non-enzymatic hydrolysis and, to a minor extent, CYP mediated N-demethylation as well as glucuronidation. Renal elimination is by both active secretion (mainly via OAT3) and glomerular filtration. Topotecan is a substrate for P-gp and BCRP and concomitant use of P-gp and BCRP inhibitors has been shown to increase topotecan exposure. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Torasemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolized mainly by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Toremifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Toremifene is mainly metabolized by CYP3A4 to N-demethyltoremifene. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolized by CYPs 3A4, 2B6, and 2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trandolapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as trandolapril is hydrolysed to trandolaprilat.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tranexamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tranexamic acid is mainly cleared by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tranylcypromine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tranylcypromine is hydroxylated and acetylated.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trazodone is primarily metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Treprostinil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Treprostinil is mainly metabolized by CYP2C8 and to a lesser extent by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Triamcinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamcinolone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Triazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Triclabendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. In vitro data suggest that, triclabendazole and its active sulfoxide metabolite are inhibitors of CYP3A4. Coadministration may increase dolutegravir concentrations although to a moderate extent as CYP3A4 does not play a major role in dolutegravir metabolism. Furthermore, due to short term dosing of triclabendazole, the effect on antiretrovirals is likely to be minimal. Renal excretion of unchanged triclabendazole appears to be minimal (<10%) and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Trimethoprim/Sulfamethoxazole

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/lamivudine has not been studied. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with trimethoprim and sulfamethoxazole. In vitro data indicate that trimethoprim inhibits the renal transporters OCT2 and MATE1. Coadministration with trimethoprim increased lamivudine exposure by 43%, but lamivudine had no effect on trimethoprim or sulfamethoxazole. Note, the bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such trimethoprim/sulfamethoxazole paediatric suspension.

Description:

Coadministration of trimethoprim/sulfamethoxazole (160 mg/800 mg once daily for 5 days) and lamivudine (300 mg single dose) increased lamivudine AUC and Cmax by 43% and 7%, due to OCT inhibition. Trimethoprim and sulfamethoxazole AUCs were unchanged. No dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

No clinically significant differences in the pharmacokinetics of trimethoprim/sulfamethoxazole or lamivudine were observed when coadministered.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Non-linear mixed effects modelling analysis on samples from 77 HIV-infected subjects receiving lamivudine alone (150 twice daily) or with nevirapine (200 mg twice daily) with concurrent trimethoprim/sulfamethoxazole (160/800 mg every other day [n=51], three times weekly [n=23], or twice daily [n=3]) revealed an effect of trimethoprim/sulfamethoxazole on lamivudine pharmacokinetics. There was a significant reduction of 31% in apparent oral clearance of lamivudine which would be expected to result in a 43% increase in the average steady-state concentration.

Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection. Sabo JP et al. AAPS Pharm Sci, 2002, 2: E1.

The effect of trimethoprim/sulfamethoxazole (160/800 mg once daily) on a single dose of lamivudine (300 mg) was studied in 14 HIV-infected subjects. Coadministration increased lamivudine AUV by 43% and decreased renal clearance by 35%. There was no effect of lamivudine on the pharmacokinetics of trimethoprim of sulfamethoxazole. Given the favourable safety profile of lamivudine, it is unlikely that this interaction will result in a significant increase in concentration-related toxicity at the doses studied.

Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole. Moore KHP, et al. Clin Pharmacol Ther, 1996, 59: 550-558.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.

Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trimipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolized mainly by CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Triptorelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triptorelin metabolism in humans is unknown but possibly involves degradation by peptidases.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Trospium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Trospium is minimally metabolized and is mainly eliminated unchanged renally, in part by OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase trospium exposure, but the clinical relevance of this is unknown. Trospium could potentially compete with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Turmeric (Curcuma longa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect is expected on dolutegravir as curcumin and/or turmeric extracts had no significant effect on the pharmacokinetics of probe drugs for various UGT enzymes. Although curcumin inhibits BCRP, a clinically relevant effect on dolutegravir is unlikely. No effect on lamivudine is expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ulipristal is metabolized mainly by CY3A4 and to a lesser extent by CYPs 1A2 and 2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Umeclidinium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Umeclidinium bromide is mainly metabolized by CYP2D6 and is a substrate of P-gp. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ursodeoxycholic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Ursodeoxycholic acid is conjugated with glycine or taurine in the liver and secreted into bile. In vitro studies suggest that ursodeoxycholic acid is a CYP3A inducer. No significant effect on dolutegravir is expected as it does not undergo major metabolism by CYP3A4 and there is no evidence that ursodeoxycholic acid induces UGT1A1. No effect is expected on lamivudine as it is not metabolized by CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valaciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valaciclovir is converted to aciclovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Dolutegravir is not expected to inhibit this renal transporter and lamivudine is eliminated by different transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valerian

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as valsartan is eliminated unchanged mostly through biliary excretion.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vancomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vancomycin is excreted unchanged via renal glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine for active renal transport mechanisms.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vardenafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vardenafil is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Varenicline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Varenicline is eliminated unchanged by the kidneys via glomerular filtration and active tubular secretion by OCT2. No interaction is expected with dolutegravir (via inhibition of OCT2) or lamivudine (via competition for active renal transport mechanisms as cimetidine (an inhibitor of renal transporters) was shown to increase varenicline exposure to a limited extent (29%).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vecuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vecuronium is partly deacetylated and partly cleared in the bile as parent compound.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolized by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Verapamil is metabolised mainly by CYP3A4 and is a moderate inhibitor of CYP3A4. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vigabatrin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vigabatrin is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vilanterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vilanterol is metabolized by CYP3A4 and is a substrate of P-gp. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vildagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vildagliptin is inactivated via non-CYP mediated hydrolysis.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vinblastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vinblastine is metabolized by CYP3A4, but dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Vinblastine induces CYP3A4 but no significant effect is expected on dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

Midazolam pharmacokinetics was evaluated in 6 patients who were enrolled in a phase I/II study of infusional vinblastine given in combination with the P-glycoprotein antagonist valspodar and received the CYP3A4 probe drug midazolam. Vinblastine increased the median clearance of the CYP3A4 probe drug midazolam from 21.7 L/h to 32.3 L/h. In vitro, vinblastine induced CYP3A4 protein. Cell-based reported gene assays using transiently transfected HepG2 and NIH3T3 cells indicated that vinblastine weakly activated human and mouse full-length NR1I2 but had no effect on NR1I3. Collectively, these findings suggest that vinblastine is able to induce CYP3A and thus has the potential to cause interactions with other CYP3A4 substrates.

Induction of CYP3A4 by vinblastine: role of the nuclear receptor NR1I2. Smith NF, Mani S, Schuetz EG, et al. Ann Pharmacother. 2010; 44(11):1709-17.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vincristine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vincristine is metabolized by CYP3A5/4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vinorelbine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vinorelbine is metabolized by CYP3A4, but dolutegravir and lamivudine do not inhibit or induce CYP450 enzymes.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Tocopherol (Vitamin E) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and vitamin E itself. However, vitamin E can be found in multivitamin preparations; simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Voriconazole is metabolised by CYPs 2C19, 2C9 and 3A4 and is a strong inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism and dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vorinostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Vorinostat is mainly metabolised by glucuronidation (UGT2B17) and hydrolysis followed by B oxidation (non CYP-mediated). Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vortioxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vortioxetine is mainly metabolized by CYP2D6 and to a lesser extent CYP2C9 and CYP3A4/5. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Warfarin is a mixture of enantiomers which are metabolized by different cytochromes. R-warfarin is primarily metabolized by CYP1A2 and 3A4. S-warfarin (more potent) is metabolized by CYP2C9. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Xipamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 90% of xipamide is excreted in the urine, mainly as unchanged drug (50%) and glucuronides (30%).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolized by aldehyde oxidase and to a lesser extent CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zanamivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small amount of the orally inhaled zanamivir is systemically absorbed. Absorbed zanamivir is excreted unchanged in the urine whereas unabsorbed zanamivir is excreted in the faeces.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Zidovudine (AZT, ZDV)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with zidovudine would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with zidovudine. No interaction is expected with dolutegravir. No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed with coadministration of zidovudine (200 mg, single dose) and lamivudine (300 mg single dose).

Description:

Coadministration with zidovudine has not been studied, but no dose adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

The pharmacokinetics and safety of single doses of abacavir (600 mg), zidovudine (300 mg) and lamivudine (150 mg) were evaluated when given alone or with either or both of the other drugs to 13 HIV-infected subjects. Coadministration of abacavir with zidovudine (with or without lamivudine) decreased ZDV Cmax by ~20%, delayed ZDV Tmax by 0.5h and increased AUC of zidovudine glucuronide by up to 40%. There were no differences in the pharmacokinetics of abacavir when given alone, or with zidovudine or lamivudine, or with both zidovudine and lamivudine.

Single dose pharmacokinetics and safety of abacavir (1592U98), zidovudine, and lamivudine administered alone and in combination in adults with human immunodeficiency virus infection. Wang LH, et al. Antimicrob Agents Chemother, 1999, 43: 1708-1715.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ziprasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zoledronic acid (Zoledronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Zoledronic acid is eliminated unchanged renally. (Note, caution is required if given with calcium supplements as dolutegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced dolutegravir concentrations.)

Description:

Coadministration of calcium supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 39%, 37% and 39%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing calcium can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. When taken with food, Dovato and supplements containing calcium can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=12) decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir (n=11) had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. Dolutegravir and calcium supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zolmitriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolmitriptan is metabolized by CYP1A2 and the N-demethylated metabolite (active) undergoes further metabolism by MAO-A. In vitro data indicate that zolmitriptan is a substrate of P-glycoprotein. Dolutegravir does not inhibit or induce CYP1A2 or P-glycoprotein. Zolmitriptan does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9 and CYP1A2. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zonisamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zonisamide is metabolized partly by CYP3A4 and also by N-acetyl-transferases and conjugation. Zonisamide is a weak inhibitor of P-gp but is unlikely to have a significant effect on dolutegravir exposure. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zopiclone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zotepine is mainly metabolized by CYP3A4 and to a lesser extent CYP1A2 and CYP2D6. Dolutegravir undergoes only minimal metabolism via CYP3A4 and does not inhibit or induce CYPs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolized by sulphoxidation, N-dealkylation (by CYP2D6 and CYP3A4) and glucuronidation. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Conjugated estrogens

Quality of Evidence: Very Low

Summary:

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Dolutegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with progestogens administered as part of HRT. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Brigatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brigatinib is metabolised by CYP2C8 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Brigatinib is a weak inhibitor of CYP3A4 but is unlikely to cause a clinically significant increase in dolutegravir exposure. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Drospirenone (POP)

Quality of Evidence: Very Low

Summary:

Coadministration with a drospirenone progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Medroxyprogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Midazolam (buccal)

Quality of Evidence: Very Low

Summary:

Coadministration with buccal midazolam has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir has no clinically relevant effect on the pharmacokinetics of orally administered midazolam. Coadministration of oral midazolam (3 mg) and dolutegravir (25 mg once daily) to 10 subjects decreased midazolam AUC by 5%. No significant interaction is expected with buccal administration of midazolam as pharmacokinetic interactions are more pronounced for oral as compared to buccal or parenteral midazolam as CYP3A4 enzymes are also present in the upper gastro-intestinal tract. No interaction is expected with lamivudine.

