Liverpool HIV Interactions

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Abacavir (ABC)

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acamprosate

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acarbose

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acenocoumarol

Quality of Evidence: Very Low

Summary:

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. Cabotegravir was shown to have no inhibitory or inducing effects on CYP1A2, CYP2C9 and CYP2C19 at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acetazolamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion and in vitro studies have shown it may competitively inhibit the renal transporters OAT1, OAT3 and OAT4. Cabotegravir does not cause clinically relevant inhibition of renal transporters and is unlikely to be affected by inhibition of OATs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aciclovir (Acyclovir)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acitretin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as acitretin undergoes isomerisation and glucuronidation. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aclidinium bromide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Adalimumab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Adefovir

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Adrenaline (Epinephrine)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

African Potato

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. 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. Inhibition of CYP3A4 is not problematic because cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Furthermore, inhibition of P-glycoprotein is unlikely to significantly impact cabotegravir intestinal absorption due to its high permeability. Finally, moderate inducers like rifabutin were shown to cause a not clinically significant effect on cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Agomelatine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Albendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Albuvirtide (ABT)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 whereas 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. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alcohol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alcuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcuronium is predominantly excreted unchanged via the kidneys possibly via active tubular secretion. However, cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alendronic Acid (Alendronate)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alfentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes CYP3A4 metabolism, however, cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alfuzosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Alfuzosin is metabolised mainly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized by CYP450 but is a substrate of P-glycoprotein. Cabotegravir does not inhibit or induce CYP enzymes or P-glycoprotein at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Allopurinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Almotriptan

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aloe vera

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Aloe vera is only a weak inhibitor of CYPs in vitro but this is not problematic because cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYPs 2C9, 3A4 and 1A2, with in vivo data suggesting that CYP1A2 plays a more prominent role. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alprazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amantadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Cabotegravir does not inhibit or induce CYP or UGT enzymes, P-glycoprotein, or OATP1B1 at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amikacin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amiloride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged by the kidney with in vitro data indicating that it is a substrate of OCT2. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aminophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Amiodarone inhibits intestinal P-gp but this is unlikely to significantly alter cabotegravir absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amisulpride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally, possibly via OCT. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amodiaquine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amoxicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion via OAT3. Cabotegravir does not cause clinically relevant inhibition of renal transporters

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amphetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Amphetamine is metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amphotericin B

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ampicillin

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of renal transporters

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Anastrozole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Anidulafungin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations contained in antacids resulting in a reduced absorption of cabotegravir. Antacids containing divalent cations should be administered at least 2 hours before or 4 hours after oral cabotegravir.

Description:

Co-administration of antacid supplements has the potential to decrease oral cabotegravir absorption and has not been studied. Antacid products containing polyvalent cations are recommended to be administered at least 2 hours before or 4 hours after oral Vocabria.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Administer antacid products at least 2 hours before or 4 hours after taking Vocabria.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Anti-thymocyte globulin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Apomorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Aprepitant shows a weak inducing effect on UGT on day 8 which is clinically insignificant by two weeks. Any transient change in cabotegravir exposure is unlikely to be clinically significant.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Argatroban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. 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. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Artemisinin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemisinins undergo rapid metabolism via several CYP450 (CYP3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolised via UGTs 1A9 and 2B7. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Ascorbic Acid (Vitamin C) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. A pharmacokinetic interaction is unlikely with vitamin C itself. However, vitamin C can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Asenapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, 2D6 (minor)). Cabotegravir does not inhibit or induce UGT or CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Asparaginase

Quality of Evidence: Very Low

Summary:

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.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aspirin [Acetylsalicylic acid] (Analgesic)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetylsalicylic acid is deacetylated to form salicylic acid which is further glucuronidated. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Aspirin [Acetylsalicylic acid] (Anti-platelet)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolized by CYP2D6, CYP2J2 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atazanavir alone (ATV)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dosage adjustment is necessary.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atazanavir/cobicistat (ATV/c)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant. A comparable effect is expected with atazanavir/cobicistat. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dosage adjustment is necessary.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atazanavir + ritonavir (ATV/r)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant. A comparable effect is expected with atazanavir/ritonavir. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dosage adjustment is necessary.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. Cabotegravir does not cause clinically significant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atovaquone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atropine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely when atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. There is, therefore, little potential for clinically significant interactions with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Avanafil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avanafil is primarily metabolized by CYP3A4 and does not inhibit or induce CYPs or UGTs. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolized analogously to natural purines. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Cabotegravir does not inhibit these transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Baclofen

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Basiliximab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Beclometasone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bedaquiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Belatacept

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Benazepril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bendroflumethiazide

Quality of Evidence: Very Low

Summary:

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%). There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes. Cabotegravir does not inhibit or induce CYPs or UGT enzymes or renal drug transporters at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Benserazide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Benznidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Betahistine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Betamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4 and is a moderate inducer of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Betrixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Cabotegravir does not inhibit or induce P-gp.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bevacizumab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bexarotene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Bexarotene is mainly metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bezafibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as half of bezafibrate dose is eliminated unchanged in the urine.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and bictegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Biperiden

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited human data suggest biperiden undergoes hydroxylation in the liver. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bisacodyl

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Black cohosh (Actaea racemosa, Cimicifuga racemosa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. In vitro studies suggest black cohosh is unlikely to affect UGT1A1 or UGT1A9 at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bleomycin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bortezomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent CYP1A2, 2D6 and 2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Budesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bupivacaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is predominantly metabolized via CYP3A4, however cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Buprenorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine is mainly metabolized by CYP3A4 to form the active metabolite norbuprenorphine. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bupropion (Amfebutamone)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Buspirone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Caffeine citrate

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Calcium folinate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. In theory, calcium could chelate with cabotegravir and potentially decrease the amount of cabotegravir 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 cabotegravir from the IV administration of calcium folinate by 2 hours should eliminate any risk of chelation.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Calcium supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Calcium is eliminated through faeces, urine and sweat. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as calcium resulting in a reduced absorption of cabotegravir. Calcium should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Canagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Candesartan

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cannabidiol (CBD)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit CYP3A4, UGT1A1 or intestinal transporters in the range of doses in clinical use. Cabotegravir does not inhibit or induce CYP or intestinal transporters at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cannabis

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Capecitabine

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Capreomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug, partly by glomerular filtration and possibly partly by tubular secretion (renal transporter not identified). Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Captopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir AUC by 59%. A similar effect is expected with carbamazepine. Therefore, coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance.

Description:

Metabolic inducers may significantly decrease cabotegravir plasma concentration. Concomitant use is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carbidopa

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carbimazole

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carboplatin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Caspofungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. In vitro data indicate that caspofungin is a substrate of the hepatic transporter OATP1B1, however cabotegravir does not inhibit OATP1B1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cat's Claw (Uncaria tomentosa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cefalexin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged via the kidneys (by glomerular filtration and tubular secretion via OAT1 and MATE1). Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cefazolin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cefixime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cefotaxime

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ceftazidime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration,

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ceftriaxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Celecoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is metabolised mainly by CYP2C9, however, cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cetuximab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlorambucil

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolized by glucuronidation via UGT2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlordiazepoxide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chloroquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlorphenamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlortalidone (Chlorthalidone)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ciclesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4 mediated metabolism. Cabotegravir does not interact with ciclesonide metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclosporin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cidofovir

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cilazapril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cimetidine is primarily eliminated by the kidneys. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Ciprofloxacin is primarily eliminated unchanged through the kidneys (by glomerular filtration and tubular secretion via OAT3). Cabotegravir has been shown to inhibit OAT3 in vitro. The interaction between cabotegravir and ciprofloxacin was evaluated using a PBPK model. Coadministration was shown to cause a minimal effect on ciprofloxacin exposure thus, no dosage adjustment is needed.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cisapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cisatracurium

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cisplatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Cisplatin is eliminated renally via OCT2 and MATE1. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clarithromycin is a strong inhibitor of CYP3A4. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clavulanic acid

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clobazam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Clobazam is a weak inducer. However, drug-drug interaction studies with rifabutin (a moderate inducer) have shown no clinically significant decrease in cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clobetasol

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clomifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. CYP2D6 is thought to have a role in clomifene metabolism. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clomipramine (Chlorimipramine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clonazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolized by CYP3A4 and does not induce metabolizing enzymes. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clorazepate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam, which is then metabolized to oxazepam by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cloxacillin

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cocaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Codeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism. Cabotegravir does not inhibit or induce UGT or CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is a substrate of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Colecalciferol (Vitamin D3) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for interaction with cabotegravir via modulation of, or competition for, metabolic pathways. No interaction is expected with vitamin D when given as a single agent (i.e. not with calcium or in a multivitamin preparation) or as an injection. However, vitamin D can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cubeb pepper (Piper cubeba)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, but there is no evidence to suggest that Piper cubeba impacts UGTs.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Cyanocobalamin (Vitamin B12) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with vitamin B12 when given as a single agent (i.e. not in a multivitamin preparation) or as an injection. However, vitamin B12 can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cyclophosphamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cycloserine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cyproterone acetate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cytarabine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The prodrug of dabigatran is a substrate of P-gp. Cabotegravir does not inhibit P-gp at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dacarbazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Dacarbazine is activated to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Daclatasvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is partly metabolized by CYP3A4 and is eliminated for a large part unchanged in the bile. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dactinomycin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dalteparin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dapagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dapsone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapsone is mainly metabolized by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Darifenacin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Darunavir/cobicistat (DRV/c)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Darunavir/cobicistat do not inhibit UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) 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 cabotegravir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Darunavir/cobicistat do not inhibit UGT enzymes and no interactions is expected with emtricitabine and tenofovir alafenamide. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Darunavir + ritonavir (DRV/r)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Induction of UGTs by ritonavir used to boost darunavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dasatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is metabolized by CYP3A4 and inhibits this same enzyme. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Daunorubicin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Delamanid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Denosumab

Quality of Evidence: Very Low

Summary:

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 cabotegravir may be subject to chelation which may result in reduced cabotegravir concentrations.)

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desflurane

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desogestrel (COC)

Quality of Evidence: Very Low

Summary:

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. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter desogestrel exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desogestrel (POP)

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dexmedetomidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGTs 1A4 and 2B10) and cytochrome P450 (mainly 2A6). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dextropropoxyphene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolized by CYP3A, however, cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYPs 3A4 and 2C19) and to temazepam (mainly by CYP3A4). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diclofenac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9 (catalyzes the major route of diclofenac oxidative metabolism). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diethylcarbamazine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Digoxin

Quality of Evidence: Very Low

Summary:

Coadministration 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, which is not inhibited by cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dihydrocodeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dihydroergotamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydroergotamine is a substrate and inhibitor of CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. On the other hand, cabotegravir is metabolized by UGT1A1 and UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diloxanide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diltiazem is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dipyridamole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Disopyramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) whereas 50% of the drug is eliminated unchanged in the urine (possibly via OCT2). Cabotegravir does not cause clinically relevant inhibition of renal transporters and does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Disulfiram

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Docetaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Docetaxel is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dofetilide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Cabotegravir does not cause clinically relevant inhibition of renal transporters

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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%). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dolutegravir (DTG)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Dolutegravir/Lamivudine (DTG/3TC)

Quality of Evidence: Very Low

Summary:

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Dolutegravir/Rilpivirine (DTG/RPV)

Quality of Evidence: Very Low

Summary:

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. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Domperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dopamine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doravirine (DOR)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is not expected to alter concentrations of other antiretroviral products. Doravirine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Delstrigo (doravirine, lamivudine, tenofovir-DF) 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 cabotegravir would be possible from a pharmacokinetic standpoint. Cabotegravir is not expected to alter concentrations of other antiretroviral products. Doravirine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. No interaction is expected with lamivudine and tenofovir-DF.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doxazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doxorubicin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doxycycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No significant metabolism of doxycycline occurs and it is cleared intact by renal and biliary mechanisms.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Droloxifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dronabinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Drospirenone (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter drospirenone exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Drospirenone (HRT)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dulaglutide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Duloxetine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dutasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dydrogesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Echinacea

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Echinacea has a selective effect on CYP3A4 activity (inhibition of intestinal CYP3A4 and induction of hepatic CYP3A4) and its effect on the net exposure of a CYP3A4 substrate will depend on the extraction of the drug at the intestinal and hepatic sites. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ecstasy (MDMA)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Edoxaban

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Efavirenz (EFV)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Efavirenz is a moderate inducer. Based on drug-drug interaction studies with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure is expected not to be clinically relevant. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dose adjustment is required with oral cabotegravir.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eflornithine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as eflornithine is predominantly eliminated unchanged via the kidneys.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Elbasvir/Grazoprevir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elbasvir/grazoprevir are substrate of CYP3A4 and P-glycoprotein. Cabotegravir does not inhibit or induce CYP3A4 and P-glycoprotein.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eltrombopag

Quality of Evidence: Very Low

Summary:

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. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Inhibition of UGT1A1 by eltrombopag is unlikely to significantly alter cabotegravir exposure as coadministration of atazanavir (a strong inhibitor of UGT1A1) was predicted to increase cabotegravir exposure by 11%.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Empagliflozin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Cabotegravir does not inhibit or induce UGTs or P-gp or BCRP at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Emtricitabine (FTC)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Emtricitabine/Tenofovir alafenamide (FTC/TAF)

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

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

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enalapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enflurane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enflurane is predominantly metabolized by CYP2E1, however, cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enoxaparin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Entecavir

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ephedrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ephedrine is predominantly excreted unchanged via renal pathways. There are no available data to determine whether excretion is via active tubular secretion or glomerular filtration. However, cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Epirubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eplerenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Epoprostenol

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eprosartan

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ergometrine (Ergonovine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ergometrine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ergotamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ergotamine is a substrate and inhibitor of CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Erlotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erlotinib is mainly metabolized by CYP3A4, but cabotegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations. Erlotinib is a strong inhibitor of UGT1A1. However, based on the drug interaction study with atazanavir (another strong inhibitor of UGT1A1) this is unlikely to alter cabotegravir exposure to a clinically significant extent.

