Juluca (dolutegravir/rilpivirine) 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 abacavir would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (exact transporter unknown, possibly OATs or OCTs).

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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. In vitro data suggest that dolutegravir inhibits OCT2 therefore a drug-drug interaction is unlikely as those drugs act on different renal transporters. Rilpivirine does not interfere with acetazolamide elimination.

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. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation.

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.

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.

Coadministration has not been studied but based on 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. Rilpivirine does not interact with this elimination pathway.

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). Dolutegravir and rilpivirine do not interfere with this metabolic pathway.

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 and rilpivirine. Therapeutic drug monitoring of dolutegravir and rilpivirine is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Juluca (dolutegravir/rilpivirine) 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. Rilpivirine is metabolized primarily by CYP3A with potential contribution from CYP2C19. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. 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.

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. No a priori clinically relevant drug-drug interaction is anticipated.

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. Caution is advised as alcuronium has a narrow therapeutic window. Rilpivirine is unlikely to significantly inhibit alcuronium renal elimination.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes CYP3A4 metabolism. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Alfuzosin is metabolised mainly by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. A clinically relevant effect on rilpivirine concentrations is unlikely as alfuzosin does not inhibit CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with alfuzosin. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Alfuzosin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized by CYP but is a substrate of P-glycoprotein. Dolutegravir and rilpivirine do not inhibit or induce P-glycoprotein in the range of clinically relevant concentrations.

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. Dolutegravir and rilpivirine do not interfere with this metabolic pathway.

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).

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.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant 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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. Rilpivirine is unlikely to affect the renal elimination of amantadine. However, there is potential for dolutegravir to increase amantadine exposure via inhibition of OCT2 but the clinical relevance of this is unknown.

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 and rilpivirine do not interfere with ambrisentan metabolism.

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

Coadministration has not been studied. Amiloride is eliminated unchanged by the kidney with in vitro data indicating that it is a substrate of OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase amiloride exposure. Rilpivirine does not interfere with this elimination pathway.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied. Amiodarone is metabolized by CYP2C8 and CYP3A4; in vitro data suggest it is only a weak inhibitor of CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with amiodarone. However, given the QT prolongation risk associated with amiodarone, caution is recommended.

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. Rilpivirine does not interact with this elimination pathway.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amodiaquine is metabolized mainly by CYP2C8. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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. Dolutegravir is not expected to inhibit this renal transporter. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolized by CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ampicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. Renal clearance of ampicillin 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 60-80% is excreted in the urine within 6 hours. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with due to ampicillin’s large therapeutic index. Rilpivirine is unlikely to significantly inhibit ampicillin renal elimination.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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.

Coadministration with dolutegravir/rilpivirine has not been studied. Coadministration of dolutegravir with polyvalent cation-containing products such as antacids may lead to decreased absorption of dolutegravir. Simultaneous coadministration of a magnesium/aluminium containing antacid (Maalox) and dolutegravir (50 mg once daily, n=16) decreased dolutegravir Cmax, AUC and Ctrough by 72%, 74% and 74%, respectively. When antacid was administered 2 hours after dolutegravir (50 mg once daily, n=16), dolutegravir Cmax, AUC and Ctrough decreased by 18%, 26% and 30%, respectively. The combination of rilpivirine and antacids should be used with caution as co-administration may cause significant decreases in rilpivirine plasma concentrations due to an increase in gastric pH. Antacids should be taken well separated in time from the administration of Juluca (minimum 6 hours before or 4 hours after).

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

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with apomorphine. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Apomorphine has a possible risk of QTc prolongation on the CredibleMeds.org website. 

Coadministration has not been studied. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. However, aprepitant is a moderate inhibitor of CYP3A4 and could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. No interaction is expected with dolutegravir.

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. 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 rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with aripiprazole. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Aripiprazole has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYPs (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolised via UGT1A9 and UGT2B7. Artemisinins induce CYP3A4 and/or CYP2C19. Dolutegravir is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations and a clinically significant effect of rilpivirine on artemisinin is unlikely. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. However, artemisinins could potentially decrease rilpivirine concentrations, but this is unlikely to be clinically relevant due to the short treatment duration for artemisinins.