Description:

In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration of midazolam (3 mg) and dolutegravir (25 mg once daily) decreased midazolam AUC by 5%.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of dolutegravir (25 mg once daily) and midazolam (3 mg single oral dose) was studied in 10 healthy subjects. Plasma midazolam AUC values were similar for the coadministration of midazolam with 25 mg dolutegravir (15.4 ng.h/ml on day 10 [CV, 41%]) and administration of midazolam alone (16.3 ng.h/ml on day1 [CV, 23%]); the GLS mean ratio was 0.945 (90% CI, 0.815, 1.10). These data demonstrate that dolutegravir does not induce or inhibit the CYP3A isozyme in vivo.

Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Min S, Song I, Borland J, et al. Antimicrob Agents Chemother. 2010; 54(1):254-8.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sotrovimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A; lamivudine is eliminated renally. Sotrovimab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Sotrovimab is not renally excreted or metabolized by CYP enzymes. Interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nirmatrelvir/ritonavir

Quality of Evidence: Very Low

Summary:

Coadministration with nirmatrelvir/ritonavir has not been studied. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A. Based on studies with ritonavir-boosted HIV protease inhibitors, ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of ritonavir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Whey Protein

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Whey protein is rapidly digested and absorbed as essential amino acids for use in physiological processes. Excess whey protein can be excreted in the urine by the kidneys. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Whey protein is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Enobosarm (Ostarine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enobosarm is primarily excreted in faeces as unchanged drug, with CYP3A4, UGT1A1 and UGT2B7 having a minor role in enobosarm metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP or UGT enzymes. Enobosarm is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ecdysterone (20-hydroxyecdysone, 20E)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ecdysterone has poor bioavailability and is predominantly metabolised once it reaches the gut microbiota. Unchanged ecdysterone and ecdysterone metabolites are excreted in both urine and faeces. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Ecdysterone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Telavancin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telavancin is primarily excreted as unchanged drug in the urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect telavancin elimination. Telavancin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rolapitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rolapitant is metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP3A4. Rolapitant is unlikely to have a clinically relevant effect dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Creatine monohydrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Creatine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Caffeine (anhydrous powder)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not affect CYP1A2. Caffeine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Beta-alanine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Beta-alanine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Branched chain amino acids (BCAAs; leucine, isoleucine, valine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. BCAAs are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atezolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lisdexamfetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisdexamfetamine is a prodrug of dexamfetamine and is not metabolized by CYP enzymes. Dexamfetamine is metabolized by CYP2D6 to some extent, whereas a large part is excreted unchanged. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Lisdexamfetamine has no clinically meaningful effect on drugs metabolized by CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nilutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nilutamide is metabolised by CYP2C19. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Netupitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Netupitant is metabolized primarily by CYP3A4 and to a lesser extent by CYP2C9 and CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Netupitant is unlikely to affect UGT1A1 but is a moderate inhibitor of CYP3A4. A clinically significant effect is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is mainly metabolised by CYP2D6, with minor contributions from CYP3A4 and CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Palonosetron and dolutegravir do not inhibit or induce CYPs at clinically relevant concentrations. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Remdesivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A whereas lamivudine is eliminated renally. Due to remdesivir’s rapid clearance, although remdesivir inhibits CYP3A4 it is unlikely to have a significant effect on dolutegravir. Remdesivir is a substrate of CYP2C8, CYP2D6, CYP3A4, OATP1B1 and P-gp, however, dolutegravir has no significant inhibitory or inducing effects on these enzymes and transporters. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pemigatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pemigatinib is mainly metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Pemigatinib does not inhibit or induce CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ferrous sulfate

Quality of Evidence: Very Low

Summary:

Coadministration with ferrous sulfate has not been studied. No interaction is expected with lamivudine. Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. A similar effect may occur with ferrous sulfate. When taken with food, Dovato and ferrous sulfate can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking ferrous sulfate.

Description:

Coadministration of iron supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 54%, 57% and 56%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing iron can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and56%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. When taken with food, Dovato and supplements containing iron can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=11) decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and 56%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir (n=10) decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. Dolutegravir and iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after iron supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pancreatic enzymes (pancrelipase, pancreatin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with pancreatic enzyme preparations containing amylase, lipase and protease.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lymecycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lymecycline is not metabolised and is excreted unchanged by renal and biliary routes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methocarbamol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Methocarbamol is metabolized in the liver by dealkylation, hydroxylation, and glucuronidation. Methocarbamol is unlikely to be a substrate or inhibitor of CYP enzymes. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ubrogepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ubrogepant is metabolized mainly by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ubrogepant is not expected to have a clinically significant effect on CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rimegepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimegepant is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9 and is a substrate of P-gp and BCRP. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Rimegepant is a weak inhibitor of CYP3A4 and is not expected to have a clinically relevant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ascorbic Acid (Vitamin C) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Dolutegravir does not interfere with this metabolic pathway. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. Lamivudine is predominantly eliminated unchanged via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Infigratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Infigratinib is mainly metabolized by CYP3A4 and to a lesser extent by FMO3. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Infigratinib does not inhibit or induce CYP3A4 and is unlikely to affect drugs metabolized by UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ibrutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibrutinib is metabolised primarily by CYP3A4 and to a minor extent by CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ibrutinib does not inhibit or induce CYP3A4 and is unlikely to affect drugs metabolized by UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Gilteritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gilteritinib is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Gilteritinib does not inhibit or induce CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fostamatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostamatinib is metabolised in the gut by alkaline phosphatase to the major active metabolite, R406, which is then metabolised by CYP3A4 and UGT1A9. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. R406 is considered as a weak inhibitor of UGT1A1 and CYP3A4 and is unlikely to have a clinically significant effect on dolutegravir exposure. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etanercept

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etanercept is a TNF-alpha inhibitor and is eliminated via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with etanercept may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Etanercept will normalize cytochrome activity (via reduction of cytokines) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing etanercept. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hyoscine hydrobromide (Scopolamine hydrobromide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine, derived from hyoscine hydrobromide, is metabolized by multiple pathways including CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Hyoscine is unlikely to significantly affect CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hyoscine (Scopolamine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine is metabolized by multiple pathways including CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Hyoscine is unlikely to significantly affect CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Darolutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Moxonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxonidine is only minimally metabolized and is eliminated renally by glomerular filtration and active secretion, mainly as unchanged moxonidine. The renal transporter involved in moxonidine excretion is unknown but does not seem to involve P-glycoprotein or renal organic cation (OCT) transporters. No interaction is expected with dolutegravir or with lamivudine (eliminated by OCT2).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tolvaptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolvaptan is extensively metabolized in the liver almost exclusively by CYP3A. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Tolvaptan is not expected to have clinically significant effect on drugs metabolized by CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methotrexate (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion (OAT1, OAT3 mediate methotrexate transport in the kidney whereas MRP4 and BCRP mediate methotrexate efflux in the urine). No interaction is expected with dolutegravir. There is no risk for competition for active renal transport mechanisms as lamivudine is eliminated by other renal transporters. Results of a clinical study evaluating the co-administration of high-dose of intravenous methotrexate for chemotherapy with NRTIs (abacavir/lamivudine or emtricitabine/tenofovir-DF) or integrase inhibitors showed that methotrexate half-life was not prolonged. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Description:

Methotrexate concentrations were determined in 43 HIV+ patients treated with ARVs and chemotherapy containing high dose methotrexate (3g/m2). Methotrexate elimination half-life was not affected by use of NNRTIs, integrase inhibitors or NRTIs (tenofovir /emtricitabine or abacavir/lamivudine).

The pharmacokinetics of high dose methotrexate in people living with HIV on antiretroviral therapy. Dalla Pria A, Bendle M, Ramaswami R, et al. Cancer Chemother Pharmacol, 2016, 77:653-657.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nizatidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nizatidine is primarily eliminated via tubular secretion and glomerular filtration in urine. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Nizatidine is unlikely to alter absorption of lamivudine.

Description:

Coadministration has not been studied but a clinically significant interaction is unlikely. No dosage adjustment is necessary.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rezafungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rezafungin is primarily eliminated unchanged by faecal excretion. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect rezafungin elimination. Rezafungin is unlikely to inhibit or induce UGT1A1 or CYP3A4 at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ispaghula husk

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ispaghula husk passes predominantly unchanged through the gastrointestinal tract and there is little opportunity for marked absorption into or metabolism by the body. The mode of action of ispaghula husk is physical and does not depend on absorption into the systemic circulation. However, ispaghula husk may delay or reduce gastrointestinal absorption of other drugs and it is advisable to separate administration of ispaghula husk and orally administered drugs by 1 hour. [Note: this interaction is not specific for dolutegravir and lamivudine, but for any oral medication taken with ispaghula husk.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Repotrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repotrectinib is primarily metabolized by CYP3A4 followed by secondary glucuronidation. Repotrectinib is also a P-gp substrate. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP3A4 or UGTs. Repotrectinib is unlikely to affect UGT1A1. Repotrectinib is a moderate CYP3A4 inducer but a clinically significant effect on dolutegravir exposure is unlikely as CYP3A4 represents a minor dolutegravir metabolic pathway. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Moexipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moexipril is rapidly converted to the active metabolite moexiprilat, likely via carboxylesterases . Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect moexipril metabolism. Moexipril is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Elagolix

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elagolix is primarily metabolized by CYP3A4 and is a substrate of P-gp and OATP1B1. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP3A4. Elagolix is unlikely to affect UGT1A1. Elagolix is a weak to moderate CYP3A4 inducer but a clinically significant effect on dolutegravir exposure is unlikely as CYP3A4 represents a minor dolutegravir metabolic pathway, no dose adjustment is necessary. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Avatrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Avatrombopag does not inhibit or induce CYP3A. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Etoricoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoricoxib is metabolised by CYPs 3A4 (main), 2D6, 2C9, 1A2 and 2C19. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Etoricoxib is not expected to affect CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Terbutaline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbutaline is eliminated primarily as sulfate and glucuronide conjugates with oral dosing and excreted mainly unchanged with inhalation dosing.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Thiotepa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thiotepa is rapidly metabolised by CYP3A4 and CYP2B6 to the active alkylating metabolite TEPA. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYPs. Thiotepa is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Copanlisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYPs. Copanlisib does not inhibit or induce UGT1A1 or CYP3A4. Copanlisib is an inhibitor of MATE2-k and may increase lamivudine concentrations but a clinically relevant interaction is not expected given the multiple transporters involved in the elimination of lamivudine and the good tolerability of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dexlansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. However, data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine.