Description:

No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. erlotinib).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ertapenem

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erythromycin is a moderate inhibitor of CYP3A4 but No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Eslicarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is an inducer of UGT and is expected to decrease the exposure of cabotegravir. Coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Estazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Estradiol

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Estramustine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ethambutol

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ethinylestradiol

Quality of Evidence: Low

Summary:

Coadministration of cabotegravir (30 mg once daily) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly affect ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau; levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively. No dose adjustment of oral contraceptives is necessary when coadministered with cabotegravir. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Description:

Coadministration of ethinyl estradiol, levonorgestrel and oral cabotegravir increased ethinyl estradiol AUC by 2%, decreased Cmax by 8% and had no effect on Ctau. Levonorgestrel AUC, Cmax and Ctau increased by 12%, 5% and 7%, respectively. Cabotegravir did not significantly change ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. No dose adjustment of oral contraceptives is necessary when coadministered with Vocabria tablets.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, oral contraceptives containing levonorgestrel and ethinyl estradiol can be coadministered with cabotegravir without a dose adjustment. Coadministration of ethinylestradiol (0.03 mg once daily) and cabotegravir (30 mg once daily) was studied in 19 subjects. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau. Coadministration of levonorgestrel (0.15 mg once daily) and cabotegravir (30 mg once daily) was studied in 19 subjects. Levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and an oral contraceptive containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) was studied in 19 female subjects. Ethinylestradiol AUC increased by 2% and Cmax decreased by 7%; levonorgestrel AUC and Cmax increased by 12% and 5%. Steady-state cabotegravir pharmacokinetic parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations. These results support cabotegravir coadministration with ethinylestradiol/levonorgestrel oral contraceptives in clinical practice.

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women. Trezza C, Ford SL, Gould E, et al. Br J Clin Pharmacol. 2017 Jul;83(7):1499-1505.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ethionamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver with animal studies suggesting involvement of flavin-containing monooxygenases.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ethosuximide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethosuximide is mainly metabolized by CYP3A4 and does not induce metabolizing enzymes. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etidocaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etidocaine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etonogestrel (implant)

Quality of Evidence: Very Low

Summary:

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etonogestrel (vaginal ring)

Quality of Evidence: Very Low

Summary:

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter etonogestrel exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etoposide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Etoposide is partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. Furthermore, etoposide is partly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etravirine (ETR)

Quality of Evidence: Low

Summary:

Coadministration of etravirine (200 mg twice daily) and oral cabotegravir (30 mg once daily) did not significantly alter cabotegravir concentrations. Cabotegravir AUC and Cmax increased by 4% and 1%, and there was no change in Ctau. (n=12). Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dose adjustment is required.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. Coadministration of etravirine and oral cabotegravir increased cabotegravir AUC and Cmax by 1% and 4% and had no effect on Ctau. Etravirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria tablets is necessary.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, etravirine can be coadministered with cabotegravir without a dose adjustment. Coadministration of etravirine (200 mg twice daily) and cabotegravir (30 mg once daily) was studied in 12 subjects. Cabotegravir AUC and Cmax increased by 4% and 1%, and there was no change in Ctau.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and etravirine (200 mg twice daily) was studied in 12 subjects. Cabotegravir and etravirine in combination for 14 days were well tolerated and there was no significant effect of etravirine on cabotegravir pharmacokinetics (AUC and Cmax increased by 1% and 4%; no change in C24). Etravirine pharmacokinetics parameters were in the range of historical values reported for etravirine alone in healthy subjects. These results indicate that no dose adjustment of cabotegravir is required when coadministered with etravirine.

Ford SL, Gould E, Chen S, et al. Effects of etravirine on the pharmacokinetics of the integrase inhibitor S/GSK1265744. Antimicrob Agents Chemother. 2013;57(1):277-80.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eucalyptus globulus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eucalyptus is only a weak inhibitor of CYP3A4 and there is no evidence to suggest that eucalyptus impacts UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Everolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Everolimus is metabolized by CYP3A4 and is a modest inhibitor of CYP3A4 in vivo. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Evolocumab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Exemestane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exemestane is metabolized by CYP3A4 and aldoketoreductase. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Exenatide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ezetimibe

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Famciclovir

Quality of Evidence: Very Low

Summary:

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. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famotidine is eliminated by renal excretion via OAT3 (65-70%) and by metabolic routes (30-35%). Cabotegravir does not inhibit renal transporters to a clinically significant extent. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Felodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fenofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolyzed to an active metabolite, fenofibric acid.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fentanyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism, however, cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fesoterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine does not undergo CYP-mediated metabolism but is a substrate of P-glycoprotein. Cabotegravir does not inhibit or induce P-gp at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Finasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fish oils

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion of the parent drug also eliminated unchanged renally. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flibanserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flibanserin is primarily metabolized by CYP3A4 and has been shown to moderately increase the exposure of simvastatin, a CYP3A4 substrate. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9 but does not cause clinically relevant inhibition of OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 and also has inducing effects on UGTs, however, no significant effect is expected on cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is a moderate inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flucytosine

Quality of Evidence: Very Low

Summary:

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.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fludarabine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fludrocortisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flunisolide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide is metabolised by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flunitrazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYPs 3A4 and 2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluocinolone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluorouracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 cabotegravir via modulation of, or competition for, metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flurazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluticasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluvastatin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Folic acid [alone]

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Folic acid [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. Cabotegravir does not interfere with this metabolic pathway. A pharmacokinetic interaction is unlikely with folic acid itself. However, folic acid can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fondaparinux

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Formestane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. Cabotegravir does not interfere with formestane’s metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Formoterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Foscarnet

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fosinopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). Cabotegravir does not inhibit or induce UGT enzymes or renal drug transporters at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gabapentin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ganciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Garlic

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although garlic has been shown to induce intestinal P-gp, this is unlikely to affect cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gefitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Gefitinib is metabolized by CYP3A4 and 2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gemcitabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Gemcitabine is metabolized in the liver by cytidine deaminase to an inactive metabolite. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gemfibrozil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is mainly glucuronidated by UGT2B7 and in vitro data suggest that it inhibits UGT1A1 and UGT1A3. Gemfibrozil is unlikely to alter cabotegravir exposure to a clinically significant extent. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and the coadministration of atazanavir (a strong UGT1A1 inhibitor) was predicted to increase cabotegravir exposure by 11% only.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gentamicin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gestodene (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter gestodene exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

GHB (Gamma-hydroxybutyrate)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ginger (Zingiber officinale)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Gingerols moderately inhibit CYP3A4 in vitro but there is no evidence to suggest that they inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ginkgo biloba

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ginkgo biloba induces CYP3A4 but is unlikely to alter cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glecaprevir/Pibrentasvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glecaprevir and pibrentasvir inhibit P-glycoprotein. Cabotegravir is a substrate of P-glycoprotein but inhibition of this transporter is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glibenclamide (Glyburide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gliclazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glimepiride

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glipizide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is metabolized mainly by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glyceryl trinitrate (Nitroglycerin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glycopyrronium bromide (Glycopyrrolate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Cabotegravir does not cause clinically significant inhibition of renal transporters and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Goldenseal root (Hydrastis canadensis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goldenseal has been shown to inhibit CYP3A4 in vitro but is unlikely to alter cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Goserelin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Granisetron is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inhibition of intestinal CYP3A4 by grapefruit juice is not expected to affect cabotegravir as it undergoes metabolism mainly via UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Griseofulvin undergoes glucuronidation and has inducing properties. Given the limited drug-drug interaction data, it is unclear whether griseofulvin can cause a clinically significant decrease in cabotegravir exposure. Therefore coadministration should be avoided.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Halofantrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Cabotegravir does not inhibit or induce UGT or CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Halothane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that halothane undergoes oxidation (mainly via CYP2E1 and to a lesser extent CYP2A6) and reduction (via CYP2A6 and CYP3A4). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Heparin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Heroin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant pharmacokinetic interaction is unlikely. When used illicitly, heroin is mainly injected or inhaled through the nose and goes directly in the bloodstream. Heroin is then rapidly deacetylated to 6-monoacetylmorhine (6-MAM) and subsequently to morphine by plasma and liver esterase, respectively. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hops (Humulus lupulus)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that 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%). No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

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

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

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

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

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as hydralazine is metabolised via primary oxidative metabolism and acetylation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydrochlorothiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Cabotegravir does not inhibit or induce CYP3A4 or CYP2D6 at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydrocortisone (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydrocortisone (topical)

Quality of Evidence: Very Low

Summary:

No clinically significant interactions are expected with the topical use of hydrocortisone.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydroxycarbamide (Hydroxyurea)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyurea undergoes metabolism via non-CYP mediated metabolism and is unlikely to affect concentrations of cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydroxyzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ibalizumab-uiyk (IBA)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Cabotegravir is not expected to alter concentrations of other antiretroviral products. Dose modifications of ibalizumab are not required when administered with any other antiretroviral.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ibandronic acid (Ibandronate)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ibuprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ifosfamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Iloprost

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloprost is extensively metabolized via beta oxidation of the carboxyl side chain with only a minor role for CYP metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Imatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Imatinib is primarily metabolized by CYP3A4 and to a lesser extent CYP1A2, 2D6, 2C9, 2C19. In vitro data indicate that imatinib inhibits CYP3A4, 2D6, 2C9, 2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Imipenem/Cilastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and, to a lesser extent, by active tubular secretion. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Indacaterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indacaterol is eliminated partly unchanged (33%) and partly metabolized by CYP3A4 and UGT1A1. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolized by CYP450, however, cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nonpegylated interferon alpha appears to be metabolized principally in the kidney.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Inula racemosa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Alantolactone, a component of Inula racemosa, moderately inhibits CYP3A4 in vitro, but there is no evidence that Inula racemosa affects UGTs or P-gp.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Iodine [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Iodine is converted to iodide, which is trapped in the thyroid gland. Iodides are excreted mainly in the urine with smaller amounts excreted in the faeces, sweat and saliva. A pharmacokinetic interaction is unlikely with iodine itself. However, iodine can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ipratropium bromide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Irbesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Irbesartan is metabolized by glucuronidation and oxidation (mainly CYP2C9). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Irinotecan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Irinotecan is converted to its active metabolite SN38 via tissue carboxylesterase and to inactive metabolites (APC, NPC) via CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Iron supplements (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as iron resulting in a reduced absorption of cabotegravir. Iron supplements should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isoflurane

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isoniazid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Cabotegravir is unlikely to interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isosorbide dinitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Isosorbide dinitrate undergoes extensive first past metabolism, predominantly in the liver, with less than 30% of a dose undergoing subsequent glucuronidation. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isotretinoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isotretinoin is metabolised mainly by CYP2C8 and CYP3A4 with the participation of CYP2B6 and CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Itraconazole is a strong inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivabradine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolised by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivermectin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest ivermectin is predominantly metabolised by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Kanamycin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ketamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketamine is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 2B6 and 2C9 in the range of concentrations used in anaesthesia. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. In addition, cabotegravir does not inhibit or induce other CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketoconazole is a strong inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Labetalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated by UGTs 1A1 and 2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lacidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lacosamide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lactulose

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lamivudine (3TC)

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lamotrigine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lamotrigine is mainly glucuronidated by UGT1A4. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lapatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Lapatinib is metabolized by CYP3A4 and inhibits this same enzyme. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ledipasvir/Sofosbuvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ledipasvir and sofosbuvir are weak inhibitors of intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lenalidomide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lercanidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Letrozole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Letrozole is metabolised by CYP3A4 and CYP2A6 to carbinol, an inactive metabolite. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Leuprorelin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levamisole (Ergamisol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism and elimination of levamisole has not been well characterized. Based on limited information, and single dose use of levamisole, clinically significant interactions are not considered likely.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levetiracetam

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levocetirizine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levodopa

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (COC)

Quality of Evidence: Low

Summary:

Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly affect ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau; levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively. No dose adjustment of oral contraceptives is necessary when coadministered with cabotegravir.

Description:

Coadministration of ethinyl estradiol, levonorgestrel and oral cabotegravir increased ethinyl estradiol AUC by 2%, decreased Cmax by 8% and had no effect on Ctau. Levonorgestrel AUC, Cmax and Ctau increased by 12%, 5% and 7%, respectively. Cabotegravir did not significantly change ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. No dose adjustment of oral contraceptives is necessary when coadministered with Vocabria tablets.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, oral contraceptives containing levonorgestrel and ethinyl estradiol can be coadministered with cabotegravir without a dose adjustment. Coadministration of ethinylestradiol (0.03 mg once daily) and cabotegravir (30 mg once daily) was studied in 19 subjects. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau. Coadministration of levonorgestrel (0.15 mg once daily) and cabotegravir (30 mg once daily) was studied in 19 subjects. Levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and an oral contraceptive containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) was studied in 19 female subjects. Ethinylestradiol AUC increased by 2% and Cmax decreased by 7%; levonorgestrel AUC and Cmax increased by 12% and 5%. Steady-state cabotegravir pharmacokinetic parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations. These results support cabotegravir coadministration with ethinylestradiol/levonorgestrel oral contraceptives in clinical practice.

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women. Trezza C, Ford SL, Gould E, et al. Br J Clin Pharmacol. 2017 Jul;83(7):1499-1505.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Cabotegravir is unlikely to alter levonorgestrel used as emergency contraception.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (HRT)

Quality of Evidence: Very Low

Summary:

Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Cabotegravir is unlikely to alter levonorgestrel used as hormone therapy replacement. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (implant)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Cabotegravir is unlikely to alter levonorgestrel used as implant.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (IUD)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levonorgestrel (POP)

Quality of Evidence: Very Low

Summary:

Coadministration with a levonorgestrel progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Levothyroxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linagliptin is mainly eliminated as parent compound in faeces, with metabolism by CYP3A4 representing a minor elimination pathway. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Linezolid

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Liquorice (Glycyrrhiza glabra)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycyrrhizin, the main active component of Glycyrrhiza glabra, is a modest inducer of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Liraglutide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lisinopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lithium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys and is freely filtered at a rate that is dependent upon the glomerular filtration rate.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is metabolized by CYP2C8 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lopinavir/ritonavir (LPV/r)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir used to boost lopinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Loratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lorazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorazepam is mainly glucuronidated (by UGTs 2B15, 2B4, 2B7, 1A7, 1A10). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lormetazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated (possibly by UGTs 2B15, 1A9 and 2B7). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Losartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lovastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

LSD (Lysergic acid diethylamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. LSD (lysergic acid diethylamide) is metabolized to O-H-LSD and N-desmethyl-LSD partly by CYP (unknown isoenzyme). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lumefantrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lumefantrine is metabolized predominantly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Macitentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolized mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Magnesium supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as magnesium resulting in a reduced absorption of cabotegravir. Magnesium supplements should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Malabar nut tree (Justicia adhatoda, Adhatoda vasica)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data are available on the effect of malabar nut tree on drug metabolism. In vitro data with leaf extracts suggest it could act as an inducer of phase I and phase II metabolic enzymes although the clinical relevance has not been evaluated. However, no clinically significant effect is expected on oral cabotegravir based on the drug interaction study with rifabutin (a moderate inducer).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mannitol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Mannitol is metabolised only very slightly, if at all, to glycogen in the liver and is predominantly eliminated unchanged via glomerular filtration. There is little potential for mannitol to affect the disposition of antiretrovirals, or to be altered by antiretrovirals.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Maprotiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Maraviroc (MVC)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maraviroc is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mebendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significantinteraction is unlikely. Mebendazole is predominantly metabolized in the liver. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Medroxyprogesterone (depot injection)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Medroxyprogesterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Medroxyprogesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with medroxyprogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mefenamic acid

Quality of Evidence: Very Low

Summary:

Cabotegravir is metabolized by UGT1A1 and to a lesser extent by UGT1A9. The interaction with mefenamic acid, a strong UGT1A9 inhibitor, was assessed using a PBPK model. Coadministration is predicted to increase cabotegravir exposure by 11%, which is considered to be not clinically relevant.