Coadministration with dolutegravir/rilpivirine 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 are rapidly excreted in the urine when in excess of the requirements of the body. No interaction is expected with rilpivirine. 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%. The combination of dolutegravir/rilpivirine and supplements should be used with particular caution. Multivitamins should be co-administered at the same time as dolutegravir/rilpivirine with a meal. If multivitamins cannot be taken at the same time as dolutegravir/rilpivirine, these supplements should be taken well separated in time from the administration of dolutegravir/rilpivirine (minimum 6 hours before or 4 hours after).

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). Dolutegravir and rilpivirine not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with asenapine. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Asenapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticulo endothelial system.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetylsalicylic acid is deacetylated to form salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6) which is further glucuronidated. Dolutegravir and rilpivirine are not expected to inhibit or induce UGTs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetylsalicylic acid Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6). Dolutegravir and rilpivirine are not expected to inhibit or induce UGTs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Astemizole is metabolized by CYP2D6, CYP2J2 and CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with astemizole. However, given the known QT prolongation risk associated with astemizole, caution is recommended.

Juluca (dolutegravir/rilpivirine) 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. Coadministration of atazanavir alone (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. Coadministration of rilpivirine and atazanavir has not been studied but may increase rilpivirine concentrations. Rilpivirine is not expected to affect concentrations of atazanavir. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir. However, the product labels for Juluca indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Atazanavir has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Juluca (dolutegravir/rilpivirine) 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. Coadministration with atazanavir/cobicistat has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold (due to inhibition of UGT1A1 by atazanavir). Similarly, co-administration with atazanavir/cobicistat is expected to increase dolutegravir plasma concentrations. Dolutegravir is not expected to affect the pharmacokinetics of atazanavir/cobicistat. Coadministration is expected to increase rilpivirine concentrations but is not expected to affect cobicistat concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir/cobicistat. However, the product labels for Juluca indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Atazanavir has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Juluca (dolutegravir/rilpivirine) 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. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. Coadministration of rilpivirine with atazanavir/ritonavir) has not been studied but may increase rilpivirine concentrations. Rilpivirine is not expected to affect concentrations of atazanavir. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir/ritonavir. However, the product labels for Juluca indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Atazanavir has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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. Therefore 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. Rilpivirine does not interfere with atenolol renal elimination. It is recommended to start atenolol at a lower dose and adjust dosage until the desired clinical effect is achieved.

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 CYP enzymes at clinically relevant concentrations. Coadministration of rilpivirine (150 mg once daily) and atorvastatin (40 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 9%, 10% and 10%, respectively. Atorvastatin Cmax and AUC increased by 35% and 4%; Cmin decreased by 15%. Cmax, AUC and Cmin of 2-hydroxy atorvastatin increased by 58%, 39% and 32%, whilst Cmax and AUC of 4-hydroxy atorvastatin increased by 28% and 23%. No dose adjustment is needed for either drug. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.]

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

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. There is, therefore, little potential for clinically significant interactions with dolutegravir or rilpivirine via modulation of, or competition for, metabolic pathways.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is further inactivated by xanthine oxidase and thiopurine methyltransferase to natural purines. Dolutegravir and rilpivirine do not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. Rilpivirine does not interfere with this elimination pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with azithromycin. However, given the known QT prolongation risk associated with azithromycin, caution is recommended.

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

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.

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 CYP, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate. Dolutegravir and rilpivirine does not interact with this metabolic pathway.

Coadministration has not been studied. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Concentrations are unlikely to be affected by dolutegravir. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with bedaquiline. However, bedaquiline has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website therefore caution is recommended. When bedaquiline is coadministered with other medicinal products that prolong the QTc interval, an additive or synergistic effect on QT prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including frequent electrocardiogram assessment is recommended. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents.

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.

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.

Coadministration has not been studied but based on 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 CYP enzymes. Similarly, dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine does not interfere with these pathways.

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

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. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with bepridil. However, given the known QT prolongation risk associated with bepridil, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4 but no effect on betamethasone is expected as dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Betamethasone is a moderate inducer of CYP3A4. Coadministration is unlikely to affect dolutegravir concentrations, but could significantly decrease rilpivirine concentrations particularly if betamethasone is administered orally or intravenously at high doses or for a long duration, in which case coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp; dolutegravir and rilpivirine do not inhibit or induce P-gp. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with betrixaban. However, the product labels for dolutegravir/rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Betrixaban has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

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.

Coadministration has not been studied. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300 mg/m2/day). Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. However, bexarotene could potentially decrease rilpivirine exposure. Perform TDM of rilpivirine if available.

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.