Description:

Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment as solubility of dolutegravir is not influenced by changes in gastric pH and coadministration with omeprazole had minimal effect on dolutegravir exposure. Coadministration of omeprazole (40 mg once daily) and single doses of dolutegravir (50 mg single dose, administered 2 hours after omeprazole) was studied in 12 HIV-negative subjects and had no significant effect on dolutegravir exposure (no change in AUC, 8% decrease in Cmax, 5% decrease in Cmin).

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Zinc

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body and is excreted in the faeces with traces appearing in the urine. Coadministration may decrease dolutegravir concentrations due to chelation with the polyvalent zinc cations. Dolutegravir/lamivudine should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations (such as zinc) or taken together with food.

Description:

Coadministration may decrease dolutegravir concentrations. Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Drotaverine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drotaverine is metabolised in the liver by O-deethylation. Clinically relevant pharmacokinetic interactions have not been reported. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Bismuth subsalicylate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Bismuth subsalicylate is unlikely to affect UGT1A1 or CYP3A4. Significant interactions are not expected with lamivudine. However, dolutegravir may be subject to chelation by high concentrations of trivalent bismuth cations which may result in reduced dolutegravir concentrations. Dovato should be taken 2 hours before or 6 hours after bismuth subsalicylate.

Description:

Coadministration may decrease dolutegravir concentrations. Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dimethyl fumarate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Benzatropine (Benztropine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Colesevelam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after dolutegravir/lamivudine to minimize the risk of reduced absorption.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cytisine (Cytisinicline)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Coenzyme Q10 (Ubidecarenone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Romidepsin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Romidepsin is mainly metabolised by CYP3A4 with a minor contribution from CYPs 3A5, 1A1, 2B6 and 2C19, and is a substrate of P-gp. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYPs. Romidepsin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ropivacaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ropivacaine is mainly metabolised by CYP1A2, with CYP3A4 having a minor role. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP1A2. Ropivacaine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Busulfan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect busulfan metabolism. Busulfan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Dolutegravir/ Lamivudine/ Tenofovir-DF (DTG/3TC/TDF; TLD)

Quality of Evidence: Very Low

Summary:

Dolutegravir/lamivudine/tenofovir-DF and Dovato (dolutegravir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both regimens contain dolutegravir and lamivudine and should not be taken with any other medicinal products also containing dolutegravir and lamivudine.

Description:

Dolutegravir, lamivudine and tenofovir disoproxil fumarate tablets should not be taken with any other medicinal products containing lamivudine.

Dolutegravir, Lamivudine, and Tenofovir Disoproxil Fumarate Tablets WHOPAR part 4, Strides Pharma Ltd, August 2024.

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions. Coadministration of dolutegravir and tenofovir increased dolutegravir AUC by 1% and decreased Cmax and Cmin by 3% and 8%. There was no change in tenofovir pharmacokinetics. No dose adjustment is necessary when Dovato is combined with tenofovir.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended. No clinically significant differences in the pharmacokinetics of tenofovir (organic anion transporter [OAT]1 and OAT3 substrates) were observed when coadministered with dolutegravir.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desmopressin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cyanocobalamin (Vitamin B12) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pyridoxine (Vitamin B6) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyridoxine is absorbed from the GI tract and is converted to the active form pyridoxal phosphate. It is excreted in the urine as 4-pyridoxic acid.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lomitapide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lomitapide is predominantly metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Lomitapide is a weak inhibitor of CYP3A4 but no effect on dolutegravir exposure is expected. Dolutegravir is unlikely to affect CYP3A4. Significant interactions are not expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Erdafitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erdafitinib is primarily metabolised by CYP2C9 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Erdafitinib is a time dependent inhibitor and inducer of CYP3A4 (net effect seems to be inhibition based on pharmacokinetic simulation) but is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Belimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with belimumab may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Belimumab was shown to lower IFN and IL-6/10 and is expected to normalize metabolism but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing belimumab. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bendamustine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Bendamustine does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cinacalcet

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally. Cinacalcet does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fezolinetant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fezolinetant is primarily metabolised by CYP1A2 and to a lesser extent by CYP2C9 and CYP2C19. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYP enzymes. Fezolinetant is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Methylergometrine (Methylergonovine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylergometrine is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Methylergometrine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Naratriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naratriptan is metabolised by a wide range of CYP enzymes and is mainly excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Significant metabolic drug interactions with naratriptan are not anticipated.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Galcanezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Galcanezumab is a monoclonal IgG4 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Galcanezumab is not metabolized by CYP enzymes; interactions with substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Erenumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erenumab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Erenumab is not metabolized by CYP enzymes; interactions with substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eptinezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eptinezumab is a monoclonal IgG1 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Eptinezumab is not metabolized by CYP enzymes; interactions with substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Homeopathic remedies

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence that homeopathic remedies interact with conventional medicines, provided they are from a reputable source, and of the strength stated. However, caution may be required as some remedies termed “low potency” are less dilute, and some remedies may contain alcohol.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vedolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vedolizumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Interactions with drug metabolizing enzymes or drug transporters are unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tinzaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is partially metabolised by desulfation and depolymerization, and then renally excreted. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Raloxifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raloxifene undergoes hepatic glucuronidation (by UGT1A1 and UGT1A9) and extra-hepatic glucuronidation (by UGT1A8 and UGT1A10). Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Raloxifene is not expected to affect drugs metabolised by CYP enzymes. Dolutegravir is unlikely to affect drugs metabolized by UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bumetanide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. In vitro data suggest that bumetanide inhibits OAT1 but no interaction is expected with lamivudine as it is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flupentixol (Flupenthixol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flupentixol is metabolised by sulfoxidation and dealkylation and is a substrate of UGT. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Flupentixol is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tofacitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tofacitinib undergoes hepatic metabolism (70%) primarily by CYP3A4 with a minor contribution from CYP2C19, and is eliminated renally (30%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Tofacitinib does not affect UGT1A1 or CYP3A4. Dolutegravir is unlikely to affect tofacitinib metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Procyclidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Little is known about procyclidine metabolism but it is likely to be metabolized by CYP450s and glucuronidated. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect procyclidine metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Psyllium husk

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Psyllium husk passes predominantly unchanged through the gastrointestinal tract and there is little opportunity for marked absorption into or metabolism by the body. The mode of action of psyllium husk is physical and does not depend on absorption into the systemic circulation. However, psyllium husk may delay or reduce gastrointestinal absorption of other drugs and it is advisable to separate administration of psyllium husk and orally administered drugs if possible. [Note: this interaction is not specific for dolutegravir and lamivudine, but for any oral medication taken with psyllium husk.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Orphenadrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Orphenadrine is extensively metabolized (limited information on metabolic pathway). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect orphenadrine metabolism. Orphenadrine inhibits CYP3A4 in vitro, but is unlikely to have a clinically relevant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cyclizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Minoxidil (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minoxidil is a substrate of UGTs (the specific UGTs have not been well described). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. The likelihood of clinically significant interactions is low as only 1-2% of a topically applied minoxidil dose is absorbed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Minoxidil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minoxidil is a substrate of UGTs (the specific UGTs have not been well described). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Minoxidil is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Deferasirox

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Deferasirox and dolutegravir are unlikely to affect UGTs. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease dolutegravir concentrations. Significant interactions are not expected lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ospemifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ospemifene is primarily metabolised by CYP3A4 and CYP2C9; CYP2C19 and UGTs 1A3, 2B7, 1A1 and 1A8 also contribute to its metabolism. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP or UGT enzymes. Ospemifene is unlikely to have a clinically significant effect on CYP3A4 or UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Macrogol (Polyethylene glycol, PEG 3350, PEG 4000)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Macrogol is unabsorbed from the gastrointestinal tract and is excreted, unaltered, in faeces. Any macrogol that does enter the circulation is excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. However, the absorption of other oral medications may be reduced due to increased gastrointestinal transit with macrogol. Do not take macrogol within two hours of taking another oral medication. [Note: this interaction is not specific for dolutegravir and lamivudine but for any oral medication taken with macrogol.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dupilumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dupilumab is an IgG4 monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No metabolic drug interactions are expected with dupilumab.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ruxolitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ruxolitinib is metabolized by CYP3A4 (major) and CYP2C9 (minor), and does not inhibit or induce CYPs. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nitazoxanide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide, which is subsequently glucuronidated. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No significant interaction is expected when nitazoxanide is administered with drugs that are metabolized by, or that inhibit or induce CYP enzymes. No interaction Is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Canakinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Baricitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP or UGT enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Melatonin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Melatonin is metabolized mainly by CYP1A2, with CYP1A1 and CYP2C19 involved to a minor extent. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally. Melatonin induced CYP3A in vitro at supra-therapeutic concentrations, but no effect on dolutegravir is expected at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Anakinra

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Pralsetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pralsetinib is metabolized by CYP3A4 and UGT1A4 and to a lesser extent by CYP2D6 and CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. In vitro data indicate that pralsetinib has inhibitory and inducing effects on CYP3A4. Pralsetinib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. Lamivudine is eliminated renally. Pralsetinib is an inhibitor of MATE1 and MATE2-k and may increase concentrations of lamivudine but a clinically relevant interaction is not expected given the good tolerability of lamivudine and no a priori dose adjustment of lamivudine is needed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pexidartinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pexidartinib is metabolized by CYP3A4 and UGT1A4 and is a moderate inducer of CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Pexidartinib is a moderate inducer of CYP3A4 but is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valganciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valganciclovir is rapidly hydrolysed to ganciclovir. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Valganciclovir and ganciclovir are unlikely to affect UGT1A1 or CYP3A4. Dolutegravir is unlikely to affect ganciclovir elimination. A clinically relevant interaction is unlikely with lamivudine as it is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isosorbide mononitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isosorbide mononitrate is completely absorbed and is not subject to first pass metabolism by the liver. It is denitrated and glucuronidated to inactive metabolites before being excreted mainly in the urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Only ~25% of an isosorbide mononitrate dose is glucuronidated, there is therefore little potential for clinically significant interactions with dolutegravir via competition for glucuronidation pathways. As renal elimination of unchanged isosorbide mononitrate is a minor pathway, there is also little potential for interaction with lamivudine via competition for renal elimination pathways