Description:

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mefloquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefloquine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Megestrol acetate

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Meglumine antimoniate

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Melarsoprol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely, although due to the lack of available data, vigilance is required if administering melarsoprol with antiretrovirals. It is unknown whether urinary metabolites of melarsoprol, such as arsenic, are excreted via active renal mechanisms. However a clinical study has reported that urinary pharmacokinetic parameters are not predictive of toxicity or therapeutic efficacy.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Menthol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Menthol is a moderate inhibitor of CYP3A4 but there is no evidence to suggest that menthol affects UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mephedrone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Mephedrone is metabolized mainly by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mercaptopurine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mercaptopurine is predominantly metabolised by xanthine oxidase and cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Meropenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporters OAT3/OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1/OAT3.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mesalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolized to N-acetyl-mesalazine by N-acetyltransferase and cabotegravir does not interfere with this pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mesna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesna is rapidly oxidised to its only metabolite, mesna disulphide via the physiological cysteine system. Approximately 32% and 33% of an administered dose is eliminated in the urine in 24 hours as mesna and mesna disulphide respectively.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metformin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metformin is eliminated renally via OCT2 and MATE1. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methadone is metabolized by CYP2B6 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methamphetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Methamphetamine is mainly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CY enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Methotrexate (Amethopterin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been assessed in clinical studies. Cabotegravir inhibits in vitro the renal transporters OAT1 and OAT3. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion via OAT1, OAT3. Although PBPK modelling suggests that OAT1/OAT3 inhibition is not clinically relevant (<25% mean increase in exposure of OAT1 or OAT3 substrates with oral cabotegravir), the European product label for cabotegravir recommends caution when coadministering with a narrow therapeutic index drug such as methotrexate. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Description:

Caution is advised when co-dosing with narrow therapeutic index OAT1/3 substrate drugs (e.g. methotrexate).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methyldopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged, and as the mono-O-sulfate conjugate.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methylphenidate

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methylprednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metoclopramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metolazone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metronidazole

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mexiletine is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolized by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Miconazole inhibits CYP2C9 and CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Midazolam (oral)

Quality of Evidence: Very Low

Summary:

Coadministration of cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) did not alter midazolam pharmacokinetics to a clinically significant extent. Midazolam Cmax and AUC increased by 9% and 10% (n=12).

Description:

In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, midazolam can be coadministered with cabotegravir without a dose adjustment. Coadministration of midazolam (3 mg) and cabotegravir (30 mg once daily) was studied in 12 subjects. Midazolam Cmax and AUC increased by 9% and 10%.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) was studied in 12 subjects and was found not to significantly affect midazolam pharmacokinetics (AUC and Cmax increased by 8% and 9%).

Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Reese MJ, Bowers GD, Humphreys JE, et al. Xenobiotica. 2016;46(5):445-56.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Coadministration with parenteral midazolam has not been studied. Coadministration of cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) did not alter midazolam pharmacokinetics to a clinically significant extent (Cmax and AUC increased by 9% and 10%, n=12). A similar effect is expected with parenteral midazolam.

Description:

In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, midazolam can be coadministered with cabotegravir without a dose adjustment. Coadministration of midazolam (3 mg) and cabotegravir (30 mg once daily) was studied in 12 subjects. Midazolam Cmax and AUC increased by 9% and 10%.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) was studied in 12 subjects and was found not to significantly affect midazolam pharmacokinetics (AUC and Cmax increased by 8% and 9%).

Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Reese MJ, Bowers GD, Humphreys JE, et al. Xenobiotica. 2016;46(5):445-56.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mifepristone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest that mifepristone may inhibit CYP3A4 metabolism. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Milk thistle (Silybum marianum, silymarin)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Milnacipran

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Miltefosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Based on limited data concerning metabolism, elimination and toxicity of miltefosine, there is little potential for interaction. In vitro studies have shown that interactions between miltefosine and drugs which are metabolised by cytochrome P450, glucuronidated or otherwise conjugated are unlikely. The main metabolic pathway of miltefosine appears to be mediated by phospholipases.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Minaxolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minaxolone undergoes hepatic metabolism. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mirabegron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirabegron is metabolized by multiple pathways including hydrolysis, glucuronidation and oxidation by CYP2D6 and CYP3A4. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Misoprostol

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mitoxantrone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Mitoxantrone is metabolized to inactive carboxylic acid derivatives possibly by CYP450. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Modafinil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Modafinil is largely metabolized by hydrolysis (esterase-mediated) and to a lesser extent by CYP3A4-mediated oxidative metabolism. Cabotegravir has no inhibitory effect on CYP3A4. Modafinil is unlikely to impact cabotegravir as it is metabolized mainly by UGT1A1 and to a lesser extent by UGT1A9 and there is no evidence that modafinil induces UGT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolized by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Moxifloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Multivitamins

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Multivitamins may contain polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as magnesium resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGTs 1A9 and 2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Naftidrofuryl

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Naloxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naloxone is mainly glucuronidated by UGT2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Naltrexone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nandrolone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Naproxen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nateglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is mainly metabolized by CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nebivolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nefazodone is metabolized mainly by CYP3A4 and is also an inhibitor of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Neostigmine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nevirapine (NVP)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nevirapine is a weak inducer. Based on drug-drug interaction studies with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure is expected not to be clinically relevant. No dose adjustment is required with oral cabotegravir. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicardipine is metabolised mainly by CYP3A4 and inhibits this same enzyme. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Niclosamide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nicorandil

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Nicotinamide (Niacinamide) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolized by xanthine oxidase and aldehyde oxidase. A pharmacokinetic interaction is unlikely with nicotinamide itself. However, nicotinamide can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nifedipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nifurtimox

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifurtimox appears to be biotransformed mostly by NADPH P450 reductase.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nilotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Nilotinib is metabolized by CYP3A4 and inhibits this same enzyme. Furthermore, in vitro data indicate that nilotinib inhibits UGT1A1. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, but it is unlikely to be affected by nilotinib as coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase oral cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nimesulide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nimesulide is extensively metabolized in the liver following multiple pathways including CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nisoldipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised mainly by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nitrendipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolized mainly by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nitrofurantoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolized in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug. Cabotegravir does not interfere with nitrofurantoin elimination.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nitrous oxide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norelgestromin (patch)

Quality of Evidence: Very Low

Summary:

Coadministration with transdermally delivered norelgestromin/ethinylestradiol has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolized to norgestrel (possibly by CYP3A4). Ethinylestradiol is mainly metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter norelgestromin exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norethisterone [Norethindrone] (COC)

Quality of Evidence: Very Low

Summary:

Coadministration of a combined oral contraceptive (COC) containing norethisterone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter norethisterone exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norethisterone [Norethindrone] (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with norethisterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norethisterone [Norethindrone] (IM depot injection)

Quality of Evidence: Very Low

Summary:

Coadministration of a norethisterone IM depot injection has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norethisterone [Norethindrone] (POP)

Quality of Evidence: Very Low

Summary:

Coadministration of a norethisterone progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norgestimate (COC)

Quality of Evidence: Very Low

Summary:

Coadministration of a combined oral contraceptive (COC) containing norgestimate has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is deacetylated to the active metabolite norelgestromin which is then metabolised to norgestrel, possibly by CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter norgestimate exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norgestrel (COC)

Quality of Evidence: Very Low

Summary:

Coadministration of a combined oral contraceptive (COC) containing norgestrel/ethinylestradiol has not been studied. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, cabotegravir is unlikely to alter norgestrel exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norgestrel (HRT)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolized mainly by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nystatin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged in the kidneys by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Olanzapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolized mainly by CYP1A2, but also by glucuronidation (UGT1A4). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Olmesartan

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Olodaterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olodaterol is metabolized by CYP2C8, CYP2C9, is glucuronidated via several UGTs, and is a substrate of P-gp. Cabotegravir does not inhibit or induce CYP or UGT enzymes, or P-glycoprotein at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ombitasvir/Paritaprevir/r

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No interaction is expected with ombitasvir. Paritaprevir/ritonavir inhibit intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ombitasvir/Paritaprevir/r + Dasabuvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No interaction is expected with ombitasvir or dasabuvir. Paritaprevir/ritonavir and dasabuvir inhibit intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omeprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Orlistat

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oseltamivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oseltamivir is converted to oseltamivir carboxylate by esterases. The latter is excreted in the urine by glomerular filtration and tubular secretion by OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxaliplatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Oxaliplatin undergoes non-enzymatic biotransformation and is eliminated renally via OCT2 and MATE2-K. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxamniquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Oxamniquine is thought to be predominantly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxandrolone

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated (by UGTs 2B15, 1A9 and 2B7). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Cabotegravir exposure is expected to decrease due to induction of UGT by oxcarbazepine and thereby result in loss of therapeutic effect and development of resistance.

Description:

Metabolic inducers may significantly decrease cabotegravir plasma concentration. Concomitant use is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxprenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised by glucuronidation. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxybutynin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxybutynin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Oxycodone is metabolised principally by CYP3A and CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxytocin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elimination of oxytocin occurs via the liver, kidney, functional mammary gland and oxytocinase. The plasma half-life is approximately five minutes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Paclitaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. In vitro data suggest that paclitaxel activates PXR and therefore has potential inducing properties. No significant effect is expected on oral cabotegravir based on the drug interaction study with rifabutin (a moderate inducer).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly OCT), with minimal metabolism occurring via CYP2D6 and 3A4. Cabotegravir does not cause clinically relevant inhibition of renal transporters and was shown to have no inhibitory or inducing effects on CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Para-aminosalicylic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Paromomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as paromomycin is not metabolized, but is eliminated unchanged by renal glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Paroxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYPs 2D6 and 3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pazopanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Pazopanib is metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C8. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. In vitro data indicate that pazopanib inhibits UGT1A1. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, but it is unlikely to be affected by pazopanib as coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase oral cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is primarily metabolised by UGT1A1, and to a lesser extent by UGT1A9. These pathways are not affected by peginterferon alfa-2a. The metabolism of peginterferon alfa-2a is not fully characterized, however, studies in rats indicate that the kidney is a major organ for excretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Peginterferon alfa-2b

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is primarily metabolised by UGT1A1, and to a lesser extent UGT1A9. These pathways are not affected by peginterferon alfa-2b.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Penicillamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although metabolism of penicillamine is not fully elucidated, multiple mechanisms and sites of metabolism are thought to be involved. There is, therefore, low potential for clinically significant interactions with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Penicillins

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Cabotegravir does not cause clinically relevant inhibition of OAT1/OAT3.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pentamidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The exact metabolic pathway of pentamidine has not been clearly established. Data from animal studies suggest the involvement of CYPs 1A1, 2D6 and 2C19 in the oxidative metabolism of pentamidine. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pentoxifylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pentoxifylline has not been well described but some studies indicate oxidation by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is demethylated by CYP3A4 and to a lesser extent by CYP2C9, and oxidated by FMO3. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Periciazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Perindopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolized to other inactive metabolites. Elimination occurs predominantly via the urine.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pethidine (Meperidine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolized mainly by CYP2B6 and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Phencyclidine (PCP)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Phencyclidine is extensively metabolized to inactive metabolites by a variety of metabolic routes (mainly CYP3A4). Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Phenelzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolized by oxidation via monoamine oxidase and to a lesser extent by acetylation.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. The interaction between phenobarbital (an inducer of UGT1A1) and oral cabotegravir (30 mg once daily) was evaluated using a PBPK model, which predicted a 28% decrease in cabotegravir exposure. Coadministration is contraindicated due to potential for loss of therapeutic effect and development of resistance.

Description:

Metabolic inducers may significantly decrease cabotegravir plasma concentration. Concomitant use is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of phenobarbital (an inducer of UGT1A1) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 28% decrease in oral cabotegravir exposure, comparable to observed rifabutin data.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenprocoumon is metabolized by CYP2C9 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir AUC by 59%. A similar effect is expected with phenytoin. Therefore coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance.