Juluca (dolutegravir/rilpivirine) 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. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

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

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.

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. There is no evidence that bisoprolol inhibits or induces CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 rilpivirine is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate)

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent CYP1A2, 2D6 and 2C9. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. A clinically relevant effect on rilpivirine concentrations is unlikely as bortezomib is a weak inhibitor of CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with bortezomib. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bortezomib has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. No effect om bosentan is expected as dolutegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Bosentan could potentially decrease dolutegravir exposure although to a moderate extent as CYP3A4 does not play a major role in dolutegravir metabolism and no a priori dosage adjustment of dolutegravir is required. Bosentan could potentially decrease rilpivirine exposure. Patients should be monitored carefully regarding their HIV infection.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is predominantly metabolized via CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration 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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. 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. No interaction is expected with rilpivirine.

Coadministration with dolutegravir/rilpivirine has not been studied. Calcium is eliminated through faeces, urine and sweat. 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. In addition, calcium supplements containing calcium carbonate may decrease rilpivirine concentrations due to reduced absorption due to gastric pH increase. The combination of dolutegravir/rilpivirine and supplements should be used with particular caution. Calcium supplements should be co-administered at the same time as dolutegravir/rilpivirine with a meal. If calcium supplements cannot be taken at the same time as dolutegravir/rilpivirine, these supplements should be taken well separated in time from the administration of dolutegravir/rilpivirine (minimum 6 hours before or 4 hours after).

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 which are not affected by dolutegravir or rilpivirine.

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

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 and rilpivirine do not inhibit or induce P450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetrahydrocannabinol (THC, the psychoactive component of cannabis), is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dolutegravir does not interfere with this metabolic pathway. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with capecitabine. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Capecitabine has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

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. Renal function should be monitored as clinically appropriate. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine (40-50% as unchanged drug, the rest as disulfide and other metabolites).

Coadministration is contraindicated as significant decreases in rilpivirine plasma concentrations may occur. 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. Coadministration with rilpivirine has not been studied but concentrations are expected to decrease due to induction of CYP3A by carbamazepine. 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.

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).

Coadministration has not been studied. 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. Thiamazole has been shown to have inhibitory effects on CYP3A4 in vitro, however, the clinical relevance of this for rilpivirine is unclear.

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 therefore there is little potential for a pharmacokinetic interaction.

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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

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. There is no evidence that dolutegravir inhibits OATP1B1. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied. Cat’s claw is an inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Similarly, concentrations of rilpivirine may also increase, but to a limited extent and no dose adjustment is required for rilpivirine. CYP3A4 does not play a major role in dolutegravir metabolism.

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 and rilpivirine are not expected to inhibit these renal transporters.

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 and rilpivirine are not expected to inhibit these renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 50% of the absorbed cefixime dose is excreted unchanged in the urine (predominantly by glomerular filtration); there is no evidence of metabolism of cefixime in vivo. In vitro studies have shown that cefixime does not inhibit/induce major cytochrome P450 metabolic enzymes and would not be expected to cause clinically significant interactions with other drugs, which are metabolized by CYP enzymes.

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 and rilpivirine are not expected to inhibit these renal transporters.

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.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is metabolised mainly by CYP2C9. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

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.

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. In vitro studies have shown that chlorambucil does not inhibit cytochrome P450 metabolic enzymes.

Coadministration has not been studied. 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. Coadministration may potentially increase levels of rilpivirine (due to CYP3A4 inhibition), increasing the risk of adverse events. The clinical significance of this interaction is unknown. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

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 but does not inhibit cytochromes. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with chloroquine. However, given the known QT prolongation risk associated with chloroquine, caution is recommended. Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine. ECG monitoring is advised. 

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with chlorpromazine. However, given the known QT prolongation risk associated with chlorpromazine, caution is recommended.

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

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/rilpivirine does not interact with ciclesonide metabolism.

Coadministration has not been studied. Ciclosporin inhibits CYP3A4 and OATP1B1. Ciclosporin is unlikely to affect dolutegravir but may increase rilpivirine exposure, but to a limited extent and no dose adjustment is required for rilpivirine.

Coadministration has not been studied but based on 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 and rilpivirine are not expected to inhibit these renal transporters.

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

Coadministration with dolutegravir/rilpivirine has not been studied. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. However, coadministration may reduce rilpivirine absorption due to gastric pH increase. The combination of dolutegravir/rilpivirine and H2-receptor antagonists should be used with particular caution. Only H2-receptor antagonists that can be dosed once daily should be used and should be taken at least 4 hours after or 12 hours before dolutegravir/rilpivirine.