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Indometacin (Indomethacin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indometacin is metabolized predominantly by acylation followed by glucuronidation (mainly UGT2B7 and partly by UGT1A9). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Indometacin is unlikely to affect UGT1A1 or CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lenvatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenvatinib is extensively metabolised by multiple enzymes, mainly CYP3A4 and aldehyde oxidase. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lenvatinib is not expected to have a clinically significant effect on CYP3A4 or UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Risedronic acid (Risedronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risedronate is not metabolized and is excreted unchanged primarily by the kidney. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Risedronate does not induce or inhibit hepatic drug metabolizing enzymes such as UGTs and CYPs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Olaratumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olaratumab is a monoclonal IgG1 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No interactions are expected with olaratumab and substrates, inhibitors or inducers of CYP enzymes or other metabolising enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ofatumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofatumumab is a fully human monoclonal IgG1 antibody; elimination occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No interactions are expected with ofatumumab and substrates, inhibitors or inducers of CYP enzymes, other metabolising enzymes or transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Obinutuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Obinutuzumab is a monoclonal IgG antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No interactions are expected with obinutuzumab and substrates, inhibitors or inducers of CYPs, UGTs or P-gp.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Inotuzumab ozogamicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inotuzumab ozogamicin is a humanized monoclonal antibody; elimination occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No interactions are expected with inotuzumab ozogamicin and substrates, inhibitors or inducers of CYP enzymes, UGT enzymes or transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Elotuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elotuzumab is a monoclonal IgG antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No interactions are expected with elotuzumab and substrates, inhibitors or inducers of CYP or other drug metabolizing enzymes.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Tegafur/ Gimeracil/ Oteracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Tegafur is metabolised to the active compound 5-fluorouracil by CYP2A6; gimeracil and oteracil are not metabolised by CYPs. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Tegafur, gimeracil, oteracil and 5-fluorouracil do not inhibit or induce CYP3A4. Lamivudine is eliminated renally. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. Nucleoside analogues such as abacavir and lamivudine may compete for this metabolic pathway. The clinical relevance of this interaction is unknown.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trifluridine/Tipiracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trifluridine is mainly metabolised by thymidine phosphorylase (TPase) to form the inactive metabolite 5-(trifluoromethyl) uracil (FTY); tipiracil is not metabolised. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Trifluridine, tipiracil and FTY do not inhibit or induce CYPs. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Niraparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Niraparib is metabolized by carboxylesterases and UGTs. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. Niraparib is unlikely to affect CYP3A4 and is unlikely to have a clinically relevant effect on UGTs. Lamivudine is eliminated renally by OCT2, MATE1 and MATE2-k transporters. Niraparib is an inhibitor of MATE1 and MATE2-K. Coadministration may increase lamivudine concentrations but a clinically relevant interaction is not expected given the good tolerability of lamivudine and no a priori dose adjustment of lamivudine is needed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ixazomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ixazomib is extensively metabolised by multiple CYP and non-CYP enzymes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Ixazomib does not induce or inhibit CYPs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eribulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eribulin is primarily eliminated via biliary excretion and is minimally metabolized (metabolism by CYP3A4 is negligible). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Eribulin is a weak inhibitor of CYP3A4 and is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Talazoparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Talazoparib undergoes minimal hepatic metabolism and is primarily excreted renally via P-gp and BCRP. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce P-gp. Talazoparib is not expected to affect drugs metabolised CYP or UGT enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Asciminib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs or UGTs at clinically relevant concentrations. Asciminib is a weak inhibitor of CYP3A4 but is unlikely to cause a clinically significant increase in dolutegravir exposure. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sotorasib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotorasib is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Sotorasib is a moderate inducer of CYP3A4 and is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lurasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYPs at clinically relevant concentrations. Lurasidone does not significantly inhibit or induce CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Selpercatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selpercatinib is metabolized predominantly by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Selpercatinib is a weak inhibitor of CYP3A4 but is unlikely to have a significant effect on dolutegravir. Selpercatinib is an inhibitor of MATE1 and may increase lamivudine concentrations but a clinically relevant interaction is not expected given the multiple transporters involved in the elimination of lamivudine and the good tolerability of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mebeverine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mebeverine is mainly metabolized by esterases. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Sucralfate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sucralfate is only minimally absorbed from the gastrointestinal tract. Sucralfate contains aluminium and may decrease dolutegravir concentrations due to chelation with polyvalent cations. Dolutegravir/lamivudine should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations, such as sucralfate.

Description:

Sucralfate is expected to decrease dolutegravir concentrations. Administer Dovato 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, January 2023.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Risankizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risankizumab is primarily metabolised through catabolic pathways similarly to endogenous IgG. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Risankizumab is unlikely to have a clinically relevant effect on CYP3A.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ribociclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ribociclib is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ribociclib does not affect UGT enzymes but is a strong CYP3A4 inhibitor at the 600 mg dose and a moderate CYP3A4 inhibitor at the 400 mg dose. A clinically significant effect is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Crizotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Crizotinib is mainly metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Crizotinib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Dabrafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Dabrafenib is a strong inducer of CYP3A4 and may induce UGTs and therefore has the potential to decrease dolutegravir exposure. Based on the drug-drug interaction study with rifampicin (a strong inducer), a dose adjustment of dolutegravir to 50 mg twice daily is recommended when coadministered with dabrafenib in the absence of integrase class resistance. This dose adjustment should be maintained for approximately 2 weeks after stopping dabrafenib as the inducing effect may persist after discontinuation of a strong inducer. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Dacomitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Dacomitinib does not inhibit or induce CYP3A4, but inhibits UGT1A1 and could increase dolutegravir exposure, although to a modest extent. No dose adjustment is needed. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Duvelisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duvelisib is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Duvelisib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Vemurafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vemurafenib is metabolized by CYP3A4 and is a moderate inducer of CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Vemurafenib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Infliximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Infliximab is a TNF-alpha inhibitor and is eliminated via binding to its target antigen. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with infliximab may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Infliximab will normalize cytochrome activity (via reduction of cytokines) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing infliximab. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ustekinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ustekinumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ceritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceritinib is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ceritinib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Entrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entrectinib is mainly metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Entrectinib does not significantly inhibit CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Encorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Encorafenib is mainly metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Encorafenib was shown to inhibit and induce CYP3A4 in vitro, however, simulations suggest that a minor to moderate interaction is expected with CYP3A4 substrates. No a priori dosage adjustment is needed for dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fedratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fedratinib is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C19 and FMO3. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Fedratinib is a strong inhibitor of CYP3A4 but is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No dose adjustment is needed. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Azilsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azilsartan is metabolized mainly by CYP2C9. Dolutegravir does not inhibit or induce CYP2C9. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Cabotegravir/rilpivirine [long acting] (CAB/RPV LA)

Quality of Evidence: Very Low

Summary:

Cabenuva (cabotegravir LA, rilpivirine LA) and Dovato (dolutegravir/lamivudine) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Description:

Vocabria and rilpivirine injections are intended for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral medicinal products for the treatment of HIV. Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other antiretroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors or ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Rekambys should not be administered with other antiretroviral medicinal products, except for cabotegravir injection for the treatment of HIV-1 infection. From a drug interaction perspective, there are no limitations on the use of other antiretroviral medicinal products after discontinuing Rekambys.

Rekambys (rilpivirine prolonged release injection) European Summary of Product Characteristics, Janssen-Cilag, January 2021.

Because Cabenuva is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of Cabenuva.

Cabenuva (cabotegravir/rilpivirine extended release injection) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Venetoclax

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venetoclax is metabolised by CYP3A4. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A whereas lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fremanezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fremanuzemab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Fremanuzemab is not metabolized by CYP enzymes; interactions with substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clotrimazole (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant interaction is unlikely with the topical use of clotrimazole as it is minimally absorbed

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pomalidomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pomalidomide is metabolised by CYP1A2 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Pomalidomide does not inhibit or induce CYPs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pemetrexed

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pemetrexed is not appreciably metabolised and is primarily eliminated unchanged renally (70-90% recovered in 24 hours). Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Pemetrexed is not expected to affect drugs metabolised by CYP3A4. Pemetrexed is a substrate of OAT3, but lamivudine is eliminated by other renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Meloxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meloxicam is metabolised mainly by CYP2C9, with a minor contribution from CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ketoprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketoprofen is mainly metabolized by multiple UGTs. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGT enzymes at clinically relevant concentrations. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Panobinostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Panobinostat is metabolized by non-CYP and CYP mediated routes; approximately 40% of panobinostat is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Panobinostat is unlikely to have significant effect on drugs metabolised by CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Palbociclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palbociclib is metabolised by CYP3A and SULT2A1. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Palbociclib is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bicalutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Bicalutamide is a weak inhibitor of CYP3A4 and inhibited UGT1A9 in vitro but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Enfuvirtide (ENF, T20)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with enfuvirtide would be possible from a pharmacokinetic standpoint. Enfuvirtide undergoes catabolism to its constituent amino acids. This metabolic pathway is unlikely to be affected by coadministered drugs. The potential for metabolic interactions with enfuvirtide is low.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cemiplimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Sotalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sotalol is mainly eliminated unchanged by the kidney by glomerular filtration and to a small degree by active secretion via the renal transporters OCT2 and MATE1. Dolutegravir may increase sotalol exposure via inhibition of OCT2. Based on the drug-drug interaction study with dolutegravir and metformin (another drug transported by OCT2 and MATE1), the increase in sotalol exposure is expected to be ~80% or ~110% when dolutegravir is administered once daily and twice daily, respectively. In addition, there is potential for competition with sotalol and lamivudine for elimination via renal transport proteins, which may lead to increased concentrations of either drug. It is recommended to start sotalol at a lower dose and adjust dosage until the desired clinical effect is achieved.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Emtricitabine/Tenofovir alafenamide for PrEP (FTC/TAF, PrEP)

Quality of Evidence: Very Low

Summary:

Emtricitabine and tenofovir alafenamide used as PrEP are not expected to be coadministered with antiretrovirals. Dovato (dolutegravir/lamivudine) and emtricitabine/tenofovir alafenamide should not be coadministered. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Description:

Descovy should not be administered concomitantly with medicinal products containing lamivudine.

Descovy Summary of Product Characteristics, Gilead Sciences Ltd, April 2022.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Midodrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midodrine is a prodrug converted to its active metabolite desglymidodrine in various tissues. Desglymidodrine is mainly metabolized by CYP2D6 and to a lesser extent by CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and has no inhibitory or inducing effects. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pretomanid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pretomanid is metabolized in the liver via multiple reductive and oxidative pathways with CYP3A4 mediated metabolism representing 20% of its metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Terlipressin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terlipressin is metabolized by various peptidases in the liver and kidney.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Octreotide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Octreotide has been reported to be heavily metabolized in the liver but the metabolic pathway is unclear. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. No interactions are expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ketorolac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketorolac is partly eliminated renally and via hepatic metabolism by CYP2C8, CYP2C9 and UGT2B7. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Ketorolac does not inhibit or induce UGTs or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sodium valproate

Quality of Evidence: Very Low

Summary:

Coadministration with sodium valproate has not been studied but studies with valproic acid suggest a clinically significant interaction is unlikely. Sodium valproate circulates in plasma as the valproate ion. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Valproic acid has been shown to significantly reduce total dolutegravir concentrations due to protein binding displacement. However, this interaction is not clinically relevant since the concentrations of free dolutegravir (pharmacologically active) are not decreased. No interaction is expected with lamivudine.

Description:

Total and unbound dolutegravir plasma concentrations were measured in HIV-infected individuals on once-daily 50 mg dolutegravir-containing combination ART prior to and after the concomitant administration of valproic acid (30 mg/kg/day orally divided into two equal doses). Data from 6 participants receiving valproic acid showed that during valproic acid administration, total dolutegravir levels decreased sharply from 1.36 mg/L on day 0 to 0.85 mg/L, 0.31 and 0.14 mg/L on days 1, 7 and 14. Total dolutegravir concentrations in the 4 control participants not receiving valproic acid remained comparable during the same period: 1.27 ± 1.49 mg/L. A parallel increase was observed in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. This study supports that the decrease in total dolutegravir concentrations in presence of valproic acid is mainly due to protein binding displacement of dolutegravir by valproic acid. If dolutegravir is taken with food, this interaction is probably not clinically relevant.