Description:

Metabolic inducers may significantly decrease cabotegravir plasma concentration. Concomitant use is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Potential Interaction

Cabotegravir [oral] (CAB oral)

Phytomenadione (Vitamin K) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Metabolism of phytomenadione is thought to involve CYP4F2 and glucuronidation. Renal elimination of phytomenadione is minimal. A pharmacokinetic interaction is unlikely with phytomenadione itself. However, phytomenadione can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pilocarpine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely when pilocarpine is used either orally or as eye drops. Pilocarpine is primarily metabolized by CYP2A6 and serum esterases. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is metabolized mainly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pindolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolized to hydroxymetabolites (possibly by CYP2D6) and partly eliminated unchanged in the urine.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolized by mainly CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Piperacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piperacillin is eliminated renally via glomerular filtration and active secretion by OAT1/3. Cabotegravir does not cause clinically relevant inhibition of OAT1/OAT3.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Piperaquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piperaquine is a modest inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Piroxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolized by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Poppers (Amyl nitrate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Amyl nitrate is metabolized rapidly by hydrolytic denitration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Posaconazole is eliminated mainly unchanged in the faeces and only a minimal amount undergoes biotransformation (mainly glucuronidation by UGT1A4). Posaconazole is a strong inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely as potassium is eliminated renally.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pramipexole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pramipexole is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OCT2. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prasugrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pravastatin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Praziquantel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Praziquantel is predominantly metabolised via CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin undergoes extensive hepatic metabolism primarily by demethylation and conjugation. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone is metabolised by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prednisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pregabalin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Primaquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Primaquine is metabolised mainly through a non-CYP mediated mechanism and only a small fraction of the drug is believed to be metabolised through CYP450. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Primidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Primidone is metabolised by CYP3A4 to the active metabolite phenobarbital. The interaction between phenobarbital (inducer of UGT1A1) and oral cabotegravir (30 mg once daily) was evaluated using a PBPK model, which predicted a 28% decrease in cabotegravir exposure. The US product information contraindicates the coadministration due to potential for loss of therapeutic effect and development of resistance.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Probenecid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. In vitro data suggest that probenecid is a non-selective inhibitor of UGT however it is unlikely to significantly impact cabotegravir exposure. Coadministration with the strong UGT1A1 inhibitor atazanavir was indeed predicted to minimally increase cabotegravir exposure (11%).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Procarbazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Procarbazine is metabolized to azoprocarbazine by CYP450 (mainly CYP2B and CYP1A) and monoamine oxidase. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Proguanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Proguanil is partly excreted unchanged and partly metabolized to its more active metabolite cycloguanil by CYP2C19 and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolized mainly by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2 and CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Propofol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propofol is glucuronidated via UGT1A9 and UGT1A8, and is oxidized mainly via CYP2B6. Cabotegravir was shown to have no inhibitory or inducing effects on CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolized by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Propylthiouracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. Propylthiouracil is extensively metabolised, predominantly via glucuronidation, but the exact glucuronidation pathways are unknown. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Protamine sulphate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. The metabolism of protamine has not been fully elucidated, however protamine complexed with heparin is thought to be partially metabolised by fibrinolysin.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pyrantel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrantel is metabolized by CYP2D6 in vitro, however, absorption of an oral dose is minimal and over 50% of a dose is excreted unchanged in the faeces.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pyrazinamide

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pyridostigmine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. Pyridostigmine is mainly eliminated unchanged by the kidney (via glomerular filtration and active tubular secretion most likely by a cation transporter). Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Pyridoxine (Vitamin B6) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Pyridoxine is absorbed from the GI tract and is converted to the active form pyridoxal phosphate. It is excreted in the urine as 4-pyridoxic acid. A pharmacokinetic interaction is unlikely with pyridoxine itself. However, pyridoxine can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pyrimethamine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Quercetin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Quercetin has the ability to modulate CYP/P-gp activities although there are inconsistencies in the literature. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Quetiapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is metabolized mainly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Quinapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, based on metabolism and clearance a clinically significant interaction is unlikely. Quinapril is de-esterified to the active metabolite quinaprilat, which is eliminated primarily by renal excretion via OAT3. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinidine is metabolized by CYP3A4, however, cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Quinine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinine is extensively metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Raltegravir (RAL)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is mainly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ramipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranitidine is excreted via the kidney, partially by the cationic system. Cabotegravir does not cause clinically relevant inhibition of renal transporters. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranolazine is primarily metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rasagiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as rasagiline is metabolised predominantly by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Reboxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Red yeast rice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Red yeast rice contains monacolin K, a natural component with the same chemical structure as lovastatin. Monacolin K is metabolised by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Repaglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolized by CYPs 2C8 and 3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Retinol (Vitamin A) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. A pharmacokinetic interaction is unlikely with retinol itself. However, retinol can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ribavirin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ribavirin is partly metabolized (non CYP mediated) and partly excreted in the urine. Cabotegravir does not cause clinically significant inhibition of renal transporters.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Riboflavin (Vitamin B2) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. A pharmacokinetic interaction is unlikely with riboflavin itself. However, riboflavin can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration of rifabutin (300 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir Cmax by 17%, AUC by 23% and Ctrough by 26%. This reduction in cabotegravir exposure is not considered to be clinically relevant. No dose adjustment is needed with oral cabotegravir.

Description:

Coadministration of rifabutin and oral cabotegravir decreased cabotegravir AUC, Cmax and Ctau by 21%, 17% and 8%. Rifabutin did not significantly change cabotegravir plasma concentration. No dose adjustment is required. Prior to initiation of oral cabotegravir therapy, the prescribing information for Vocabria injection should be consulted regarding concomitant use with rifabutin.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, rifabutin can be coadministered with cabotegravir without a dose adjustment. Rifabutin can be coadministered with cabotegravir; however, it is contraindicated with Cabenuva (cabotegravir; rilpivirine) extended-release injectable suspensions. Coadministration of rifabutin (300 mg once daily) and cabotegravir (30 mg once daily) was studied in 12 subjects. Cabotegravir Cmax, AUC and Ctau decreased by 17%, 23% and 26%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and rifabutin (300 mg once daily) was studied in 12 subjects and was found to decrease cabotegravir AUC, Cmax and C24 by 21%, 17% and 26%, respectively. Rifabutin had a modest impact on plasma cabotegravir exposure and overall plasma cabotegravir trough exposures remained above the 10 mg oral dose shown to maintain viral suppression in HIV-1-infected subjects. Oral cabotegravir can be coadministered with rifabutin without dosage adjustment.

Effect of rifabutin on the pharmacokinetics of oral cabotegravir in healthy subjects. Ford SL, Lou Y, Lewis N, et al. Antivir Ther. 2019;24(4):301-308.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Rifampicin

Quality of Evidence: Low

Summary:

Concomitant administration with rifampicin is contraindicated due to the potential for loss of therapeutic effect and development of resistance. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir Cmax, AUC and C24 by 6%, 59% and 50%, respectively.

Description:

Coadministration of rifampicin and oral cabotegravir decreased cabotegravir AUC and Cmax by 59% and 6%. Rifampicin significantly decreased cabotegravir plasma concentration which is likely to result in loss of therapeutic effect. Dosing recommendations for co-administration of Vocabria with rifampicin have not been established and co-administration of Vocabria with rifampicin is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance. Coadministration of rifampin (600 mg once daily) and cabotegravir (30 mg single dose) was studied in 15 subjects. Cabotegravir Cmax, AUC and Ctau decreased by 6%, 59% and 50%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and rifampicin (600 mg once daily) was studied in 15 subjects and was found to decrease cabotegravir AUC, Cmax and C24 by 21%, 17% and 26%, respectively. Rifampicin decreased cabotegravir AUC and Cmax by 59% and 6%. Half-life decreased by 57% and oral clearance was increased by 2.4-fold. Concomitant administration of rifampicin with oral and long-acting formulations of cabotegravir is not recommended currently without further study.

Effect of rifampin on the single-dose pharmacokinetics of oral cabotegravir in healthy subjects. Ford SL, Sutton K, Lou Y, et al. Antimicrob Agents Chemother. 2017;61(10):e00487-17.

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir Cmax by 6%, AUC by 59% and oral clearance was increased by 2.4 fold. A similar effect is expected with rifapentine. Thus concomitant administration is contraindicated due to the potential for loss of therapeutic effect and development of resistance.

Description:

Rifapentine may significantly decrease cabotegravir plasma concentrations. Concomitant use is contraindicated.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rifaximin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rilpivirine (RPV)

Quality of Evidence: Low

Summary:

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) did not significantly alter cabotegravir and rilpivirine pharmacokinetics (n=11). Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively; rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. No dose adjustment is required.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. Coadministration of rilpivirine and oral cabotegravir increased cabotegravir AUC, Cmax and Ctau by 12%, 5% and 14%, respectively; rilpivirine AUC, Cmax Ctau decreased by 1%, 4% and 8%. Rilpivirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria tablets is necessary when co-administered with rilpivirine.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, rilpivirine can be coadministered with cabotegravir without a dose adjustment. Coadministration of rilpivirine (25 mg once daily) and cabotegravir (30 mg once daily) was studied in 11 subjects. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively. Rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 11 subjects. Cabotegravir AUC, Cmax and C24 increased by 12%, 5% and 14%; rilpivirine AUC, Cmax and C24 decreased by 1%, 4% and 8%, respectively. These results support coadministration of rilpivirine with cabotegravir as either oral or long-acting depot injection regimens.

Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Ford SL, Gould E, Chen S, et al. Antimicrob Agents Chemother. 2013;57(11):5472-7.

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Rilpivirine/ Emtricitabine/Tenofovir alafenamide (RPV/FTC/TAF)

Quality of Evidence: Low

Summary:

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where intensification of HIV treatment is needed, coadministration with cabotegravir would be possible from a pharmacokinetic standpoint. Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) did not significantly alter cabotegravir and rilpivirine pharmacokinetics. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively; rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. No interaction is expected with emtricitabine and tenofovir alafenamide. No dose adjustment is required.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab. Coadministration of rilpivirine and oral cabotegravir increased cabotegravir AUC, Cmax and Ctau by 12%, 5% and 14%, respectively; rilpivirine AUC, Cmax Ctau decreased by 1%, 4% and 8%. Rilpivirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria tablets is necessary when co-administered with rilpivirine.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, rilpivirine can be coadministered with cabotegravir without a dose adjustment. Coadministration of rilpivirine (25 mg once daily) and cabotegravir (30 mg once daily) was studied in 11 subjects. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively. Rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rimantadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Riociguat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Riociguat is metabolized by CYP1A1, CYP3A4, CYP2C8, CYP2J2 and is also eliminated unchanged in the bile and renally. Riociguat is a substrate of P-gp and BCRP. Cabotegravir does not inhibit or induce CYP enzymes, P-glycoprotein or BCRP at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ritonavir (RTV)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rituximab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Cabotegravir does not inhibit or induce CYPs or P-gp and BCRP at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rizatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rizatriptan is metabolized by oxidative deamination by monoamine oxidase-A (MAO-A).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rocuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rocuronium is mostly cleared in the bile although up to 30% may be excreted renally. P-gp was shown to mediate biliary excretion of rocuronium in a rat model. However cabotegravir does not inhibit P-gp at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Roflumilast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Roflumilast is metabolized by CYP3A4 and CYP1A2 to form roflumilast N-oxide, with both roflumilast and roflumilast N-oxide having PDE4 inhibitory activity. Roflumilast N-oxide is subsequently dealkylated by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ropinirole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ropinirole is metabolised predominantly by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rosiglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolized mainly by CYP2C8 and to a lesser extent by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sacubitril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sacubitril is rapidly converted to LBQ657 (active metabolite) by carboxylesterases and the active metabolite is not further metabolized to a significant extent.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Salbutamol (Albuterol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolized to the inactive salbutamol-O-sulphate. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Saw palmetto (Serenoa repens)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that Serenoa repens inhibits CYP2C9, CYP2D6 and CYP3A4 activity. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Selexipag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selexipag is hydrolysed to its active metabolite by carboxylesterase 1 (CES1). Both selexipag and its active metabolite undergo oxidative metabolism by CYP2C8 and CYP3A4. The active metabolite is also glucuronidated by UGT1A3 and UGT2B7. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Senna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolized by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Seville orange juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Seville orange juice inhibits intestinal CYP3A4. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sevoflurane

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sildenafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sildenafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sirolimus is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sitagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, P-gp), with metabolism by CYP3A4 representing a minor elimination pathway. Cabotegravir does not inhibit these transporters at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sodium nitroprusside

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. There is little potential for sodium nitroprusside to affect the disposition of antiretrovirals, or to be affected by antiretrovirals.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sodium stibogluconate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elimination of sodium stibogluconate is predominantly via renal glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sofosbuvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir is a weak inhibitor of intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sofosbuvir/Velpatasvir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir and velpatasvir are inhibitors of intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sofosbuvir/Velpatasvir/Voxilaprevir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sofosbuvir, velpatasvir and voxilaprevir are inhibitors of intestinal P-glycoprotein and BCRP. Cabotegravir is a substrate of P-glycoprotein and BCRP but inhibition of these transporters is unlikely to significantly affect cabotegravir intestinal absorption due to its high permeability.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Solifenacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Solifenacin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sorafenib is metabolized to a moderate extent by CYP3A4 and UGT1A9, UGT1A1. Sorafenib inhibits UGT1A1 and UGT1A9. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, but it is unlikely to be affected by sorafenib as coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase oral cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant.

Description:

No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. sorafenib).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Spectinomycin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Spironolactone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spironolactone is partly metabolized by the flavin containing monooxygenases. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Stanozolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol is extensively hydroxylated and conjugated followed by renal excretion. Cabotegravir does not affect these pathways.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. St John’s Wort is an inducer and therefore can reduce cabotegravir exposure. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir AUC by 59% A similar effect is expected with St John’s Wort. Therefore coadministration is contraindicated with oral cabotegravir due to potential for loss of therapeutic effect and development of resistance. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Streptokinase

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Streptomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is excreted rapidly in the urine by glomerular filtration.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Strontium ranelate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Strontium is a divalent cation and can chelate with the integrase inhibitor cabotegravir thereby reducing its absorption. It is recommended to administer strontium ranelate at least 2 hours before or 4 hours after intake of oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sufentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sufentanil undergoes extensive CYP3A4 metabolism, however, cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sulfadiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest that sulfadiazine is metabolized in part by CYP2C9. Cabotegravir does not induce or inhibit CYPs at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sulfadoxine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sulfasalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. Multiple mechanisms are thought to be involved in sulfasalazine metabolism including acetylation, hydroxylation, and glucuronidation. There is, therefore, low potential for clinically significant interactions with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sulpiride

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sumatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sumatriptan is eliminated primarily by monoamine oxidase A-mediated metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sunitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sunitinib is metabolized by CYP3A4. However, cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Suramin sodium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as suramin appears to be eliminated predominantly unchanged via renal glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Suxamethonium (Succinylcholine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Suxamethonium is hydrolysed by plasma cholinesterase.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tacrolimus is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tadalafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tadalafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tamoxifen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tamsulosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on limited data for metabolism and clearance a clinically significant interaction is unlikely. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tapentadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tapentadol is mainly glucuronidated by UGT1A6, UGT1A9 and UGT2B7. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tazobactam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is only minimally metabolised and is eliminated renally via glomerular filtration and active secretion by OAT1/3. Cabotegravir does not cause clinically relevant inhibition of OAT1/OAT3.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Telbivudine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telbivudine is eliminated primarily by urinary excretion as unchanged drug. The renal clearance of telbivudine approaches normal glomerular filtration rate, suggesting that filtration is the main mechanism of excretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telithromycin is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Telmisartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as telmisartan is mainly glucuronidated by UGT1A3. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Temazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Temsirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temsirolimus is metabolized by CYP3A4 and inhibits this same enzyme. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tenofovir alafenamide (HBV)

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tenofovir-DF (TDF)

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Terazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terazosin is extensively metabolized in the liver possibly via CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolized by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Terfenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terfenadine undergoes extensive metabolism by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tetracaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Absorbed tetracaine is predominantly metabolised by pseudocholinesterases in the plasma.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tetracyclines

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Thalidomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as thalidomide is cleared by non-enzymatic hydrolysis.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Theophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolized by CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Thiamine (Vitamin B1) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. A pharmacokinetic interaction is unlikely with thiamine itself. However, thiamine can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Thiopental