Coadministration has not been studied. 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. Rilpivirine does not interfere with ciprofloxacin elimination. Ciprofloxacin is a moderate inhibitor of CYP3A4 and could increase rilpivirine exposure but to a limited extent and no dose adjustment is required for rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with ciprofloxacin. However, given the known QT prolongation risk associated with ciprofloxacin, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cisapride is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cisapride. However, given the known QT prolongation risk associated with cisapride, caution is recommended.

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).

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. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with citalopram. However, given the known QT prolongation risk associated with citalopram, caution is recommended.

Coadministration has not been studied. Clarithromycin is a strong inhibitor of CYP3A4. CYP3A4 does not play a major role in dolutegravir metabolism, but coadministration may increase rilpivirine concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clarithromycin. However, given the known QT prolongation risk associated with clarithromycin, caution is recommended. Consider alternatives such as azithromycin.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4 and some metabolites have antibacterial activity. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6, CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Clobazam is a weak inducer and could potentially decrease dolutegravir and rilpivirine exposure although to a limited extent.

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

Coadministration has not been studied. 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 via this mechanism is unlikely. Clofazimine is a moderate inhibitor of CYP3A4 and may increase rilpivirine concentrations but to a modest extent. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clofazimine. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clofazimine has a conditional risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

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 and rilpivirine do not inhibit OAT1. 

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. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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).

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with clozapine. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clozapine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.  Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cocaine. However, given the known QT prolongation risk associated with cocaine, caution is recommended.

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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is a substrate of CYP3A4. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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. Dolutegravir and rilpivirine do not interfere with this metabolic pathway. 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%. The combination of dolutegravir/rilpivirine and supplements should be used with particular caution. Multivitamins should be co-administered at the same time as dolutegravir/rilpivirine with a meal. If multivitamins cannot be taken at the same time as dolutegravir/rilpivirine, these supplements should be taken well separated in time from the administration of dolutegravir/rilpivirine (minimum 6 hours before or 4 hours after).

Coadministration has not been studied. There is no evidence to suggest that Piper cubeba impacts UGTs. However, several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro. A clinically significant interaction with dolutegravir is unlikely. Coadministration could potentially increase the exposure of rilpivirine, but to a limited extent and no dose adjustment is required for rilpivirine.

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with rilpivirine. No interaction is expected with dolutegravir and 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. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. The combination of dolutegravir/rilpivirine and supplements should be used with particular caution. Multivitamins should be co-administered at the same time as dolutegravir/rilpivirine with a meal. If multivitamins cannot be taken at the same time as dolutegravir/rilpivirine, these supplements should be taken well separated in time from the administration of dolutegravir/rilpivirine (minimum 6 hours before or 4 hours after).

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4 and does not inhibit CYPs when used at doses lower than 100 mg three times per day. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytarabine is metabolized by cytidine deaminase and dolutegravir does not interfere with this metabolic pathway.

Coadministration has not been studied. The prodrug of dabigatran is a substrate of P-gp. In vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. However, increases in dabigatran plasma concentrations due to inhibition of intestinal P-gp by rilpivirine cannot be excluded.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration with dolutegravir/rilpivirine has not been studied. 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 dose adjustment of daclatasvir or dolutegravir is required. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9 which is not affected by dolutegravir or rilpivirine.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Juluca (dolutegravir/rilpivirine) 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 Juluca 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. Coadministration of rilpivirine and darunavir/cobicistat is expected to increase plasma concentration of rilpivirine, but the expected increase in rilpivirine concentrations is not considered clinically relevant.

Juluca (dolutegravir/rilpivirine) and Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interactions are expected. 

Juluca (dolutegravir/rilpivirine) 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/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of darunavir/ritonavir (600/100 mg twice daily) and dolutegravir (30 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 11%, 22% and 38%, respectively. Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) was studied in 14 subjects. Rilpivirine Cmax increased by 79% and AUC and Cmin increased by 2.3- and 2.78-fold, respectively. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.]