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement. Bollen PDJ, Prins HAB, Colbers A, et al. J Antimicrob Chemother. 2021; 76(5):1273-1276.

A retrospective analysis of dolutegravir trough concentrations in 363 samples (from 149 patients) showed lower trough concentrations in 11 samples from 7 patients on valproic acid (0.068 µg/ml vs 0.557 µg/ml). Detailed pharmacokinetic sampling was performed in two hospitalized patients requiring valproic acid while on dolutegravir-based regimens. When compared to a mean reference AUC value of 75.1 µg.h/mL for dolutegravir twice daily, dolutegravir AUC in the first patient was 82% lower with IV valproic acid and 87-91% lower with oral valproic acid. In the second patient, dolutegravir AUC was 80% lower with oral valproic acid when compared to the mean reference AUC.

Lower dolutegravir plasma concentrations in HIV-positive patients receiving valproic acid. Palazzo A, Trunfio M, Pirriatore V, et al. J Antimicrob Chemother, 2018, 73(3): 826-827.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dexamethasone (doses above 16 mg)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Dexamethasone could potentially decrease dolutegravir concentrations, but this is unlikely to be of clinical significance as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tesamorelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tesamorelin is a peptide analogue which is likely eliminated by catabolism to its constituent amino acids.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valproic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valproic acid circulates in plasma as the valproate ion. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Valproic acid has been shown to significantly reduce total dolutegravir concentrations due to protein binding displacement. However, this interaction is not clinically relevant since the concentrations of free dolutegravir (pharmacologically active) are not decreased. No interaction is expected with lamivudine.

Description:

Total and unbound dolutegravir plasma concentrations were measured in HIV-infected individuals on once-daily 50 mg dolutegravir-containing combination ART prior to and after the concomitant administration of valproic acid (30 mg/kg/day orally divided into two equal doses). Data from 6 participants receiving valproic acid showed that during valproic acid administration, total dolutegravir levels decreased sharply from 1.36 mg/L on day 0 to 0.85 mg/L, 0.31 and 0.14 mg/L on days 1, 7 and 14. Total dolutegravir concentrations in the 4 control participants not receiving valproic acid remained comparable during the same period: 1.27 ± 1.49 mg/L. A parallel increase was observed in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. This study supports that the decrease in total dolutegravir concentrations in presence of valproic acid is mainly due to protein binding displacement of dolutegravir by valproic acid. If dolutegravir is taken with food, this interaction is probably not clinically relevant.

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement. Bollen PDJ, Prins HAB, Colbers A, et al. J Antimicrob Chemother. 2021; 76(5):1273-1276.

A retrospective analysis of dolutegravir trough concentrations in 363 samples (from 149 patients) showed lower trough concentrations in 11 samples from 7 patients on valproic acid (0.068 µg/ml vs 0.557 µg/ml). Detailed pharmacokinetic sampling was performed in two hospitalized patients requiring valproic acid while on dolutegravir-based regimens. When compared to a mean reference AUC value of 75.1 µg.h/mL for dolutegravir twice daily, dolutegravir AUC in the first patient was 82% lower with IV valproic acid and 87-91% lower with oral valproic acid. In the second patient, dolutegravir AUC was 80% lower with oral valproic acid when compared to the mean reference AUC.

Lower dolutegravir plasma concentrations in HIV-positive patients receiving valproic acid. Palazzo A, Trunfio M, Pirriatore V, et al. J Antimicrob Chemother, 2018, 73(3): 826-827.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nicotine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotine is metabolised mainly by CYP2A6 which is not affected by dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Yohimbine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Yohimbine is predominantly metabolized by CYP2D6 with some participation of CYP3A4 whereas dolutegravir is mainly metabolized by UGT1A1. Dolutegravir has no inhibitory effects on CYP enzymes. Lamivudine does not interfere with yohimbine metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Neratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Neratinib is metabolised mainly by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Neratinib does not inhibit or induce CYPs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nivolumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nivolumab is a monoclonal IgG4 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Valproate semisodium (Divalproex sodium)

Quality of Evidence: Very Low

Summary:

Coadministration with valproate semisodium (divalproex semisodium) has not been studied but studies with valproic acid suggest a clinically significant interaction is unlikely. Valproate semisodium (divalproex semisodium) is a stable coordination compound comprised of sodium valproate and valproic acid and dissociates to the valproate ion in the gastrointestinal tract. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Although valproic acid significantly reduced total dolutegravir concentrations due to protein binding displacement, this interaction is not clinically relevant since the concentrations of pharmacologically active free (unbound) dolutegravir are not decreased. No interaction is expected with lamivudine.

Description:

Total and unbound dolutegravir plasma concentrations were measured in HIV-infected individuals on once-daily 50 mg dolutegravir-containing combination ART prior to and after the concomitant administration of valproic acid (30 mg/kg/day orally divided into two equal doses). Data from 6 participants receiving valproic acid showed that during valproic acid administration, total dolutegravir levels decreased sharply from 1.36 mg/L on day 0 to 0.85 mg/L, 0.31 and 0.14 mg/L on days 1, 7 and 14. Total dolutegravir concentrations in the 4 control participants not receiving valproic acid remained comparable during the same period: 1.27 ± 1.49 mg/L. A parallel increase was observed in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. This study supports that the decrease in total dolutegravir concentrations in presence of valproic acid is mainly due to protein binding displacement of dolutegravir by valproic acid. If dolutegravir is taken with food, this interaction is probably not clinically relevant.

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement. Bollen PDJ, Prins HAB, Colbers A, et al. J Antimicrob Chemother. 2021; 76(5):1273-1276.

A retrospective analysis of dolutegravir trough concentrations in 363 samples (from 149 patients) showed lower trough concentrations in 11 samples from 7 patients on valproic acid (0.068 µg/ml vs 0.557 µg/ml). Detailed pharmacokinetic sampling was performed in two hospitalized patients requiring valproic acid while on dolutegravir-based regimens. When compared to a mean reference AUC value of 75.1 µg.h/mL for dolutegravir twice daily, dolutegravir AUC in the first patient was 82% lower with IV valproic acid and 87-91% lower with oral valproic acid. In the second patient, dolutegravir AUC was 80% lower with oral valproic acid when compared to the mean reference AUC.

Lower dolutegravir plasma concentrations in HIV-positive patients receiving valproic acid. Palazzo A, Trunfio M, Pirriatore V, et al. J Antimicrob Chemother, 2018, 73(3): 826-827.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Necitumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Necitumumab is an IgG1 monoclonal antibody and is eliminated via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Flutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flutamide is predominantly metabolised by CYP1A2 and to a lesser extent by CYP3A4. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Flutamide induced CYP3A4 in vitro but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Leflunomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leflunomide is primarily metabolized to the active metabolite teriflunomide (A771726). Metabolism is not controlled by a single enzyme and has been shown to occur in microsomal and cytosolic cellular fractions. Interaction studies with the non-specific CYP inhibitor cimetidine and with the strong inducer rifampicin suggest that CYP metabolism plays a minor role in leflunomide metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally. Teriflunomide had no significant effect on CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alemtuzumab (Cancer therapy)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desloratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Desloratadine does not inhibit CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nintedanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nintedanib is primarily metabolised by esterases to the active metabolite BIBF 1202, with CYP3A4 contributing to a minor extent. BIBF 1202 is subsequently glucuronidated by UGTs 1A1, 1A7, 1A8 and 1A10. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glucose monohydrate (IV)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glucose is rapidly absorbed into cells and metabolized into carbon dioxide and water with the release of energy. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mobocertinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mobocertinib is mainly metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Mobocertinib is a weak inducer of CYP3A4 and is unlikely to have a clinically relevant effect on dolutegravir given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Perampanel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perampanel is metabolised mainly by CYP3A4/5. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Perampanel is unlikely to have a clinically relevant effect on UGTs but may induce CYP3A4 at high doses (12 mg/day). However, a clinically significant effect on dolutegravir is unlikely as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Mitotane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Mitotane is primarily metabolized in adrenal cells and is a strong inducer of CYP3A4. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Coadministration is expected to decrease dolutegravir concentrations. Given the persisting inducing effect upon discontinuation of a strong inducer and the very long elimination half-life (18-159 days) of mitotane, a dose increase to overcome this interaction is unlikely to be feasible. Dolutegravir should not be used 3-6 months after the last dose of mitotane given the very long elimination half-life of mitotane. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Midostaurin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midostaurin is metabolised mainly by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Midostaurin is a weak-moderate inducer of CYP3A4 but is not expected to have a clinically relevant effect on dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Sevelamer

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sevelamer is a resin not absorbed from the GI tract that may affect the bioavailability of other medicinal products. In the absence of data, when administering any medicinal product where a reduction in the bioavailability could have a clinically significant effect on safety or efficacy, the medicinal product should be administered at least one hour before or three hours after sevelamer. [Note: this interaction is not specific for dolutegravir and lamivudine, but for any medication taken with sevelamer.]

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Fostemsavir (FTR)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. No interaction is expected with lamivudine.

Description:

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Fampridine (Dalfampridine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Fampridine is metabolized by CYP2E1 but is predominantly eliminated unchanged by the kidney with active secretion by OCT2. Dolutegravir inhibits OCT2 and has the potential to cause seizures due to increased fampridine plasma concentration via OCT2 inhibition. Coadministration is contraindicated in the European product label for dolutegravir/lamivudine, but the US product label advises that the potential benefits of taking dalfampridine should be considered against the risk of seizures.

Description:

Co-administration is contraindicated with medicinal products with narrow therapeutic windows, that are substrates of organic cation transporter (OCT) 2, including but not limited to fampridine (also known as dalfampridine). Co-administration of dolutegravir has the potential to cause seizures due to increased fampridine plasma concentration via inhibition of OCT2 transporter; co-administration has not been studied. Fampridine co-administration with Dovato is contraindicated.

Dovato Summary of Product Characteristics, ViiV Healthcare Ltd, May 2020.

Coadministration may increase plasma concentrations of dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with Dovato should be considered against the risk of seizures in these patients.

Dovato US Prescribing Information, ViiV Healthcare, March 2020.