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although pentobarbital (a potent inducer of hepatic microsomal drug metabolism) is formed during thiopental metabolism, levels do not reach the therapeutic range. Therefore, cabotegravir pharmacokinetics are unlikely to be affected significantly by coadministration with thiopental.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thioridazine is a moderate inducer. Based on the drug-drug interaction study rifabutin (also a moderate inducer), the decrease in cabotegravir exposure after intramuscular administration is expected to be not clinically relevant. No dose adjustment is required.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tiagabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiagabine is metabolised by CYP3A4/5. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tiapride

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ticagrelor undergoes extensive CYP3A4 metabolism and is only a mild inhibitor of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Timolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tinidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinidazole is partly metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tiotropium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiotropium bromide is predominantly excreted unchanged in the urine. Metabolism by CYP2D6 and CYP3A4 is only a minor role in its elimination.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tizanidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Tizanidine is metabolised by CYP1A2, which is not inhibited or induced by cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolized by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 having a major role in CYP2D6 poor metabolisers. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Topiramate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topiramate is mainly eliminated by renal elimination in unchanged form (up to 60% of the dose) and partly by oxidation. Weak induction of CYP isozymes has been observed with higher doses of topiramate. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Topotecan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topotecan undergoes both hepatic and renal elimination. Hepatic elimination involves mainly non-enzymatic hydrolysis and, to a minor extent, CYP mediated N-demethylation as well as glucuronidation. Renal elimination is by both active secretion (mainly via OAT3) and glomerular filtration. Furthermore, topotecan is a substrate for P-gp and BCRP. Cabotegravir does not inhibit or induce CYP enzymes or drug transporters at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Torasemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolized mainly by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Toremifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Toremifene is mainly metabolized by CYP3A4 to N-demethyltoremifene. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolized by CYPs 3A4, 2B6, and 2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trandolapril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tranexamic acid

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tranylcypromine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trazodone is primarily metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Treprostinil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Treprostinil is mainly metabolized by CYP2C8 and to a lesser extent by CYP2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Triamcinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamcinolone is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Triazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Triclabendazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triclabendazole and its active sulfoxide metabolite were shown to inhibit CYP3A4 in vitro. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trimethoprim/Sulfamethoxazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trimipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolized mainly by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Triptorelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triptorelin metabolism in humans is unknown but possibly involves degradation by peptidases.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trospium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trospium is minimally metabolized and is mainly eliminated unchanged renally, in part by OCT2. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Turmeric (Curcuma longa)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, but curcumin and/or turmeric extracts had no significant effect on the pharmacokinetics of probe drugs for various UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Ulipristal is metabolized mainly by CY3A4 and to a lesser extent by CYPs 1A2 and 2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Umeclidinium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Umeclidinium bromide is mainly metabolized by CYP2D6 and is a substrate of P-gp. Cabotegravir does not inhibit or induce CYP enzymes or P-glycoprotein at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ursodeoxycholic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is metabolized by UGT1A1 and to a lesser extent by UGT1A9. Ursodeoxycholic acid is conjugated with glycine or taurine in the liver and secreted into bile. In vitro studies suggest that ursodeoxycholic acid is a CYP3A inducer however there is no evidence for UGT1A1 or UGT1A9 induction.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valaciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valaciclovir is converted to aciclovir, which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valerian

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as valsartan is eliminated unchanged mostly through biliary excretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vancomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vancomycin is excreted unchanged via renal glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vardenafil (Erectile Dysfunction)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vardenafil is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Varenicline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Varenicline is eliminated unchanged by the kidneys via glomerular filtration and active tubular secretion by OCT2. Cabotegravir does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vecuronium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vecuronium is partly deacetylated and partly cleared in the bile as parent compound.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolized by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Verapamil is metabolised mainly by CYP3A4 and is a moderate inhibitor of CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vigabatrin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vilanterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vilanterol is metabolized by CYP3A4 and is a substrate of P-gp. Cabotegravir does not inhibit or induce CYP enzymes or P-glycoprotein at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vildagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vildagliptin is inactivated via non-CYP mediated hydrolysis.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vinblastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vinblastine is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. In vitro data suggest that vinblastine activates PXR and therefore has potential inducing properties. No significant effect is expected on cabotegravir based on the drug interaction study with rifabutin (a moderate inducer).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vincristine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vincristine is metabolized by CYP3A5/4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vinorelbine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vinorelbine is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Tocopherol (Vitamin E) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. A pharmacokinetic interaction is unlikely with vitamin E itself. However, vitamin E can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Voriconazole is a strong inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vorinostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Vorinostat is mainly metabolised by glucuronidation (UGT2B17) and hydrolysis followed by B oxidation (non CYP-mediated). Cabotegravir does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vortioxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vortioxetine is mainly metabolized by CYP2D6 and to a lesser extent by CYP2C9 and CYP3A4/5. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Warfarin is a mixture of enantiomers which are metabolized by different cytochromes. R-warfarin is primarily metabolized by CYP1A2 and 3A4. S-warfarin (more potent) is metabolized by CYP2C9. Cabotegravir does not inhibit or induce CYPs at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Xipamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 90% of xipamide is excreted in the urine, mainly as unchanged drug (50%) and glucuronides (30%).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolized by aldehyde oxidase and to a lesser extent by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zanamivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small amount of the orally inhaled zanamivir is systemically absorbed. Absorbed zanamivir is excreted unchanged in the urine whereas unabsorbed zanamivir is excreted in the faeces.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zidovudine (AZT, ZDV)

Quality of Evidence: Very Low

Summary:

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

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ziprasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zoledronic acid (Zoledronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Zoledronic acid is eliminated unchanged renally. (Note, caution is required if given with calcium supplements as cabotegravir may be subject to chelation which may result in reduced cabotegravir concentrations.)

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zolmitriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolmitriptan is metabolized by CYP1A2 and the N-demethylated metabolite (active) undergoes further metabolism by MAO-A. Cabotegravir does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9 and CYP1A2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zonisamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zonisamide is metabolized partly by CYP3A4 and also by N-acetyl-transferases and conjugation. Zonisamide is a weak inhibitor of P-gp but is unlikely to have a significant effect on cabotegravir exposure. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zopiclone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zotepine is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolized by sulphoxidation, N-dealkylation (by CYP2D6 and CYP3A4) and glucuronidation. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Oral nutritional supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Oral nutritional supplements contain polyvalent cations. Cabotegravir concentrations may decrease due to chelation with polyvalent cations. Oral nutritional supplements should be administered at least 2 hours before or 4 hours after oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cedazuridine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Decitabine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Azacitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Conjugated estrogens

Quality of Evidence: Very Low

Summary:

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Cabotegravir does not inhibit or induce drug metabolizing enzymes. In addition, no interaction is expected with progestogens administered as part of HRT. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Medroxyprogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brentuximab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with cabotegravir. MMAE is a substrate of CYP3A4 and P-gp, but no interaction is expected as cabotegravir has no inhibitory or inducing effects on CYPs and brentuximab vedotin has no inhibitory or inducing effects on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Midazolam (buccal)

Quality of Evidence: Very Low

Summary:

Coadministration with buccal midazolam has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) did not alter midazolam pharmacokinetics to a clinically significant extent (Cmax and AUC increased by 9% and 10%, n=12). No significant interaction is expected with buccal administration of midazolam as pharmacokinetic interactions are more pronounced for oral as compared to buccal or parenteral midazolam as CYP3A4 enzymes are also present in the upper gastro-intestinal tract.

Description:

In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Based on drug interaction study results, midazolam can be coadministered with cabotegravir without a dose adjustment. Coadministration of midazolam (3 mg) and cabotegravir (30 mg once daily) was studied in 12 subjects. Midazolam Cmax and AUC increased by 9% and 10%.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral midazolam (3 mg single dose) was studied in 12 subjects and was found not to significantly affect midazolam pharmacokinetics (AUC and Cmax increased by 8% and 9%).

Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Reese MJ, Bowers GD, Humphreys JE, et al. Xenobiotica. 2016;46(5):445-56.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sotrovimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Sotrovimab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Sotrovimab is not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nirmatrelvir/ritonavir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure given induction does not reach maximal effect due to the short duration of nirmatrelvir/ritonavir treatment. Cabotegravir is not expected to alter concentrations of other antiviral products.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Whey Protein

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Whey protein is rapidly digested and absorbed as essential amino acids for use in physiological processes. Excess whey protein can be excreted in the urine by the kidneys. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Whey protein is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enobosarm (Ostarine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enobosarm is primarily excreted in faeces as unchanged drug, with CYP3A4, UGT1A1 and UGT2B7 having a minor role in enobosarm metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Enobosarm is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bulevirtide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bulevirtide is catabolized by peptidases and elimination occurs through binding to NTCP (a bile salt liver transporter serving as HDV/HBV entry receptor). Cabotegravir does not interfere with this elimination pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ecdysterone (20-hydroxyecdysone, 20E)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ecdysterone has poor bioavailability and is predominantly metabolised once it reaches the gut microbiota. Unchanged ecdysterone and ecdysterone metabolites are excreted in both urine and faeces. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Ecdysterone is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Telavancin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telavancin is primarily excreted as unchanged drug in the urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Rilpivirine is unlikely to affect cabotegravir elimination. Telavancin is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rolapitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rolapitant is metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4. Rolapitant is unlikely to have a clinically relevant effect cabotegravir metabolism.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Enzalutamide

Summary:

Coadministration has not been studied but is not recommended. Enzalutamide is primarily metabolized by CYP2C8 and induce UGTs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and has no inducing effects on CYPs. Based on a drug interaction study with rifampicin (another inducer of UGTs), coadministration is expected to significantly reduce cabotegravir concentrations which may result in loss of therapeutic effect and development of resistance. Enzalutamide has a long half-life (5.8 days), therefore a minimum of 2 weeks (but preferably 4 weeks) cessation period is recommended prior to initiation of cabotegravir due to the persisting inducing effect upon discontinuation of a strong inducer.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Creatine monohydrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Creatine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Caffeine (anhydrous powder)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not affect CYP1A2 and caffeine is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Beta-alanine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Beta-alanine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Branched chain amino acids (BCAAs; leucine, isoleucine, valine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. BCAAs are unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nilutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nilutamide is metabolised by CYP2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alprostadil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Alprostadil is unlikely to affect UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bilastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Bilastine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bimekizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Daridorexant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daridorexant is mainly metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Daridorexant is unlikely to have a significant effect on UGT1A1 or UGT1A9. Cabotegravir does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Deflazacort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Deflazacort and 21-desdeflazacort do not inhibit or induce UGT1A1 or UGT1A9. Cabotegravir does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Entacapone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entacapone undergoes isomerization followed by glucuronidation of both the E and Z isomers; ~90% of the dose is then excreted in faeces. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Entacapone does not inhibit or induce UGT1A1 or UGT1A9. Cabotegravir does not inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Guselkumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Guselkumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pentosan polysulfate sodium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pentosan polysulfate sodium is metabolised by desulfation in the liver and depolymerisation in the kidney. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Pentosan polysulfate sodium is unlikely to affect UGT1A1 or UGT1A9. Metabolic drug-drug interactions are not expected with desulfation and depolymerisation reactions.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sodium zirconium cyclosilicate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium zirconium cyclosilicate is not absorbed or metabolised by the body and is eliminated via the faeces. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Sodium zirconium cyclosilicate is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Doxylamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolised primarily by CYP2D6, CYP1A2 and CYP2C9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Doxylamine is unlikely to have a clinically significant effect on cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosaprepitant is a prodrug of aprepitant and when administered intravenously is rapidly converted to aprepitant. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Aprepitant shows a weak inducing effect on UGT on day 8 which is clinically insignificant by two weeks. Any transient change in cabotegravir exposure is unlikely to be clinically significant.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flutamide is predominantly metabolised by CYP1A2 and to a lesser extent by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Furazolidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furazolidone is primarily metabolised by nitro-reduction to an aminofuran derivative. Detoxification and subsequent renal excretion occur mainly via glutathione conjugation. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Furazolidone is unlikely to affect UGT1A1 or UGT1A9. Cabotegravir is unlikely to affect furazolidone metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Riboflavin (Vitamin B2) [alone]

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Idarubicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Idarubicin is converted to idarubicinol by aldo-keto reductase. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect idarubicin metabolism. Idarubicin is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Rilpivirine/ Emtricitabine/Tenofovir-DF (RPV/FTC/TDF)

Quality of Evidence: Very Low

Summary:

Eviplera/Complera (rilpivirine, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where intensification of HIV treatment is needed, coadministration with cabotegravir would be possible from a pharmacokinetic standpoint. Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) did not significantly alter cabotegravir and rilpivirine pharmacokinetics. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively; rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. No interaction is expected with emtricitabine and tenofovir-DF. No dose adjustment is required.

Description:

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

Complera US Prescribing Information, Gilead Sciences Inc, November 2019.

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 11 subjects. Cabotegravir AUC, Cmax and C24 increased by 12%, 5% and 14%; rilpivirine AUC, Cmax and C24 decreased by 1%, 4% and 8%, respectively. These results support coadministration of rilpivirine with cabotegravir as either oral or long-acting depot injection regimens.

Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Ford SL, Gould E, Chen S, et al. Antimicrob Agents Chemother. 2013;57(11):5472-7.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Betamethasone (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of betamethasone (for example, ointment, cream, lotion, emollient, foam).

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Activated charcoal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and orally administered cabotegravir should be separated by 4 hours. [Note: this interaction is not specific for orally administered cabotegravir, but for any oral medication taken with activated charcoal.]