Coadministration has not been studied. Dasatinib is metabolized by CYP3A4 and is a weak inhibitor of CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dasatinib could potentially increase rilpivirine exposure although to a moderate extent. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with dasatinib. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. An in vitro study has shown that daunorubicin was able to inhibit metabolism mediated by CYP3A4, but was unlikely to cause clinically significant drug interactions via this mechanism. Dolutegravir and rilpivirine do not interact with daunorubicin metabolic pathway. However, damage to the myocardium is one of the major risks of daunorubicin treatment and may include: dose-independent supraventricular arrhythmias (sinus tachycardia, premature ventricular contractions, AV-block) and/or non-specific ECG abnormalities.

Coadministration has not been studied. 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. No pharmacokinetic interaction is expected as dolutegravir and rilpivirine do not affect CYP enzymes. However, QTc prolongation has been reported with delamanid (and is very closely correlated with the metabolite DM-6705). Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with delamanid. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Delamanid has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway. (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.)

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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desipramine is metabolized by CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with desipramine. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied 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 CYP enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied 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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 2A6). Dolutegravir and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

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 CYP2C19) and to temazepam (mainly by CYP3A4). Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

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.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The elimination of digoxin is dependent on P-glycoprotein. In vitro data indicate that dolutegravir does not inhibit P-glycoprotein at clinically relevant concentrations. In a clinical study, coadministration of digoxin (0.5 mg single dose) and rilpivirine (25 mg once daily) had no significant effect on digoxin pharmacokinetics (Cmax increased by 6%, AUC decreased by 2%).

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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. 

Coadministration has not been studied. Dihydroergotamine is a substrate and inhibitor of CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Furthermore, a clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Dihydroergotamine could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine.

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.

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Diltiazem could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with diltiazem. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Diltiazem has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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 and rilpivirine do not inhibit or induce these UGTs.

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. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with disopyramide. However, given the known QT prolongation risk associated with disopyramide, caution is recommended.

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.

Coadministration has not been studied. Docetaxel is metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. However, some European product labels for docetaxel warn in vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which are metabolised by cytochrome P450 3A (and thus may inhibit the enzyme competitively). Caution should be exercised when treating patients with docetaxel and rilpivirine as concomitant therapy since there is a potential for a significant interaction.

Coadministration has not been studied and is contraindicated. 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. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with dofetilide. However, given the known QT prolongation risk associated with dofetilide, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a 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 and rilpivirine are not expected to inhibit or induce CYP and UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with dolasetron. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

The dolutegravir dose (50 mg) in Juluca may be insufficient when coadministered with some medications that may decrease dolutegravir concentrations. If additional dolutegravir is required, a dolutegravir 50 mg tablet, separated by 12 hours from Juluca could be taken.

Juluca (dolutegravir, rilpivirine) 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 Juluca and Triumeq contain dolutegravir and should not be taken with any other medicinal products also containing dolutegravir.

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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with domperidone. However, given the known QT prolongation risk associated with domperidone, caution is recommended.

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. There is little potential for dopamine to affect the disposition of antiretrovirals, or to be affected if co-administered with antiretrovirals.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, doravirine should not be administered with products containing another NNRTI (i.e. rilpivirine).

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Juluca (dolutegravir, rilpivirine 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, doravirine should not be administered with another NNRTI (i.e., rilpivirine).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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.) However, rilpivirine should be used with caution when coadministered with a drug that has a potential risk to prolong the QT interval. In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QT interval. Possible cardiac toxicities (ECG abnormalities and sometimes arrhythmias) have been reported with doxorubicin. Use with caution. ECG monitoring is recommended.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied. Dulaglutide is degraded by general protein catabolism pathways therefore no metabolic interaction is expected. Dulaglutide delays gastric emptying but interaction studies showed no clinically significant effect on the absorption of concomitantly orally administered drugs. No interaction is expected with dolutegravir. However, caution is needed when coadministering rilpivirine and GLP-1 agonists such as dulaglutide due to their potential to inhibit gastric secretion and thereby reduce the absorption of rilpivirine. Consider monitoring virological response after initiating dulaglutide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied. 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. Echinacea could potentially cause a modest reduction in rilpivirine plasma concentrations. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is a substrate for P-gp. Dolutegravir and rilpivirine do not inhibit or induce P-gp.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministration may decrease dolutegravir and rilpivirine concentrations and combining two NNRTIs (i.e., efavirenz and rilpivirine) has not been shown to be beneficial. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. Furthermore, rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with efavirenz. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Efavirenz has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eflornithine is predominantly eliminated unchanged via the kidneys. Dolutegravir and rilpivirine are unlikely to significantly inhibit eflornithine renal elimination.