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Colestyramine (cholestyramine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for dolutegravir and lamivudine, but for any medication taken with colestyramine.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hydroxychloroquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxychloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Due to the multiple elimination pathways, a clinically significant interaction with lamivudine is unlikely.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Enzalutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Enzalutamide is primarily metabolized by CYP2C8 and is a strong inducer of CYP3A4. Enzalutamide can induce UGT1A1. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Coadministration is expected to decrease dolutegravir concentrations, thus dolutegravir should be administered at 50 mg twice daily in the absence of integrase class resistance. In the presence of integrase class resistance this combination should be avoided. Enzalutamide has a long half-life (5.8 days), therefore the dolutegravir dose should be kept at 50 mg twice daily for a minimum of 2 weeks (but preferably 4 weeks) following cessation of enzalutamide due to the persisting inducing effect upon discontinuation of a strong inducer. Enzalutamide does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tocilizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on tocilizumab is expected as it is an IL-6 receptor monoclonal antibody and likely undergoes elimination via binding to its target antigen. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A whereas lamivudine is eliminated renally. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Tocilizumab, per se, has no inhibitory or inducing effects on cytochromes. Tocilizumab will normalize cytochrome activity (via inhibition of IL-6) but no a priori dose adjustment is required.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lomustine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lomustine is extensively metabolised by CYPs, with animal studies suggesting involvement of CYP2C19, CYP2D6 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Larotrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Larotrectinib is mainly metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Larotrectinib is a weak inhibitor of CYP3A4 and a weak inducer of UGTs in vitro but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ivosidenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ivosidenib is primarily metabolized by CYP3A4. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ivosidenib has the potential to induce UGTs and may decrease dolutegravir concentrations. Dolutegravir should be administered at 50 mg twice daily in the absence of integrase class resistance. In the presence of integrase class resistance this combination should be avoided. Ivosidenib has a long half-life (approximately 2.4 to 5.4 days depending on indication), therefore a minimum of 2 weeks, but preferably 4 weeks, cessation period is recommended prior to initiation of dolutegravir due to the persisting inducing effect upon discontinuation of a strong inducer. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Secukinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Secukinumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. A pharmacokinetic study with midazolam showed secukinumab is unlikely to affect drugs metabolized by CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sarilumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sarilumab is an IL-6 receptor monoclonal antibody and likely undergoes elimination via binding to its target antigen. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with sarilumab may have elevated levels of IL-6 which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Sarilumab will normalize cytochrome activity (via inhibition of IL-6) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing sarilumab. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ixekizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ixekizumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. A pharmacokinetic study with midazolam showed ixekizumab is unlikely to affect drugs metabolized by CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Golimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Golimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with golimumab may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Golimumab will normalize cytochrome activity (via reduction of cytokines) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing golimumab. Lamivudine is eliminated renally.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Enasidenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Enasidenib is metabolized by multiple CYP and UGTs enzymes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Enasidenib inhibits UGT1A1 but induces CYP3A4 and may decrease dolutegravir exposure although to a moderate extent as CYP3A4 does not play a major role in dolutegravir metabolism. No a priori dosage adjustment is required. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cobimetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce drug metabolizing enzymes. No interaction is expected with lamivudine. Cobimetinib is unlikely to have a clinically relevant effect on CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Daratumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fosfomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosfomycin is excreted unchanged mainly via the kidney by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ipilimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ipilimumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Olaparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olaparib is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Olaparib inhibited UGT1A1 in vitro, however, PBPK simulations suggest this is not of clinical importance. Olaparib is predicted to be a weak inhibitor of CYP3A4 in vivo and is not expected to have a clinically relevant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pembrolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pembrolizumab is an IgG4-kappa monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No metabolic drug interactions are expected with pembrolizumab.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Amivantamab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Fulvestrant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of fulvestrant has not been fully evaluated: in vitro studies suggest the involvement of CYP3A4, however, non-P450 routes appear to be more predominant in vivo. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4, and does not inhibit or induce CYP3A4. Lamivudine is eliminated renally. Fulvestrant does not inhibit CYP enzymes and there are no known drug-drug interactions.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ruxolitinib (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ruxolitinib is metabolized by CYP3A4 (major) and CYP2C9 (minor), and does not inhibit or induce CYPs. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Daptomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daptomycin is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Binimetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce UGTs or CYPs at clinically relevant concentrations. Lamivudine is eliminated renally. Binimetinib is unlikely to affect CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Panitumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Panitumumab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No drug interactions are expected with panitumumab.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Idelalisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Idelalisib is metabolised primarily by aldehyde oxidase, and to a lesser extent by CYP3A4 and UGT1A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. The primary metabolite of idelalisib, GS-563117, is a strong CYP3A4 inhibitor but is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pizotifen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pizotifen is glucuronidated by UGT2B10. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Pizotifen is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Cabotegravir [oral] (CAB oral)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Capmatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capmatinib is primarily metabolized by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Capmatinib is unlikely to have a clinically relevant effect on CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dexamethasone (low dose; 16 mg or less)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Omega-3 fatty acids [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Omega-3 fatty acids are eliminated via oxidation similar to dietary fatty acids. No interaction is expected with lamivudine. A pharmacokinetic interaction is unlikely with dolutegravir and omega-3 fatty acids alone. However, omega-3 fatty acids administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Description:

Coadministration of multivitamins (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and multivitamins can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) administered simultaneously decreased dolutegravir Cmax, AUC and Ctrough by 35%, 33% and 32%, respectively. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Apalutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Apalutamide can induce UGT1A1. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Coadministration is expected to decrease dolutegravir concentrations, thus dolutegravir should be administered at 50 mg twice daily in the absence of integrase class resistance. In the presence of integrase class resistance this combination should be avoided. Apalutamide has a long half-life (3 days), therefore the dolutegravir dose should be kept at 50 mg twice daily for a minimum of 2 weeks (but preferably 4 weeks) following cessation of enzalutamide due to the persisting inducing effect upon discontinuation of a strong inducer. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Rivastigmine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivastigmine is extensively metabolised by cholinesterase-mediated hydrolysis with minimal involvement of CYP450 enzymes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Rivastigmine is not expected to affect drugs metabolised by CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Galantamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Galantamine is metabolised mainly by CYP2D6 and CYP3A4, but is also glucuronidated and excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Galantamine is unlikely to have a clinically relevant effect on drugs metabolized by CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Opipramol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Opipramol is metabolized by CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYPs. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Enfortumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enfortumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism. MMAE is a substrate of CYP3A4 (and possibly CYP2D6) and P-gp. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Abatacept

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alirocumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alirocumab is a monoclonal antibody eliminated through binding to PCSK9 at low concentrations and through a proteolytic pathway at higher concentrations.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Brentuximab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with dolutegravir. MMAE is a substrate of CYP3A4 and P-gp but no interaction is expected as dolutegravir has no inhibitory or inducing effects on CYPs and brentuximab vedotin has no inhibitory or inducing effects on CYP3A4 or UGT1A1. Brentuximab vedotin does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dapoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapoxetine is metabolized by CYP2D6, CYP3A4 and flavin monooxygenase 1 whereas dolutegravir is mainly metabolized by UGT1A1. Dolutegravir has no inhibitory effects on CYP enzymes. Lamivudine does not interfere with dapoxetine metabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trametinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trametinib is mainly metabolised by deacetylation; metabolism by CYP3A4 is considered to be a minor pathway. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Trametinib is not expected to have a clinically significant effect on CYP3A4 or UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tecovirimat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tecovirimat is metabolized by hydrolysis (major) and glucuronidation by UGT1A1 and UGT1A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Tecovirimat is a weak inducer of CYP3A4 but is unlikely to cause a significant decrease in dolutegravir exposure as CYP3A4 is a minor route of dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Brincidofovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Dolutegravir and lamivudine do not affect this pathway.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Hyoscine butylbromide (Butylscopolamine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine butylbromide has poor systemic absorption and acts locally in the intestine. The main metabolic pathway is the hydrolytic cleavage of the ester bond. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Osimertinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Osimertinib is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Osimertinib is an inhibitor of CYP3A4 in vitro, but clinically significant interactions with drugs metabolised by CYP3A4 are not expected. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Regorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Regorafenib is metabolized by CYP3A4 and UGT1A9. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. O Regorafenib is unlikely to have a significant effect on CYP3A4 at clinically relevant concentrations. Regorafenib and its metabolites inhibit UGT1A1 and could increase dolutegravir exposure, although to a modest extent. No dose adjustment is needed. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Iron supplements (infusion/injection)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Integrase inhibitors are unlikely to be affected by chelation when iron supplements are administered as an injection or infusion. Administering iron at least 3 hours after dolutegravir/lamivudine would eliminate any possible risk of chelation as dolutegravir maximum plasma concentrations occur 2-3 hours post dose. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Apremilast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4, however, apremilast has no inhibitory or inducing effects on drug metabolizing enzymes or drug transporters. Lamivudine does not interfere with apremilast’s elimination pathways. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Norgestimate (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with norgestimate as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is deacetylated to the active metabolite norelgestromin which is then metabolised to norgestrel, possibly by CYP3A4. Dolutegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Guggulsterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized UGT1A1 and to a lesser extent by CYP3A4. In vitro studies suggest that guggulsterone activates PXR and therefore has the potential to induce CYP3A4 metabolism. A case report described sub-therapeutic elvitegravir/cobicistat concentrations in a HIV-infected individual with concomitant use of guggulsterone supplements who was subsequently switched to a dolutegravir containing regimen while continuing the use of guggulsterone. Dolutegravir concentrations were in the range of expected concentrations suggesting that metabolism by UGT may not be impacted by guggulsterone. No effect is expected on lamivudine as it is not metabolized by CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ponatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ponatinib is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8, CYP2D6 and CYP3A5. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Ponatinib does not affect CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tobramycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tobramycin is not metabolised and is primarily eliminated unchanged by glomerular filtration. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Selegiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selegiline is metabolised mainly by CYP2B6 with some contribution from CYP3A4 and CYP2A6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Selegiline is unlikely to affect UGT1A1 or CYP3A4. Dolutegravir does not inhibit or induce CYP2B6, CYP3A4 or CYP2A6. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Durvalumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Durvalumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Frovatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Frovatriptan is metabolized by CYP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Frovatriptan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Activated charcoal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and dolutegravir/lamivudine should be separated by 4 hours. [Note: this interaction is not specific for dolutegravir/lamivudine, but for any oral medication taken with activated charcoal.]