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nicotine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotine is metabolised mainly by CYP2A6 which is not affected by cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Netupitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Netupitant is metabolized primarily by CYP3A4 and to a lesser extent by CYP2C9 and CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Netupitant is unlikely to affect UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivacaftor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivacaftor is primarily metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4. Ivacaftor is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Selegiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selegiline is metabolised mainly by CYP2B6 with some contribution from CYP3A4 and CYP2A6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Selegiline is unlikely to affect CYP3A4 or UGT1A1. Cabotegravir does not inhibit or induce CYP2B6, CYP3A4 or CYP2A6.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tobramycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tobramycin is not metabolised and is primarily eliminated unchanged by glomerular filtration. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivacaftor/Lumacaftor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lumacaftor is primarily excreted unchanged in the faeces. Ivacaftor is primarily metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4. Lumacaftor/ivacaftor is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is mainly metabolised by CYP2D6, with minor contributions from CYP3A4 and CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pexidartinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pexidartinib is metabolized by CYP3A4 and UGT1A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pemigatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pemigatinib is mainly metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pancreatic enzymes (pancrelipase, pancreatin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with pancreatic enzyme preparations containing amylase, lipase and protease.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lymecycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lymecycline is not metabolised and is excreted unchanged by renal and biliary routes.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Ferrous sulfate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as iron resulting in a reduced absorption of cabotegravir. Ferrous sulfate should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methocarbamol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9. Methocarbamol is metabolized in the liver by dealkylation, hydroxylation, and glucuronidation. Methocarbamol is unlikely to be a substrate or inhibitor of CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ubrogepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ubrogepant is metabolized mainly by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivacaftor/Tezacaftor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivacaftor is primarily metabolized by CYP3A4, and tezacaftor by CYP3A4 and CYP3A5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4/5. Ivacaftor/tezacaftor is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tocilizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on tocilizumab is expected as it is an IL-6 receptor monoclonal antibody and likely undergoes elimination via binding to its target antigen. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ivacaftor/Tezacaftor/ Elexacaftor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivacaftor is primarily metabolised by CYP3A4. Tezacaftor and elexacaftor are metabolised by CYP3A4 and CYP3A5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4/5. Ivacaftor/tezacaftor/elexacaftor is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ketoprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketoprofen is mainly metabolized by multiple UGTs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Drospirenone (POP)

Quality of Evidence: Very Low

Summary:

Coadministration with a drospirenone progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Norgestimate (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with norgestimate as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is deacetylated to the active metabolite norelgestromin which is then metabolised to norgestrel, possibly by CYP3A4. Cabotegravir does not inhibit or induce drug metabolizing enzymes. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ashwagandha (Withania somnifera)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Apremilast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9, however, apremilast has no inhibitory or inducing effects on drug metabolizing enzymes or drug transporters. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Iron supplements (infusion/injection)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Integrase inhibitors are unlikely to be affected by chelation when iron supplements are administered as an injection or infusion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cabozantinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabozantinib is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9. Cabozantinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rimegepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimegepant is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9 and is a substrate of P-gp and BCRP. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Infigratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Infigratinib is mainly metabolized by CYP3A4 and to a lesser extent by FMO3. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Infigratinib is unlikely to affect drugs metabolized by UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ibrutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibrutinib is metabolised primarily by CYP3A4 and to a minor extent by CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Ibrutinib is unlikely to affect drugs metabolized by UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glasdegib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glasdegib is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C8 and UGT1A9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Glasdegib is unlikely to have a clinically significant effect on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Gilteritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gilteritinib is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fostamatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostamatinib is metabolised in the gut by alkaline phosphatase to the major active metabolite, R406, which is then metabolised by CYP3A4 and UGT1A9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. R406 is considered as a weak UGT1A1 inhibitor in vivo and is unlikely to have a clinically significant effect on cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etanercept

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etanercept is a TNF-alpha inhibitor and is eliminated via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hyoscine hydrobromide (Scopolamine hydrobromide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine, derived from hyoscine hydrobromide, is metabolized by multiple pathways including CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hyoscine (Scopolamine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine is metabolized by multiple pathways including CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Sevelamer

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sevelamer is a resin not absorbed from the GI tract that may affect the bioavailability of other medicinal products. In the absence of data, when administering any medicinal product where a reduction in the bioavailability could have a clinically significant effect on safety or efficacy, the medicinal product should be administered at least one hour before or three hours after sevelamer. [Note: this interaction is not specific for cabotegravir administered orally, but for any medication taken with sevelamer].

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Darolutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tolvaptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolvaptan is extensively metabolized in the liver almost exclusively by CYP3A. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Methotrexate (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been assessed in clinical studies. Cabotegravir inhibits in vitro the renal transporters OAT1 and OAT3. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion via OAT1, OAT3. Although PBPK modelling suggests that OAT1/OAT3 inhibition is not clinically relevant (<25% mean increase in exposure of OAT1 or OAT3 substrates with oral cabotegravir), the European product label for cabotegravir recommends caution when coadministering with a narrow therapeutic index drug such as methotrexate. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Description:

Caution is advised when co-dosing with narrow therapeutic index OAT1/3 substrate drugs (e.g. methotrexate).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Moxonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxonidine is only minimally metabolized and is eliminated renally, mainly as unchanged moxonidine.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rezafungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rezafungin is primarily eliminated unchanged by faecal excretion. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect rezafungin elimination. Rezafungin is unlikely to inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pizotifen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pizotifen is glucuronidated by UGT2B10. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Pizotifen is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Repotrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repotrectinib is primarily metabolized by CYP3A4 followed by secondary glucuronidation. Repotrectinib is also a P-gp substrate. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4 or UGTs. Repotrectinib is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Moexipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moexipril is rapidly converted to the active metabolite moexiprilat, likely via carboxylesterases . Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect moexipril metabolism. Moexipril is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Elagolix

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elagolix is primarily metabolized by CYP3A4 and is a substrate of P-gp and OATP1B1. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4. Elagolix is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valganciclovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valganciclovir is rapidly hydrolysed to ganciclovir. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Valganciclovir and ganciclovir are unlikely to affect UGT1A1 and UGT1A9. Cabotegravir is unlikely to affect ganciclovir elimination

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Avatrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nizatidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nizatidine is primarily eliminated via tubular secretion and glomerular filtration in urine. Cabotegravir does not cause clinically relevant inhibition of renal transporters. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Etoricoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoricoxib is metabolised by CYPs 3A4 (main), 2D6, 2C9, 1A2 and 2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clotrimazole (pessary, troche)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clotrimazole undergoes hepatic metabolism (likely via CYP3A4) and is a moderate inhibitor of CYP3A4. Coadministration is unlikely to alter clotrimazole exposure and no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lenvatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenvatinib is extensively metabolised by multiple enzymes, mainly CYP3A4 and aldehyde oxidase. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Inhibition of intestinal UGT1A1 by lenvatinib is unlikely to significantly alter cabotegravir exposure as coadministration of atazanavir (a strong inhibitor of UGT1A1) was predicted to increase cabotegravir exposure by 11%.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Terbutaline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbutaline is eliminated primarily as sulfate and glucuronide conjugates with oral dosing and excreted mainly unchanged with inhalation dosing.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brimonidine

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Letermovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Letermovir is partly eliminated by glucuronidation via UGT1A1/3, but is largely eliminated unchanged in the bile. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. The effect of letermovir on UGT1A1 is unclear; the product label mentions it could potentially increase or decrease exposure of UGT1A1 substrates. However, inhibition of UGT1A1 would not require a dosage adjustment of cabotegravir based on the drug-drug interaction study with atazanavir. Furthermore, no dosage adjustment of cabotegravir would be needed if letermovir has a moderate inducing effect on UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Thiotepa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thiotepa is rapidly metabolised by CYP3A4 and CYP2B6 to the active alkylating metabolite TEPA. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Thiotepa is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Copanlisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Copanlisib does not inhibit or induce UGT1A1 or UGT1A9.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Ferrous fumarate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations such as iron resulting in a reduced absorption of cabotegravir. Ferrous fumarate should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Drotaverine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drotaverine is metabolised in the liver by O-deethylation. Clinically relevant pharmacokinetic interactions have not been reported. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dimethyl fumarate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Colesevelam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract and is not metabolised. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after orally administered cabotegravir to minimize the risk of reduced absorption.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cytisine (Cytisinicline)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Coenzyme Q10 (Ubidecarenone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ascorbic Acid (Vitamin C) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Cabotegravir does not interfere with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Romidepsin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Romidepsin is mainly metabolised by CYP3A4 with a minor contribution from CYPs 3A5, 1A1, 2B6 and 2C19, and is a substrate of P-gp. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Romidepsin is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ropivacaine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ropivacaine is mainly metabolised by CYP1A2, with CYP3A4 having a minor role. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP1A2. Ropivacaine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Busulfan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect busulfan metabolism. Busulfan is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Indometacin (Indomethacin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indometacin is metabolized predominantly by acylation followed by glucuronidation (mainly UGT2B7 and partly by UGT1A9). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Indometacin is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Dolutegravir/ Lamivudine/ Tenofovir-DF (DTG/3TC/TDF; TLD)

Quality of Evidence: Very Low

Summary:

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desmopressin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. No metabolic drug interactions are expected with desmopressin.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enfortumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enfortumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism. MMAE is a substrate of CYP3A4 (and possibly CYP2D6) and P-gp. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trametinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trametinib is mainly metabolised by deacetylation; metabolism by CYP3A4 is considered to be a minor pathway. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Trametinib is unlikely to affect the pharmacokinetics of other medicinal products.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hydroxychloroquine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxychloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Thiamine (Vitamin B1) [alone]

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tocopherol (Vitamin E) [alone]

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Terlipressin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terlipressin is metabolized by various peptidases in the liver and kidney.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Sucralfate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Sucralfate is only minimally absorbed from the gastrointestinal tract. Sucralfate contains aluminium and may decrease cabotegravir concentrations due to chelation with polyvalent cations. Sucralfate should be administered at least 2 hours before or 4 hours after oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Erdafitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erdafitinib is primarily metabolised by CYP2C9 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desvenlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is mainly metabolized by glucuronidation (several UGT enzymes) and to a minor extent through oxidative metabolism by CYP3A4 and CYP2C19. Renal elimination of unchanged desvenlafaxine also constitutes an important route of elimination. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Desvenlafaxine is not expected to significantly inhibit or induce CYP3A4 at the dose in clinical use.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fostemsavir (FTR)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ospemifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ospemifene is primarily metabolised by CYP3A4 and CYP2C9; CYP2C19 and UGTs 1A3, 2B7, 1A1 and 1A8 also contribute to its metabolism. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Ospemifene and its major metabolite inhibit UGT1A3 and UGT1A9 but a clinically significant effect on cabotegravir is not expected. A PBPK model predicted coadministration with mefenamic acid (a strong UGT1A9 inhibitor) to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant.

Description:

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pretomanid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pretomanid is metabolized in the liver via multiple reductive and oxidative pathways with CYP3A4 mediated metabolism representing 20% of its metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valproic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valproic acid circulates in plasma as the valproate ion. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Valproate semisodium (Divalproex sodium)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valproate semisodium (divalproex semisodium) is a stable coordination compound comprised of sodium valproate and valproic acid and dissociates to the valproate ion in the gastrointestinal tract. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Entrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entrectinib is mainly metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Semaglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Semaglutide is metabolized by the enzyme neutral endopeptidase. Semaglutide (oral and injectable) delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, based on available interaction studies, a clinically relevant effect is not expected with cabotegravir. Note: food, beverages and oral medicinal products can interfere with the absorption of oral semaglutide. Therefore, patients must wait at least 30 minutes after taking oral semaglutide before taking any other oral medicinal product.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Apalutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 and induces UGTs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs. Based on a drug interaction study with rifampicin (another inducer of UGTs), coadministration is expected to significantly reduce cabotegravir concentrations which may result in loss of therapeutic effect and development of resistance. Apalutamide has a long half-life (3 days), therefore a minimum of 2 weeks (but preferably 4 weeks) cessation period is recommended prior to initiation of cabotegravir due to the persisting inducing effect upon discontinuation of a strong inducer.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Omega-3 fatty acids [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Omega-3 fatty acids are eliminated via oxidation similar to dietary fatty acids. A pharmacokinetic interaction is unlikely with omega-3 fatty acids alone. However, omega-3 fatty acids can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fosfomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosfomycin is excreted unchanged mainly via the kidney by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Afatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Afatinib is mainly eliminated unchanged in the faeces and does not inhibit or induce UGTs. Cabotegravir is metabolized mainly by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Risedronic acid (Risedronate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risedronate is not metabolized and is excreted unchanged primarily by the kidney. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Risedronate does not induce or inhibit hepatic drug metabolizing enzymes such as UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cinacalcet

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bendamustine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Binimetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce UGTs and CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brigatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brigatinib is metabolised by CYP2C8 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Capmatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Capmatinib is primarily metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cobimetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Crizotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Crizotinib is mainly metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Daratumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Durvalumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Durvalumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ipilimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ipilimumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pembrolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pembrolizumab is an IgG4-kappa monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 No metabolic drug interactions are expected with pembrolizumab.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fulvestrant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of fulvestrant has not been fully evaluated: in vitro studies suggest the involvement of CYP3A4, however, non-P450 routes appear to be more predominant in vivo. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP3A4. Fulvestrant does not inhibit CYP enzymes and there are no known drug-drug interactions.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Methylergometrine (Methylergonovine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylergometrine is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Methylergometrine is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fezolinetant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fezolinetant is primarily metabolised by CYP1A2 and to a lesser extent by CYP2C9 and CYP2C19. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Naratriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naratriptan is metabolised by a wide range of CYP enzymes and is mainly excreted in urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Significant metabolic drug interactions with naratriptan are not anticipated.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Galcanezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Galcanezumab is a monoclonal IgG4 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Erenumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erenumab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eptinezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eptinezumab is a monoclonal IgG1 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Homeopathic remedies

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence that homeopathic remedies interact with conventional medicines, provided they are from a reputable source, and of the strength stated. However, caution may be required as some remedies termed “low potency” are less dilute, and some remedies may contain alcohol.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vedolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vedolizumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Interactions with drug metabolizing enzymes or drug transporters are unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tinzaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is partially metabolised by desulfation and depolymerization, and then renally excreted. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Raloxifene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raloxifene undergoes hepatic glucuronidation (by UGT1A1 and UGT1A9) and extra-hepatic glucuronidation (by UGT1A8 and UGT1A10). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect drugs metabolized by UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bumetanide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Flupentixol (Flupenthixol)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flupentixol is metabolised by sulfoxidation and dealkylation and is a substrate of UGT. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Flupentixol is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tofacitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tofacitinib undergoes hepatic metabolism (70%) primarily by CYP3A4 with a minor contribution from CYP2C19, and is eliminated renally (30%). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Tofacitinib does not affect UGTs. Cabotegravir is unlikely to affect tofacitinib metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rucaparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rucaparib is primarily metabolised by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Rucaparib is a weak inhibitor of UGT1A1 but a clinically significant effect on cabotegravir is not expected.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Procyclidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Little is known about procyclidine metabolism but it is likely to be metabolized by CYP450s and glucuronidated. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect procyclidine metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Orphenadrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Orphenadrine is extensively metabolized (limited information on metabolic pathway). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect orphenadrine metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Minoxidil (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minoxidil is a substrate of UGTs (the specific UGTs have not been well described). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. The likelihood of clinically significant interactions is low as only 1-2% of a topically applied minoxidil dose is absorbed.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Minoxidil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minoxidil is a substrate of UGTs (the specific UGTs have not been well described). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Minoxidil and cabotegravir are unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Benzatropine (Benztropine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lomitapide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lomitapide is predominantly metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Lomitapide is unlikely to affect UGTs. Cabotegravir is unlikely to affect CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Deferasirox

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Deferasirox and cabotegravir are unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pertuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pertuzumab is an IgG1 monoclonal antibody and is eliminated via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. No metabolic drug interactions are expected with pertuzumab.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Idelalisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Idelalisib is metabolised primarily by aldehyde oxidase, and to a lesser extent by CYP3A4 and UGT1A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Golimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Golimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Bismuth subsalicylate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Bismuth subsalicylate is unlikely to affect UGTs. However, cabotegravir may be subject to chelation by high concentrations of trivalent bismuth cations which may result in reduced cabotegravir concentrations. Bismuth subsalicylate should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Macrogol (Polyethylene glycol, PEG 3350, PEG 4000)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Macrogol is unabsorbed from the gastrointestinal tract and is excreted, unaltered, in faeces. Any macrogol that does enter the circulation is excreted in urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. However, the absorption of other oral medications may be reduced due to increased gastrointestinal transit with macrogol. Do not take macrogol within two hours of taking another oral medication. [Note: this interaction is not specific for oral cabotegravir but for any oral medication taken with macrogol.]