Coadministration with dolutegravir/rilpivirine has not been studied. Coadministration of multiple doses of elbasvir/grazoprevir and dolutegravir or rilpivirine had no clinically relevant effect on the pharmacokinetics of grazoprevir, elbasvir, dolutegravir or rilpivirine. No dose adjustments are required. 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. Coadministration of rilpivirine (25 mg once daily) and elbasvir + grazoprevir (50 + 200 mg once daily) to 19 subjects increased elbasvir AUC, Cmax and C24 by 7%, 7% and 4%, respectively; grazoprevir AUC and Cmax decreased by 2% and 3%, with no change in C24. Rilpivirine AUC, Cmax and Ctrough increased by 13%, 7% and 16%, respectively.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Rilpivirine is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Juluca (dolutegravir/rilpivirine) 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. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Juluca (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. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

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 and rilpivirine are unlikely to affect the metabolism of empagliflozin. Empagliflozin is unlikely to affect dolutegravir or rilpivirine concentrations as it does not inhibit or induce CYPs and does not inhibit UGTs. In vivo data indicate that inhibition of P-gp by rilpivirine at a dose of 25 mg once daily is not clinically relevant.

Juluca (dolutegravir/rilpivirine) 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 emtricitabine would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected.

Juluca (dolutegravir/rilpivirine) 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 emtricitabine/tenofovir alafenamide would be possible from a pharmacokinetic standpoint. Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls. Coadministration of rilpivirine (25 mg once daily) and tenofovir alafenamide (25 mg once daily) had no significant effect on the pharmacokinetics of rilpivirine and tenofovir alafenamide. No interaction is expected with emtricitabine. When given with dolutegravir or rilpivirine, the recommended dose of Descovy (emtricitabine/tenofovir alafenamide) is 200/25 mg once daily.

Juluca (dolutegravir/rilpivirine) 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 emtricitabine/tenofovir-DF would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected.

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 and rilpivirine are not expected to inhibit OATs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enflurane is predominantly metabolized by CYP2E1. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

Coadministration has not been studied but based on 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. Rilpivirine does not interact with this elimination pathway.

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. Rilpivirine does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Dolutegravir and rilpivirine are not expected to inhibit or induce UGT enzymes at clinically relevant concentrations. Epirubicin may lead to cardiotoxicity consisting of tachycardia and/or ECG abnormalities. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with epirubicin. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Epirubicin has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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

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

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

Coadministration has not been studied. Ergotamine is a substrate and inhibitor of CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Ergotamine could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erlotinib is mainly metabolized by CYP3A4 and is a strong inhibitor of UGT1A1 in vitro. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Erlotinib could increase dolutegravir concentrations, however, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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.

Coadministration has not been studied. Erythromycin is considered to be a moderate inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Coadministration may increase rilpivirine concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur with erythromycin. However, given the known QT prolongation risk associated with erythromycin, caution is recommended. Consider alternatives such as azithromycin.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with escitalopram. However, given the known QT prolongation risk associated with escitalopram, caution is recommended.

Coadministration has not been studied and is not recommended. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4. Eslicarbazepine was shown to reduce simvastatin (CYP3A4 substrate) exposure by 50%. A similar effect is expected on rilpivirine, leading to loss of therapeutic effect and possible development of resistance. Dolutegravir exposure is also expected to be decreased. An alternative anticonvulsant should be considered. 

Coadministration has not been studied. Coadministration is contraindicated due to the potential for significant decreases in rilpivirine plasma concentrations due to gastric pH increase, which may result in loss of virologic response. 

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 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.

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.

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%).

Coadministration with dolutegravir/rilpivirine has not been studied. Coadministration of ethinylestradiol (0.035 mg) and dolutegravir (50 mg twice daily) had no clinically relevant effect on the pharmacokinetics of ethinylestradiol (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. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and an oral contraceptive containing ethinylestradiol/norethindrone (0.035/1.0 mg once daily) had no effect on rilpivirine Cmax, AUC and Cmin. Ethinylestradiol Cmax, AUC and Cmin increased by 17%, 14% and 9%: norethisterone Cmax, AUC and Cmin decreased by 6%, 11% and 1%. No dose adjustment is needed. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

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. Ethionamide does not affect metabolism mediated by CYP enzymes in vitro.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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

Coadministration of dolutegravir/rilpivirine 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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Coadministration of etonogestrel-containing progestogen-only implant (68 mg) in HIV-positive women on a rilpivirine-based regimen did not significantly alter etonogestrel concentrations (18% increase at week 24; 15% decrease at week 48) compared to HIV-negative women receiving the same contraceptive in the absence of antiretroviral therapy. The etonogestrel implant represents a suitable contraceptive option for women receiving rilpivirine-based antiretroviral regimens.