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Semaglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Semaglutide is metabolized by the enzyme neutral endopeptidase. Semaglutide (oral and injectable) delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, based on available interaction studies, a clinically relevant effect is not expected with dolutegravir or lamivudine. Note: food, beverages and oral medicinal products can interfere with the absorption of oral semaglutide. Therefore, patients must wait at least 30 minutes after taking oral semaglutide before taking any other oral medicinal product.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pertuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pertuzumab is an IgG1 monoclonal antibody and is eliminated via intracellular catabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. No metabolic drug interactions are expected with pertuzumab.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Favipiravir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Favipiravir undergoes no CYP-mediated metabolism but is mainly metabolised by aldehyde oxidase with UGT having a minor role. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A whereas lamivudine is eliminated renally. Favipiravir does not affect CYP3A4 or UGTs. Although favipiravir is a moderate inhibitor of OAT1, inhibition of this renal transporter does not impact the elimination of lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Maribavir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maribavir is primarily eliminated by CYP3A4 (at least 35%), with secondary contribution from CYP1A2 (no more than 25%), and some contribution from multiple UGTs (low). Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A whereas lamivudine is eliminated renally. Dolutegravir does not inhibit or induce CYP3A4. Maribavir is unlikely to have a clinically significant effect on UGTs or CYP3A.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Cenobamate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater could potentially decrease dolutegravir concentrations. If coadministration with cenobamate at doses of 200 mg daily or greater is necessary, a dose adjustment of dolutegravir to 50 mg twice daily is recommended in the absence of integrase class resistance. This dose adjustment should be maintained for approximately 2 weeks after stopping cenobamate as the inducing effect may persist after discontinuation of a strong inducer. In the presence of integrase class resistance this combination should be avoided. Cenobamate inhibits OAT3 but this does not impact lamivudine elimination.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dronedarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dronedarone is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. No significant interaction is expected with dolutegravir given that CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bempedoic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. Dolutegravir is mainly metabolized by UGT1A1. Bempedoic acid does not inhibit or induce UGTs. No interaction is expected with lamivudine

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Icosapent ethyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Icosapent ethyl is eliminated via beta-oxidation similar to dietary fatty acids.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tirzepatide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tirzepatide is metabolized by proteolytic cleavage. Tirzepatide delays gastric emptying, and has the potential to impact the absorption of concomitantly administered oral medications. However, based on available interaction studies, a clinically relevant effect is not expected with dolutegravir and lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Omega-3 fatty acids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omega-3 fatty acids are eliminated via oxidation similar to dietary fatty acids.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Afatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Afatinib is mainly eliminated unchanged in the faeces and does not inhibit or induce UGTs or CYP3A4. Dolutegravir is metabolized mainly by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alpelisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Abrocitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abrocitinib is mainly metabolized by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Abrocitinib is not expected to have a clinically relevant effect on UGTs or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Idarubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Idarubicin is converted to idarubicinol by aldo-keto reductase. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect idarubicin metabolism. Idarubicin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Furazolidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furazolidone is primarily metabolised by nitro-reduction to an aminofuran derivative. Detoxification and subsequent renal excretion occur mainly via glutathione conjugation. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Furazolidone is unlikely to affect UGT1A1 or CYP3A4. Dolutegravir is unlikely to affect furazolidone metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Doxylamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolised primarily by CYP2D6, CYP1A2 and CYP2C9. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Lamivudine is eliminated renally. Doxylamine is unlikely to have a clinically significant effect on dolutegravir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Sodium zirconium cyclosilicate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium zirconium cyclosilicate is not absorbed or metabolised by the body and is eliminated via the faeces. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Sodium zirconium cyclosilicate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pentosan polysulfate sodium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pentosan polysulfate sodium is metabolised by desulfation in the liver and depolymerisation in the kidney. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Pentosan polysulfate sodium is unlikely to affect UGT1A1 or CYP3A4. Metabolic drug-drug interactions are not expected with desulfation and depolymerisation reactions. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Guselkumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Guselkumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. In drug interaction studies, guselkumab had no clinically relevant effect on CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Entacapone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entacapone undergoes isomerization followed by glucuronidation of both the E and Z isomers; ~90% of the dose is then excreted in faeces. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Entacapone does not inhibit or induce UGT1A1 or CYP3A4. Dolutegravir does not inhibit or induce UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Deflazacort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Deflazacort and 21-desdeflazacort do not inhibit or induce UGT1A1 or CYP3A4. Dolutegravir does not inhibit or induce CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Daridorexant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daridorexant is mainly metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Daridorexant is unlikely to have a significant effect on UGT1A1. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir as CYP3A4 plays a minor role in dolutegravir metabolism. Dolutegravir does not inhibit or induce CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bimekizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bilastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Bilastine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lenacapavir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine.

Description:

If Sunlenca is discontinued, residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods. These concentrations are not expected to affect the exposures of other antiretroviral agents that are initiated after discontinuation of Sunlenca.

Sunlenca Summary of Product Characteristics, Gilead Sciences Ltd, August 2022.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alprostadil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Alprostadil is unlikely to affect CYP or UGT enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tivozanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tivozanib is metabolised mainly by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Tivozanib is unlikely to affect drugs metabolized by CYPs or UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Rucaparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Rucaparib is primarily metabolised by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Rucaparib is a weak inhibitor of CYP3A4 and UGT1A1 and could increase dolutegravir exposure, although to a modest extent. No dose adjustment is needed. Lamivudine is eliminated renally by OCT2, MATE1 and MATE2-k transporters. Rucaparib is a potent inhibitor of MATE1 and MATE2-K, and a weak inhibitor of OCT2. Coadministration may increase lamivudine concentrations but a clinically relevant interaction is not expected given the good tolerability of lamivudine and no a priori dose adjustment of lamivudine is needed.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cabergoline (lactation suppression)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Brimonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brimonidine is metabolized mainly by aldehyde oxidase.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cabergoline (Parkinson's disease)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Eletriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eletriptan is metabolised by CYP3A4 and does not induce or inhibit CYPs.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Riboflavin (Vitamin B2) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Retinol (Vitamin A) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Phytomenadione (Vitamin K) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of phytomenadione is thought to involve CYP4F2 and glucuronidation, but as glucuronidation is not the sole route of elimination, there is little potential for an interaction with dolutegravir via competition for glucuronidation pathways. Renal elimination of phytomenadione is minimal, therefore, there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Ferrous fumarate

Quality of Evidence: Very Low

Summary:

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. When taken with food, Dovato and ferrous fumarate can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking ferrous fumarate.

Description:

Coadministration of iron supplements (fasted intake) decreased dolutegravir AUC, Cmax and C24 by 54%, 57% and 56%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir during fasted conditions. In fed state, the changes in exposure following intake together with iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state. When taken with food, Dovato and supplements or multivitamins containing iron can be taken at the same time. If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Coadministration may decrease dolutegravir concentrations. Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and56%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. When taken with food, Dovato and supplements containing iron can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing iron.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=11) decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and 56%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir (n=10) decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. Dolutegravir and iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after iron supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Alectinib does not inhibit or induce CYP3A4 to a clinically relevant extent. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Iodine [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iodine is converted to iodide, which is trapped in the thyroid gland. Iodides are excreted mainly in the urine with smaller amounts excreted in the faeces, sweat and saliva.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Colecalciferol (Vitamin D3) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for an interaction with dolutegravir/lamivudine via modulation of, or competition for, metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Filgrastim

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Filgrastim is eliminated mainly by neutrophil-mediated clearance and renal excretion.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trastuzumab emtansine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trastuzumab emtansine is a monoclonal antibody-drug conjugate. Trastuzumab does not undergo CYP mediated metabolism, whereas DM1 (an active component of emtansine) is metabolized by CYP3A4. Dolutegravir does not inhibit or induce CYPs. Lamivudine does not interfere with trastuzumab emtansine elimination.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tixagevimab/ Cilgavimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A; lamivudine is eliminated renally. Tixagevimab and cilgavimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Tixagevimab and cilgavimab are not renally excreted or metabolized by CYP enzymes. Interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cabotegravir PrEP [long acting] (CAB LA, PrEP)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dolutegravir is mainly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes. No interaction is expected with lamivudine. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

Description:

Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of Apretude.

Apretude Prescribing Information, ViiV Healthcare, December 2021.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Carfilzomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolized, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs or UGT1A1. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Lorlatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorlatinib is primarily metabolised by CYP3A4 and UGT1A4 and, to a lesser extent, by CYP2C8, CYP2C19, CYP3A5 and UGT1A3. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Lorlatinib is a moderate inducer of CYP3A4 and a weak inducer of UGTs. Lorlatinib is unlikely to significantly alter dolutegravir exposure given that CYP3A4 plays a minor role in dolutegravir metabolism. No dose adjustment is required for medicinal products that are mainly metabolised by UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Molnupiravir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A; lamivudine is eliminated renally. Molnupiravir is rapidly metabolized by esterases to a nucleoside metabolite which is phosphorylated to an active triphosphate. Molnupiravir does not inhibit or induce CYPs and is unlikely to have significant drug-drug interactions with other therapies.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cabozantinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabozantinib is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4. Cabozantinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cabazitaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4, however, cabazitaxel has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Acalabrutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4. Acalabrutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Thiamine (Vitamin B1) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

Do Not Coadminister

Dolutegravir/Lamivudine (DTG/3TC)

Rilpivirine/ Emtricitabine/Tenofovir-DF (RPV/FTC/TDF)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) and Eviplera/Complera (rilpivirine, emtricitabine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine.

Description:

Due to similarities with emtricitabine, Eviplera should not be administered concomitantly with other cytidine analogues, such as lamivudine.

Eviplera Summary of Product Information, Gilead Sciences Ltd, August 2021.

Because Complera is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

Complera US Prescribing Information, Gilead Sciences Inc, November 2019.

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions.

Dovato Summary of Product Characteristics, ViiV Healthcare, July 2019.

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Avapritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYPs at clinically relevant concentrations. Avapritinib was shown to inhibit and induce CYP3A4 in vitro but the net effect in vivo has not been studied. However, avapritinib is unlikely to cause a significant effect on dolutegravir given that CYP3A4 is a minor pathway. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Axitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir does not inhibit or induce CYPs or UGTs at clinically relevant concentrations. No interaction is expected with lamivudine. Axitinib does not inhibit or induce UGTs or CYP3A4.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bosutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4. Bosutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tildrakizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tildrakizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. In a drug-drug interaction study, tildrakizumab had no clinically relevant effect on CYP enzymes. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isatuximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isatuximab is a IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Epcoritamab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epcoritamab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Emicizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Emicizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nicotinamide (Niacinamide) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is metabolized by nicotinamide methyltransferase to N-methylnicotinamide which is then metabolized by xanthine oxidase and aldehyde oxidase. Renal elimination of unchanged nicotinamide is minimal. No interaction is expected with dolutegravir and there is little potential for an interaction with lamivudine via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trastuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trastuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Inclisiran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inclisiran is primarily metabolised by nucleases and drug-drug interactions are not anticipated. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Inclisiran does not inhibit or induce CYPs or common drug transporters. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Relugolix

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Relugolix is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C8 and is a substrate of P-gp. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir has no inducing effects on CYPs. Relugolix is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Abemaciclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 and to a lesser extent CYP3A4. Abemaciclib has no inhibitory or inducing effects on drug metabolizing enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glucosamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glucosamine has been reported to undergo metabolism in the liver, but the metabolic pathway remains unclear. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Glucosamine does not affect CYPs and is unlikely to affect UGT1A1. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Finerenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finerenone is metabolized mainly by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Finerenone is not expected to have a clinically relevant effect on CYP3A4 or UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Pitolisant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitolisant is primarily metabolised by CYP2D6 and to a lesser extent by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Pitolisant is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Calcitonin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolized via proteolysis in the kidney. Dolutegravir and lamivudine do not interfere with this pathway.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Avelumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Clotrimazole (pessary, troche)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clotrimazole undergoes hepatic metabolism (likely via CYP3A4) and is a moderate inhibitor of CYP3A4. Coadministration is unlikely to alter clotrimazole exposure and no effect is expected on dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism. Lamivudine is unlikely to be impacted by clotrimazole.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mucuna pruriens

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on very limited data for metabolism and clearance, a clinically significant interaction is unlikely. No pharmacokinetic interactions have been reported with Mucuna pruriens.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metamizole is a pro-drug that undergoes hydrolysis to 4-methylaminoantipyrine (MAA) which is then metabolised by CYPs 3A4, 2B6, 2C8 and 2C9. Dolutegravir is metabolized by UGT1A1 and to a lesser extent by CYP3A4, and does not inhibit or induce CYP enzymes. Metamizole is a moderate inducer of CYP3A4 but is unlikely to cause a clinically significant reduction of dolutegravir based on the interaction study with rifabutin, another moderate inducer. No interaction is expected with lamivudine .