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Rivastigmine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivastigmine is extensively metabolised by cholinesterase-mediated hydrolysis with minimal involvement of CYP450 enzymes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Belimumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dupilumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dupilumab is an IgG4 monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. No metabolic drug interactions are expected with dupilumab.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ruxolitinib (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ruxolitinib is metabolized by CYP3A4 (major) and CYP2C9 (minor). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ruxolitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ruxolitinib is metabolized by CYP3A4 (major) and CYP2C9 (minor). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nitazoxanide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide, which is subsequently glucuronidated. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Canakinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Galantamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Galantamine is metabolised mainly by CYP2D6 and CYP3A4, but is also glucuronidated and excreted in urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alemtuzumab (Cancer therapy)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Necitumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Necitumumab is an IgG1 monoclonal antibody and is eliminated via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nivolumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nivolumab is a monoclonal IgG4 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Hyoscine butylbromide (Butylscopolamine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hyoscine butylbromide has poor systemic absorption and acts locally in the intestine. The main metabolic pathway is the hydrolytic cleavage of the ester bond. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Baricitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Melatonin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Melatonin is metabolized mainly by CYP1A2, with CYP1A1 and CYP2C19 involved to a minor extent. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Certolizumab pegol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Favipiravir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Favipiravir undergoes no CYP-mediated metabolism but is mainly metabolised by aldehyde oxidase with UGT having a minor role. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Favipiravir does not affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Maribavir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maribavir is primarily eliminated by CYP3A4 (at least 35%), with secondary contribution from CYP1A2 (no more than 25%), and some contribution from multiple UGTs (low). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4. Maribavir is unlikely to have a clinically significant effect on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cenobamate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit UGTs and was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dronedarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronedarone is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4 but no effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bempedoic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Bempedoic acid does not inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Icosapent ethyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Icosapent ethyl is eliminated via beta-oxidation similar to dietary fatty acids.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tirzepatide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tirzepatide is metabolized by proteolytic cleavage. Tirzepatide delays gastric emptying, and has the potential to impact the absorption of concomitantly administered oral medications. However, based on available interaction studies, a clinically relevant effect is not expected with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Anakinra

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lisdexamfetamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisdexamfetamine is a prodrug of dexamfetamine and is not metabolized by CYP enzymes. Dexamfetamine is metabolized by CYP2D6 to some extent, whereas a large part is excreted unchanged. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pralsetinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pralsetinib is metabolized by CYP3A4 and UGT1A4 and to a lesser extent by CYP2D6 and CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isosorbide mononitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isosorbide mononitrate is completely absorbed and is not subject to first pass metabolism by the liver. It is denitrated and glucuronidated to inactive metabolites before being excreted mainly in the urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Only ~25% of an isosorbide mononitrate dose is glucuronidated, there is therefore little potential for clinically significant interactions with cabotegravir via competition for glucuronidation pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Opipramol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Opipramol is metabolized by CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Panitumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Panitumumab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 No drug interactions are expected with panitumumab.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Olaratumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olaratumab is a monoclonal IgG1 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 No interactions are expected with olaratumab and substrates, inhibitors or inducers of CYP enzymes or other metabolising enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ofatumumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofatumumab is a fully human monoclonal IgG1 antibody; elimination occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. No interactions are expected with ofatumumab and substrates, inhibitors or inducers of CYP enzymes, other metabolising enzymes or transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Omega-3 fatty acids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omega-3 fatty acids are eliminated via oxidation similar to dietary fatty acids.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Daptomycin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bicalutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs. Bicalutamide inhibited UGT1A9 in vitro but is unlikely to have a clinically significant effect on cabotegravir. A PBPK model predicted coadministration with mefenamic acid (a strong UGT1A9 inhibitor) to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant.

Description:

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Meloxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meloxicam is metabolised mainly by CYP2C9, with a minor contribution from CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alpelisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Amivantamab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Abrocitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abrocitinib is mainly metabolized by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Cabotegravir is metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Abrocitinib is not expected to have a clinically relevant effect on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Cabotegravir is metabolized mainly by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atezolizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Avapritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Axitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYPs or UGTs at clinically relevant concentrations. Axitinib does not inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ispaghula husk

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Ispaghula husk passes predominantly unchanged through the gastrointestinal tract and there is little opportunity for marked absorption into or metabolism by the body. The mode of action of ispaghula husk is physical and does not depend on absorption into the systemic circulation. However, ispaghula husk may delay or reduce gastrointestinal absorption of other drugs and it is advisable to separate administration of ispaghula husk and orally administered drugs by 1 hour. [Note: this interaction is not specific for cabotegravir, but for any oral medication taken with ispaghula husk.]

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Psyllium husk

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Psyllium husk passes predominantly unchanged through the gastrointestinal tract and there is little opportunity for marked absorption into or metabolism by the body. The mode of action of psyllium husk is physical and does not depend on absorption into the systemic circulation. However, psyllium husk may delay or reduce gastrointestinal absorption of other drugs and it is advisable to separate administration of psyllium husk and orally administered drugs if possible. [Note: this interaction is not specific for cabotegravir, but for any oral medication taken with psyllium husk.]

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lurasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mebeverine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mebeverine is mainly metabolized by esterases. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Risankizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risankizumab is primarily metabolised through catabolic pathways similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ceritinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceritinib is metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Dabrafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Dabrafenib is a strong inducer of CYP3A4 and may induce UGTs and has the potential to decrease cabotegravir exposure which may result in loss of therapeutic effect.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dacomitinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYPs. Dacomitinib inhibits UGT1A1 but no significant interaction is expected with cabotegravir. Coadministration of cabotegravir with the strong UGT1A1 inhibitor atazanavir was predicted to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant. A comparable effect is expected with dacomitinib.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Duvelisib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duvelisib is metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Vemurafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vemurafenib is metabolized by CYP3A4 and is a moderate inducer of CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Infliximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Infliximab is a TNF-alpha inhibitor and is eliminated via binding to its target antigen. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ustekinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ustekinumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Zinc

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body and is excreted in the faeces with traces appearing in the urine. Coadministration may decrease cabotegravir concentrations due to chelation with the polyvalent zinc cations. Zinc should be administered at least 2 hours before or 4 hours after oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enasidenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enasidenib is metabolized by multiple CYP and UGTs enzymes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Enasidenib has no inducing effect on UGTs but inhibits UGT1A1. However, enasidenib is unlikely to significantly increase cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Encorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Encorafenib is mainly metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Encorafenib was shown to inhibit UGT1A1 in vitro however, simulations suggest that a minor to moderate interaction is expected with UGT1A1 substrates. No a priori dosage adjustment is needed for cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fedratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fedratinib is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C19 and FMO3. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Obinutuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Obinutuzumab is a monoclonal IgG antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 No interactions are expected with obinutuzumab and substrates, inhibitors or inducers of CYPs, UGTs or P-gp.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Inotuzumab ozogamicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inotuzumab ozogamicin is a humanized monoclonal antibody; elimination occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. No interactions are expected with inotuzumab ozogamicin and substrates, inhibitors or inducers of CYP enzymes, UGT enzymes or transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Elotuzumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elotuzumab is a monoclonal IgG antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 No interactions are expected with elotuzumab and substrates, inhibitors or inducers of CYP or other drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Venetoclax

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venetoclax is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sodium valproate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium valproate circulates in plasma as the valproate ion. Valproate is mainly glucuronidated by UGTs 1A6, 1A9 and 2B7 and metabolized by CYP2C9 and CYP2C19. Valproate has no inducing effects on metabolism. Cabotegravir does not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tegafur/ Gimeracil/ Oteracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tegafur is metabolised to the active compound 5-fluorouracil by CYP2A6; gimeracil and oteracil are not metabolised by CYPs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fremanezumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fremanuzemab is a monoclonal IgG2 antibody; elimination is similar to endogenous IgG and occurs primarily via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dexamethasone (doses above 16 mg)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dexamethasone is a substrate of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Dexamethasone has shown some inducing effects on UGT1A1 in vitro, however, the clinical relevance is unclear. No significant effect is expected on oral cabotegravir as indicated by a drug-drug interaction study with rifabutin (a moderate inducer).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dexamethasone (low dose; 16 mg or less)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dexamethasone is a substrate of CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Dexamethasone is a weak CYP3A4 inducer at a low dose and has shown some inducing effects on UGT1A1 in vitro, but is unlikely to have a clinically significant effect on oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Frovatriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Frovatriptan is metabolized by CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Frovatriptan is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Guggulsterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. In vitro studies suggest that guggulsterone activates PXR and therefore has the potential to induce CYP3A4 metabolism. A case report described sub-therapeutic elvitegravir/cobicistat concentrations in a HIV-infected individual with concomitant use of guggulsterone supplements. The patient was subsequently switched to a dolutegravir containing regimen while continuing the use of guggulsterone. Dolutegravir concentrations were in the range of expected concentrations suggesting that metabolism by UGT (and subsequently cabotegravir exposure) may not be impacted by guggulsterone.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Clotrimazole (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant interaction is unlikely with the topical use of clotrimazole as it is minimally absorbed

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trifluridine/Tipiracil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trifluridine is mainly metabolised by thymidine phosphorylase (TPase) to form the inactive metabolite 5-(trifluoromethyl) uracil (FTY); tipiracil is not metabolised. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tivozanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tivozanib is metabolised mainly by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Tivozanib is unlikely to affect drugs metabolized by UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Niraparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Niraparib is metabolized by carboxylesterases and UGTs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce UGT enzymes at clinically relevant concentrations. Niraparib is unlikely to have a clinically relevant effect on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Azilsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azilsartan is metabolized mainly by CYP2C9. Cabotegravir does not inhibit or induce CYP2C9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ixazomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ixazomib is extensively metabolised by multiple CYP and non-CYP enzymes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Emtricitabine/Tenofovir alafenamide for PrEP (FTC/TAF, PrEP)

Quality of Evidence: Low

Summary:

Emtricitabine and tenofovir alafenamide used as PrEP are not expected to be coadministered with antiretrovirals. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors and ibalizumab.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Enfuvirtide (ENF, T20)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Enfuvirtide undergoes catabolism to its constituent amino acids. This metabolic pathway is unlikely to be affected by coadministered drugs. The potential for metabolic interactions with enfuvirtide is low.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cemiplimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sotalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is mainly eliminated unchanged by the kidney by glomerular filtration and to a small degree by active secretion via the renal transporters OCT2 and MATE1. Cabotegravir does not cause clinically significant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Midodrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midodrine is a prodrug converted to its active metabolite desglymidodrine in various tissues. Desglymidodrine is mainly metabolized by CYP2D6 and to a lesser extent by CYP1A2. Cabotegravir is mainly metabolized by UGT1A1 and has no inhibitory or inducing effects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tesamorelin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tesamorelin is a peptide analogue which is likely eliminated by catabolism to its constituent amino acids.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ketorolac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ketorolac is partly eliminated renally and via hepatic metabolism by CYP2C8, CYP2C9 and UGT2B7. Cabotegravir is metabolized by UGT1A1 and to a lesser extent by UGT1A9. Ketorolac does not inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Octreotide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Octreotide has been reported to be heavily metabolized in the liver but the metabolic pathway is unclear. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir has no inhibitory or inducing effects on drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brincidofovir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Cabotegravir does not affect this pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tecovirimat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tecovirimat is metabolized by hydrolysis (major) and glucuronidation by UGT1A1 and UGT1A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Tecovirimat and cabotegravir do not inhibit or induce UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alirocumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alirocumab is a monoclonal antibody eliminated through binding to PCSK9 at low concentrations and through a proteolytic pathway at higher concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Yohimbine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Yohimbine is predominantly metabolized by CYP2D6 with some participation of CYP3A4 whereas cabotegravir is mainly metabolized by UGT1A1. Cabotegravir has no inhibitory effects on CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lenacapavir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Both cabotegravir and lenacapavir do not have any inhibitory or inducing effects on UGT1A1 in the range of clinically significant concentrations.

Description:

If Sunlenca is discontinued, residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods. These concentrations are not expected to affect the exposures of other antiretroviral agents that are initiated after discontinuation of Sunlenca.

Sunlenca Summary of Product Characteristics, Gilead Sciences Ltd, August 2022.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eribulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eribulin is primarily eliminated via biliary excretion and is minimally metabolized (metabolism by CYP3A4 is negligible). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Talazoparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Talazoparib undergoes minimal hepatic metabolism and is primarily excreted renally via P-gp and BCRP. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce P-gp. Talazoparib is not expected to affect drugs metabolised UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sotorasib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotorasib is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Leflunomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leflunomide is primarily metabolized to the active metabolite teriflunomide (A771726). Metabolism is not controlled by a single enzyme and has been shown to occur in microsomal and cytosolic cellular fractions. Interaction studies with the non-specific CYP inhibitor cimetidine and with the strong inducer rifampicin suggest that CYP metabolism plays a minor role in leflunomide metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Fampridine (Dalfampridine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fampridine is metabolized by CYP2E1 but is predominantly eliminated unchanged by the kidney with active secretion by OCT2. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations and does not cause clinically relevant inhibition of renal transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Asciminib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYPs or UGTs at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Selpercatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Selpercatinib is metabolized predominantly by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ribociclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ribociclib is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Ribociclib does not affect UGT enzymes.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Colestyramine (cholestyramine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for oral cabotegravir, but for any medication taken with colestyramine.]

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dexlansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexlansoprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor). Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Regorafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Regorafenib is metabolized by CYP3A4 and UGT1A9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Regorafenib and its metabolites inhibit UGT1A1 and UGT1A9 but a clinically significant effect on cabotegravir is not expected. A PBPK model predicted coadministration with mefenamic acid (a strong UGT1A9 inhibitor) to increase cabotegravir (30 mg once daily) exposure by 11% which is considered not to be clinically relevant.