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 CYP enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC combined oral contraceptive containing ethinylestradiol/norgestimate. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministration may decrease dolutegravir and rilpivirine concentrations and combining two NNRTIs (i.e., etravirine and rilpivirine) has not been shown to be beneficial. Coadministration of etravirine (200 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 52%, 71% and 88%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of etravirine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eucalyptus is only a weak inhibitor of CYP3A4 and there is no evidence to suggest that it impacts UGTs. Coadministration is unlikely to impact the exposure of dolutegravir or rilpivirine.

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 is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied. Exenatide is primarily eliminated by glomerular filtration therefore no interaction is expected with dolutegravir or rilpivirine at the level of drug elimination. However, caution is needed when coadministering rilpivirine and GLP-1 agonists such as exenatide due to their potential to inhibit gastric secretion and thereby reduce the absorption of rilpivirine. Furthermore, exenatide has the potential to slow gastric emptying. Consider taking Juluca 4 hours before the GLP-1 agonist.

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 and rilpivirine are not expected to inhibit or induce UGTs at clinically relevant concentrations. 

Coadministration has not been studied but based on 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 and rilpivirine do not interfere with this elimination pathway.

Coadministration with dolutegravir/rilpivirine has not been studied. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. However, coadministration may reduce rilpivirine absorption due to gastric pH increase.  Coadministration of rilpivirine (150 mg single dose) and famotidine (40 mg single dose) administered 2 hours before rilpivirine, decreased rilpivirine Cmax and AUC by 85% and 76%. Coadministration of famotidine 12 hours before rilpivirine decreased rilpivirine Cmax and AUC by 1% and 9%; coadministration of famotidine 4 hours after rilpivirine increased rilpivirine Cmax and AUC by 21% and 13%. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.] The combination of dolutegravir/rilpivirine and H2-receptor antagonists should be used with particular caution. Only H2-receptor antagonists that can be dosed once daily should be used and should be taken at least 4 hours after or 12 hours before dolutegravir/rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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. In vivo data indicate that inhibition of P-gp by rilpivirine at a dose of 25 mg once daily is not clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolized by CYP3A4. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There are no data in humans, but fish oil inhibited CYP3A-mediated metabolism of saquinavir in rat liver microsomes. Simultaneous coadministration with saquinavir in rats increased saquinavir exposure by ~3-fold. Separating the doses by 2 h overcame the interaction.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with flecainide. However, given the known QT prolongation risk associated with flecainide, caution is recommended. Consider alternatives.

Coadministration has not been studied. Flibanserin is primarily metabolized by CYP3A4 and has been shown to moderately increase the exposure of simvastatin, a CYP3A4 substrate. Coadministration is unlikely to increase dolutegravir exposure to a significant extent as CYP3A4 plays a minor role in dolutegravir metabolism. However, coadministration could potentially increase rilpivirine exposure, but to a limited extent and no dose adjustment is required for rilpivirine.

Coadministration has not been studied. 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). No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism. However, rilpivirine is metabolized by CYP3A4 and flucloxacillin could decrease rilpivirine concentrations to a significant extent. Use with caution particularly if flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days).

Coadministration has not been studied. Fluconazole is a moderate inhibitor of CYP3A4. A clinically significant interaction with dolutegravir is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. Coadministration may increase rilpivirine concentrations. No dose adjustment is required for rilpivirine when co-administered with azole antifungal agents, but clinical monitoring for breakthrough fungal infections is recommended when azole antifungals are co-administered with rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with fluconazole. However, given the known QT prolongation risk associated with fluconazole, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase.

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.

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 are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Dolutegravir/rilpivirine does not interact with flunisolide metabolism.