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Green tea extracts (Camellia sinensis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Green tea extracts weakly inhibit UGT1A1 in vitro and are unlikely to cause a clinically relevant interaction with dolutegravir. Although green tea extracts inhibited OCT2 in vitro, a clinically significant effect on lamivudine is unlikely as lamivudine has a large therapeutic index.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ginseng (Panax ginseng, Panax quinquefolis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on dolutegravir is expected as in vitro studies suggest Asian ginseng (Panax ginseng) is unlikely to affect UGT1A1 at clinically relevant concentrations. No effect on lamivudine is expected. No interaction is expected with American ginseng (Panax quinquefolius).

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Desvenlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is mainly metabolized by glucuronidation and to a minor extent through oxidative metabolism by CYP3A4 and CYP2C19. Renal elimination of unchanged desvenlafaxine also constitutes an important route of elimination. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. Desvenlafaxine is not expected to significantly inhibit or induce CYP3A4 at the dose in clinical use.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ayahuasca

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. In vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, but CYP3A4 does not play a major role in dolutegravir metabolism. No effect on lamivudine is expected.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Ashwagandha (Withania somnifera)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Isavuconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isavuconazole is metabolised by CYP3A4/5 and UGTs and is a moderate inhibitor of CYP3A4. No significant effect on dolutegravir exposure is expected as CYP3A4 plays a minor role in its metabolism. Lamivudine does not interact with isavuconazole’s metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Donepezil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Dolutegravir and lamivudine do not interact with this metabolic pathway.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Memantine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Memantine is eliminated by active renal secretion via OCT2 and MATE1. Dolutegravir inhibits OCT2 and MATE1 and may increase memantine exposure. Consider reducing memantine dosage in case of adverse effects. Memantine inhibits weakly OCT2 but this is unlikely to cause a clinically significant increase in exposure of lamivudine, an OCT2 substrate.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bazedoxifene

Quality of Evidence: Very Low

Summary:

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Dolutegravir does not inhibit or induce drug metabolizing enzymes. Lamivudine does not interact with these metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tibolone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with tibolone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tibolone is metabolized by several enzymatic pathways with no major involvement of CYP450. Dolutegravir and lamivudine do not interact with these metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Progesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with progesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Progesterone is metabolized by CYP3A4. Dolutegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atomoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolized by CYP2D6. Dolutegravir does not inhibit or induce CYP enzymes. Atomoxetine does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Silodosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Silodosin is metabolized by CYP3A4, UGT2B7, as well as alcohol and aldehyde dehydrogenase. Dolutegravir and lamivudine do not interfere with these pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Letermovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Letermovir is partly eliminated by glucuronidation via UGT1A1/3, but is largely eliminated unchanged in the bile. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. The effect of letermovir on UGT1A1 is unclear; the product label mentions it could potentially increase or decrease exposure of UGT1A1 substrates. However, inhibition of UGT1A1 would not require a dosage adjustment of dolutegravir based on the drug-drug interaction study with atazanavir. Furthermore, no dosage adjustment of dolutegravir would be needed if letermovir has a moderate inducing effect of UGT1A1. Letermovir does not affect lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dapivirine (DPV, PrEP)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly glucuronidated by UGT1A1. Lamivudine is eliminated renally. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Alogliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Furthermore, alogliptin was shown to be neither a substrate nor an inhibitor of the renal transporter OCT2.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Blinatumomab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tisotumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tisotumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with dolutegravir. MMAE is a substrate of CYP3A4 and P-gp but no interaction is expected as dolutegravir does not inhibit or induce CYPs and tisotumab vedotin does not inhibit or induce CYP3A4 or UGT1A1. Tisotumab vedotin does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Psilocybin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Psilocybin is rapidly dephosphorylated to psilocin which is responsible for the hallucinogenic effects. Psilocin is deactivated to multiple metabolites by alcohol dehydrogenase and monoamine oxidase or glucuronidated to psilocin-O-glucuronide by UGT1A9 in the liver or UGT1A10 in the small intestine before excretion in the urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect psilocybin or psilocin metabolism. Psilocybin and psilocin are unlikely to affect UGT1A1 or CYP3A4. No interactions are expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Teicoplanin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Teicoplanin is primarily excreted via urine as unchanged drug. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Safinamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Safinamide is metabolised by high-capacity amidases which are yet to be fully characterised, CYP enzymes are unlikely to be involved. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect safinamide metabolism. Safinamide is unlikely to inhibit or induce UGT1A1 or CYP3A4 at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Moclobemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moclobemide is metabolised via multiple pathways, including in part by CYP2C19 and CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect moclobemide metabolism. Moclobemide is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nitazenes

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitazenes are a family of synthetic opioids with a potency several hundred times stronger than morphine. Little is known about nitazene metabolism but it is likely to involve CYP metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. One member of the nitazene family (etazene) demonstrated potential to inhibit CYP3A4 in silico but a clinically significant effect is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tenapanor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenapanor is minimally absorbed following oral administration and is eliminated mainly unchanged in the faeces. Limited metabolism to M1, an inactive metabolite, occurs by primarily by CYP3A4/5. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Tenapanor is not expected to have a significant effect on drugs metabolized by CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Phentermine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phentermine is not extensively metabolised with 70-80% of an oral dose eliminated primarily unchanged in urine. In vitro studies indicate that CYP3A4 is the primary enzyme responsible for the limited metabolism of phentermine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Phentermine does not inhibit or induce CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tepotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tepotinib is metabolized by CYP3A4 and CYP2C8. No single metabolic pathway accounted for more than 25% of tepotinib elimination. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Tepotinib is unlikely to have a clinically significant effect on UGT1A1 or CYP3A4. Dolutegravir does not inhibit or induce CYP3A4 or CYP2C8. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cefuroxime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cariprazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Glasdegib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glasdegib is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C8 and UGT1A9. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Glasdegib does not inhibit or induce CYP enzymes and is unlikely to have a clinically significant effect on UGTs. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Riluzole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Riluzole is mainly metabolized by CYP1A2 and the major active metabolite is then glucuronidated. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Mitomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mitomycin is hepatically metabolised but the enzymes involved are unclear; modulation of CYP450 is unlikely to be significant. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect mitomycin metabolism. Mitomycin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Minocycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minocycline is almost completely absorbed with one third excreted as unchanged drug. Unlike other tetracyclines, there is evidence that partial metabolism by CYPs (including CYP3A4) occurs. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir is unlikely to affect minocycline concentrations. Minocycline is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Dexketoprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Dolutegravir does not inhibit or induce UGTs or CYP2C8/9. Dexketoprofen is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bromocriptine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine is eliminated renally. Bromocriptine is unlikely to affect UGT1A1 or CYP3A4. Dolutegravir does not inhibit or induce CYP3A4. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Triamterene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamterene is mainly metabolized by CYP1A2. Dolutegravir does not inhibit or induce CYP1A2. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Bulevirtide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bulevirtide is catabolized by peptidases and elimination occurs through binding to NTCP (a bile salt liver transporter serving as HDV/HBV entry receptor). Dolutegravir and lamivudine do not interfere with this elimination pathway.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Febuxostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Febuxostat is extensively metabolized by multiple UGT enzymes (UGTs 1A1, 1A3, 1A8, 1A9 and 2B7) and CYP enzymes (CYPs 1A1, 1A2, 2C8 and 2C9). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Febuxostat is not expected to have a clinically significant effect on CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Atogepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atogepant is metabolized primarily by CYP3A4 and is a substrate of OATP. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYP enzymes. Atogepant is not expected to have a clinically relevant effect on drugs metabolized by CYP or UGT enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Tocopherol (Vitamin E) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Certolizumab pegol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Patients requiring treatment with certolizumab pegol may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Certolizumab pegol will normalize cytochrome activity (via reduction of cytokines) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing certolizumab pegol. Lamivudine is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Nefopam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nefopam undergoes extensive hepatic metabolism and both unchanged nefopam and metabolites are excreted principally in the urine. Limited data suggest that CYP and UGT enzymes may have a role in the metabolism of nefopam. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Nefopam is unlikely to have a clinically significant effect on dolutegravir. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Brexpiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Brexpiprazole is unlikely to have a clinically relevant effect on drugs metabolised by CYP enzymes. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Trenbolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trenbolone is mainly excreted in urine as glucuronide conjugates. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Trenbolone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Oxymetholone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxymetholone undergoes oxidation, reduction and hydroxylation; CYP enzymes are unlikely to be involved. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Oxymetholone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Collagen hydrolysate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Collagen hydrolysate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Chlormadinone (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Ethinylestradiol is mainly metabolized by hydroxylation and glucuronidation. Dolutegravir does not interact with these metabolic pathways. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. No interaction is expected with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Polatuzumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Polatuzumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with dolutegravir. MMAE is a substrate of CYP3A4 and P-gp but no interaction is expected as dolutegravir has no inhibitory or inducing effects on CYPs and polatuzumab vedotin has no inhibitory or inducing effects on CYP3A4 or UGT1A1. Polatuzumab vedotin does not interact with lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Abiraterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Dolutegravir and lamivudine do not interact with these metabolic pathways.

Description:

(See Summary)

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Enteral Feeds

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Enteral feeds contain polyvalent cations. Dolutegravir concentrations may decrease due to chelation with polyvalent cations. Where possible, a break in enteral feeding is advised for 6 hours before and 2 hours after taking dolutegravir. No interaction is expected with lamivudine.

Description:

Coadministration may decrease dolutegravir concentrations. Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

Potential Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Oral nutritional supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Oral nutritional supplements contain polyvalent cations. Dolutegravir concentrations may decrease due to chelation with polyvalent cations. Dolutegravir should be administered at least 2 hours before or 6 hours after oral nutritional supplements. No interaction is expected with lamivudine.

Description:

Coadministration may decrease dolutegravir concentrations. Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.

Dovato US Prescribing Information, ViiV Healthcare, April 2019.

No Interaction Expected

Dolutegravir/Lamivudine (DTG/3TC)

Cedazuridine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Cedazuridine does not inhibit or induce CYP enzymes. No interaction is expected with lamivudine which is eliminated renally.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Decitabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Phosphorylation of lamivudine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Decitabine does not inhibit or induce CYP enzymes.

Description:

(See Summary)

Potential Weak Interaction

Dolutegravir/Lamivudine (DTG/3TC)

Azacitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Phosphorylation of lamivudine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Azacitidine does not inhibit or induce CYP enzymes

Description:

(See Summary)