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 CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is therefore little potential for an interaction with dolutegravir and rilpivirine via modulation of, or competition for, metabolic pathways. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with fluorouracil. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Fluorouracil has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. However, rilpivirine should be used with caution when coadministered with a drug that has a potential risk to prolong the QT interval. In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QT interval. Fluphenazine may prolong the QT interval and some European product labels have advised against concurrent use of drugs that prolong the QT interval.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolized by CYP2C9. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

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. 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%. The combination of dolutegravir/rilpivirine and supplements should be used with particular caution. Multivitamins should be co-administered at the same time as dolutegravir/rilpivirine with a meal. If multivitamins cannot be taken at the same time as dolutegravir/rilpivirine, these supplements should be taken well separated in time from the administration of dolutegravir/rilpivirine (minimum 6 hours before or 4 hours after).

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. Dolutegravir and rilpivirine are not expected to inhibit or induce UGT enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. As multiple CYP and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction with dolutegravir and rilpivirine is low. There are no data indicating that formoterol inhibits or induces glucuronidation. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with formoterol. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Formoterol may induce prolongation of the QT interval and the product label for formoterol advises caution in patients treated with drugs affecting the QT interval.

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

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.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by UGT enzymes.

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

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 and rilpivirine do not interfere with this elimination pathway.

Coadministration has not been studied. Garlic supplements have been shown to decrease 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 and rilpivirine could be decreased via induction of CYP3A4 and/or P-gp. Patients should be advised against the use of garlic supplements.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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. Dolutegravir and rilpivirine do not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is mainly glucuronidated by UGT2B7. In vitro data suggest that gemfibrozil inhibits UGT1A1 and UGT1A3. Coadministration could potentially increase dolutegravir concentrations. However, this is unlikely to be clinically significant due to the wide therapeutic window of dolutegravir. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by UGT enzymes.

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.

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 CYP enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gamma-hydroxybutyrate undergoes first pass metabolism. Dolutegravir are rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied. There is no evidence to suggest that ginger inhibits or induces UGTs. Gingerols moderately inhibit CYP3A4 in vitro and could potentially increase the exposure of rilpivirine, but to a limited extent and no dose adjustment is required for rilpivirine. No interaction is expected with dolutegravir.

Coadministration has not been studied. Inconsistent findings for Ginkgo biloba have been reported from clinical drug interaction studies with CYP3A4 substrates, but could reduce exposure of non-boosted protease inhibitors or non-nucleoside reverse transcriptase inhibitors through induction of CYP3A4. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism, but the magnitude and clinical relevance of this potential interaction is difficult to predict for rilpivirine. Use with caution and monitor patients carefully regarding their HIV infection.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interaction with glecaprevir/pibrentasvir. Coadministration of rilpivirine and glecaprevir/pibrentasvir increased rilpivirine Cmax, AUC and Cmin by 105%, 84% and 77%, respectively (n=12); this was deemed within safety limits. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with dolutegravir/rilpivirine.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glimepiride is metabolised by CYP2C9. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is metabolized mainly by CYP2C9, however, dolutegravir or rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

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.

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, however, no significant effect of golden seal root on indinavir pharmacokinetics was observed in a study in HIV-negative subjects. Interactions with other drugs metabolized by CYP3A4 are unlikely. CYP3A4 does not play a major role in dolutegravir metabolism. Although coadministration could potentially increase rilpivirine exposure, this is unlikely to be of clinical significance. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goserelin is mainly hydrolyzed. Dolutegravir and rilpivirine do not interfere with this metabolic pathway. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Granisetron is metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with granisetron. However, the product labels for dolutegravir/rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Granisetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Grapefruit juice inhibits intestinal CYP3A4 and possibly P-gp. Coadministration is unlikely to alter significantly dolutegravir concentrations as CYP3A4 does not play a major role in dolutegravir metabolism. Coadministration may increase rilpivirine concentrations through inhibition of CYP3A4 and possibly P-gp. The magnitude of this potential interaction is difficult to predict as the effect of grapefruit juice is concentration, dose and preparation dependent and varies widely across brands. No a priori dose adjustment is recommended for rilpivirine.

Coadministration has not been studied. Griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels (and therefore reduce the efficacy) of concomitantly administered medicinal products that are metabolized by cytochrome P450 3A4, such as rilpivirine. No interaction is expected with dolutegravir as CYP3A4 does not play a major role in dolutegravir metabolism.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4. Dolutegravir and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with halofantrine. However, given the known QT prolongation risk associated with halofantrine, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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 and rilpivirine are not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with haloperidol. However, given the known QT prolongation risk associated with haloperidol, caution is recommended.

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 and rilpivirine are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. 

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 rilpivirine do not affect these metabolic pathways.

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 or rilpivirine.