Description:

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ponatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ponatinib is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8, CYP2D6 and CYP3A5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pomalidomide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pomalidomide is metabolised by CYP1A2 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pemetrexed

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pemetrexed is not appreciably metabolised and is primarily eliminated unchanged renally (70-90% recovered in 24 hours). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Panobinostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Panobinostat is metabolized by non-CYP and CYP mediated routes; approximately 40% of panobinostat is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Palbociclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palbociclib is metabolised by CYP3A and SULT2A1. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Osimertinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Osimertinib is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Olaparib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olaparib is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Olaparib inhibited UGT1A1 in vitro, however, PBPK simulations suggest this is not of clinical importance.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Neratinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Neratinib is metabolised mainly by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Cabotegravir/rilpivirine [long acting] (CAB/RPV LA)

Quality of Evidence: Very Low

Summary:

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. However, if a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (cabotegravir 30 mg and rilpivirine 25 mg once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly visit). The first dose of oral therapy should be taken approximately 1 month (or two months if administered at two-monthly intervals) after the last injection dose of cabotegravir/rilpivirine. Injection dosing should be resumed on the day oral dosing completes.

Description:

If a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (one 30 mg cabotegravir tablet and one 25 mg rilpivirine tablet once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly injection visit). For oral therapy durations greater than two months, an alternative oral regimen is recommended. The first dose of oral therapy should be taken one month (or approximately two months), +/- 7 days, after the last injection doses of cabotegravir and rilpivirine. Injection dosing should be resumed on the day oral dosing completes.

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

If a patient plans to miss a scheduled injection visit by more than 7 days, take daily oral therapy to replace up to 2 consecutive monthly injection visits. The recommended oral daily dose is one 30-mg tablet of Vocabria (cabotegravir) and one 25-mg tablet of Edurant (rilpivirine). The first dose of oral therapy should be taken approximately 1 month after the last injection dose of Cabenuva and continued until the day injection dosing is restarted.

Cabenuva (cabotegravir/rilpivirine extended release injection) US Prescribing Information, ViiV Healthcare, January 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Desloratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nintedanib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nintedanib is primarily metabolised by esterases to the active metabolite BIBF 1202, with CYP3A4 contributing to a minor extent. BIBF 1202 is subsequently glucuronidated by UGTs 1A1, 1A7, 1A8 and 1A10. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glucose monohydrate (IV)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glucose is rapidly absorbed into cells and metabolized into carbon dioxide and water with the release of energy. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carfilzomib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolized, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYPs. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mobocertinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mobocertinib is mainly metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mitotane

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mitotane is primarily metabolized in adrenal cells. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lomustine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lomustine is extensively metabolised by CYPs, with animal studies suggesting involvement of CYP2C19, CYP2D6 and CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Perampanel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perampanel is metabolised mainly by CYP3A4/5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Perampanel is unlikely to have a clinically relevant effect on drugs metabolized by UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Larotrectinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Larotrectinib is mainly metabolized by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Larotrectinib is a weak inducer of UGTs in vitro but is unlikely to have a clinically significant effect on cabotegravir.

Description:

(See Summary)

Do Not Coadminister

Cabotegravir [oral] (CAB oral)

Ivosidenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ivosidenib is primarily metabolized by CYP3A4 and has the potential to induce UGTs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Based on a drug interaction study with rifampicin (another inducer of UGTs), coadministration may significantly reduce cabotegravir concentrations which may result in loss of therapeutic effect and development of resistance. Ivosidenib has a long half-life (approximately 2.4 to 5.4 days depending on indication), therefore a minimum of 2 weeks, but preferably 4 weeks, cessation period is recommended prior to initiation of cabotegravir due to the persisting inducing effect upon discontinuation of a strong inducer.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Secukinumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Secukinumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Phytomenadione (Vitamin K) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of phytomenadione is thought to involve CYP4F2 and glucuronidation. Renal elimination of phytomenadione is minimal. No effect is expected on cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Sarilumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sarilumab is an IL-6 receptor monoclonal antibody and likely undergoes elimination via binding to its target antigen. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nicotinamide (Niacinamide) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolized by xanthine oxidase and aldehyde oxidase. Renal elimination of unchanged nicotinamide is minimal.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tasimelteon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tasimelteon is extensively metabolised, mainly by CYP1A2 and CYP3A4 with a minor role for CYP2C9/2C19. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Tasimelteon is unlikely to inhibit or induce UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tixagevimab/ Cilgavimab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Tixagevimab and cilgavimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Tixagevimab and cilgavimab are not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Description:

(See Summary)

Potential Weak Interaction

Cabotegravir [oral] (CAB oral)

Cabotegravir PrEP [long acting] (CAB LA, PrEP)

Quality of Evidence: Very Low

Summary:

Oral cabotegravir may be used as an optional lead-in or if an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days. An optional oral lead-in with oral cabotegravir prior to the initiation of intramuscular cabotegravir may be used to assess the tolerability of cabotegravir. If an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, daily oral cabotegravir should be taken for up to 2 months to replace 1 missed scheduled every-2-month injection. The recommended oral daily dose is one 30-mg tablet of oral cabotegravir.

Description:

The healthcare provider and individual may decide to use an oral lead-in with oral cabotegravir prior to the initiation of Apretude to assess the tolerability of cabotegravir or the healthcare provider and individual may proceed directly to injection of Apretude without the use of an oral lead-in. No safety and efficacy data are available for use of Apretude without an oral lead-in. However, in HIV-1 treatment clinical trials, data show that an oral lead-in is not needed to ensure adequate plasma cabotegravir exposure upon initiation of injections and that the safety and efficacy results of Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) were similar when administered with and without an oral lead-in. If an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, take daily oral cabotegravir for a duration of up to 2 months to replace 1 missed scheduled every-2-month injection. The recommended oral daily dose is one 30-mg tablet of oral cabotegravir.

Apretude Prescribing Information, ViiV Healthcare, December 2021.

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trastuzumab emtansine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trastuzumab emtansine is a monoclonal antibody-drug conjugate. Trastuzumab does not undergo CYP mediated metabolism, whereas DM1 (an active component of emtansine) is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pyridoxine (Vitamin B6) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyridoxine is absorbed from the GI tract and is converted to the active form pyridoxal phosphate. It is excreted in the urine as 4-pyridoxic acid.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Midostaurin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midostaurin is metabolised mainly by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Lorlatinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorlatinib is primarily metabolised by CYP3A4 and UGT1A4 and, to a lesser extent, by CYP2C8, CYP2C19, CYP3A5 and UGT1A3. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Lorlatinib is a weak inducer of UGTs but no dose adjustment is required for medicinal products that are mainly metabolised by UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Molnupiravir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Molnupiravir is rapidly metabolized by esterases to a nucleoside metabolite which is phosphorylated to an active triphosphate. Molnupiravir is unlikely to have significant drug-drug interactions with other therapies.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Acalabrutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9. Acalabrutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Remdesivir

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Remdesivir does not affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cyclizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Retinol (Vitamin A) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bosutinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9. Bosutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tildrakizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tildrakizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isatuximab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isatuximab is a IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Epcoritamab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epcoritamab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Emicizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Emicizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Inclisiran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Inclisiran is primarily metabolised by nucleases and drug-drug interactions are not anticipated. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Inclisiran does not inhibit or induce CYPs or common drug transporters.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Relugolix

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Relugolix is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C8 and is a substrate of P-gp. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and has no inducing effects on CYPs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Glucosamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glucosamine has been reported to undergo metabolism in the liver, but the metabolic pathway remains unclear. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Glucosamine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Finerenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finerenone is metabolized mainly by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Finerenone is not expected to have a clinically relevant effect on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pitolisant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitolisant is primarily metabolised by CYP2D6 and to a lesser extent by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes. Pitolisant is unlikely to have a clinically significant effect on drugs metabolized by UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Calcitonin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolized via proteolysis in the kidney. Cabotegravir does not interfere with this pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Avelumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metamizole is a pro-drug that undergoes hydrolysis to 4-methylaminoantipyrine (MAA) which is then metabolised by CYPs 3A4, 2B6, 2C8 and 2C9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and has no inhibitory effect on CYPs. Metamizole is a moderate inducer of CYPs and could potentially induce UGT1A1 and UGT1A9. However, a drug interaction study with rifabutin, another moderate inducer, showed no clinically significant decrease in cabotegravir exposure.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Green tea extracts (Camellia sinensis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Green tea extracts weakly inhibit UGT1A1 in vitro and are unlikely to cause a clinically relevant interaction with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ginseng (Panax ginseng, Panax quinquefolis)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. In vitro studies suggest Asian ginseng (Panax ginseng) is unlikely to affect UGT1A1 or UGT1A9 at clinically relevant concentrations. No interaction is expected with American ginseng (Panax quinquefolius).

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ayahuasca

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. In vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, however, cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Isavuconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isavuconazole is metabolised by CYP3A4/5 and UGTs. Cabotegravir does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atomoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Donepezil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Cabotegravir does not interact with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Memantine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Memantine is eliminated by active renal secretion via OCT2 and MATE1. Cabotegravir does not interfere with this pathway.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dapoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapoxetine is metabolized by CYP2D6, CYP3A4 and flavin monooxygenase 1 whereas cabotegravir is mainly metabolized by UGT1A1. Cabotegravir has no inhibitory effects on CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bazedoxifene

Quality of Evidence: Very Low

Summary:

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Cabotegravir does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tibolone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with tibolone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tibolone is metabolized by several enzymatic pathways with no major involvement of CYP450. Cabotegravir does not interact with these metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Progesterone (HRT)

Quality of Evidence: Very Low

Summary:

Coadministration with progesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Progesterone is metabolized by CYP3A4. Cabotegravir does not inhibit or induce drug metabolizing enzymes. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Silodosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Silodosin is metabolized by CYP3A4, UGT2B7, as well as alcohol and aldehyde dehydrogenase. Cabotegravir does not interfere with these pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dapivirine (DPV, PrEP)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Polatuzumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Polatuzumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with cabotegravir. MMAE is a substrate of CYP3A4 and P-gp, but no interaction is expected as cabotegravir has no inhibitory or inducing effects on CYPs and polatuzumab vedotin has no inhibitory or inducing effects on UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ramelteon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramelteon is mainly metabolized by CYP1A2, with CYP3A4 and CYP2C9/2C19 having a minor role. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Ramelteon is unlikely to inhibit or induce UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Carbocisteine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbocisteine is metabolized in the liver via acetylation, decarboxylation and sulfoxidation with up to 60% excreted unchanged in the urine. The likelihood of a clinically significant drug interaction is low and no studies have been performed. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Biotin (Vitamin B7, Vitamin H) [in multivitamins]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas. A pharmacokinetic interaction is unlikely with biotin alone. However, biotin can be found in multivitamin preparations containing polyvalent cations. Cabotegravir, similarly to other integrase inhibitors, chelates with polyvalent cations resulting in a reduced absorption of cabotegravir. Multivitamin preparations containing polyvalent cations should be administered at least 2 hours before or 4 hours after taking oral cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Blinatumomab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tisotumab vedotin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tisotumab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with cabotegravir. MMAE is a substrate of CYP3A4 and P-gp but no interaction is expected as cabotegravir does not inhibit or induce CYPs and tisotumab vedotin does not inhibit or induce CYP3A4 or UGT1A1.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Psilocybin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Psilocybin is rapidly dephosphorylated to psilocin which is responsible for the hallucinogenic effects. Psilocin is deactivated to multiple metabolites by alcohol dehydrogenase and monoamine oxidase or glucuronidated to psilocin-O-glucuronide by UGT1A9 in the liver or UGT1A10 in the small intestine before excretion in the urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect psilocybin or psilocin metabolism. Psilocybin and psilocin are unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Ixekizumab

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ixekizumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trastuzumab

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Telotristat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telotristat ethyl undergoes hydrolysis via carboxylesterases to the major active metabolite telotristat. Metabolism of telotristat is unlikely to be CYP mediated. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect telotristat metabolism. Telotristat is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cabergoline (Parkinson's disease)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cabazitaxel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9, however, cabazitaxel has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cabergoline (lactation suppression)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Teicoplanin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Teicoplanin is primarily excreted via urine as unchanged drug. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Safinamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Safinamide is metabolised by high-capacity amidases which are yet to be fully characterised, CYP enzymes are unlikely to be involved. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect safinamide metabolism. Safinamide is unlikely to inhibit or induce UGT1A1 or UGT1A9 at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Moclobemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moclobemide is metabolised via multiple pathways, including in part by CYP2C19 and CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect moclobemide metabolism. Moclobemide is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nitazenes

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitazenes are a family of synthetic opioids with a potency several hundred times stronger than morphine. Little is known about nitazene metabolism but it is likely to involve CYP metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Biotin (Vitamin B7, Vitamin H) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tenapanor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenapanor is minimally absorbed following oral administration and is eliminated mainly unchanged in the faeces. Limited metabolism to M1, an inactive metabolite, occurs by primarily by CYP3A4/5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Phentermine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phentermine is not extensively metabolised with 70-80% of an oral dose eliminated primarily unchanged in urine. In vitro studies indicate that CYP3A4 is the primary enzyme responsible for the limited metabolism of phentermine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Abemaciclib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolized by CYP3A4. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Cabotegravir is metabolized by UGT1A1 and to a lesser extent UGT1A9. Abemaciclib has no inhibitory or inducing effects on drug metabolizing enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Tepotinib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tepotinib is metabolized by CYP3A4 and CYP2C8. No single metabolic pathway accounted for more than 25% of tepotinib elimination. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Tepotinib is unlikely to have a clinically significant effect on UGTs. Cabotegravir does not inhibit or induce CYP3A4 or CYP2C8.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cefuroxime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cariprazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cariprazine is unlikely to affect UGTs. Cabotegravir does not inhibit or induce CYP3A4 or CYP2D6.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Eletriptan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eletriptan is metabolised by CYP3A4 and does not induce or inhibit CYPs. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Abatacept

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Alogliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pseudoephedrine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pseudoephedrine is minimally metabolised by N-demethylation and ~70% is excreted unchanged in the urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect pseudoephedrine elimination. Pseudoephedrine is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Cyanocobalamin (Vitamin B12) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Colecalciferol (Vitamin D3) [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for an interaction with cabotegravir.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Linaclotide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linaclotide is metabolised locally within the gastrointestinal tract and extensive studies have shown no CYP or transporter interactions occur. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Guanfacine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Guanfacine is metabolised by CYP3A4/5. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP3A4/5. Guanfacine is unlikely to inhibit or induce UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Riluzole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Riluzole is mainly metabolized by CYP1A2 and the major active metabolite is then glucuronidated. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dextromethorphan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYP2D6. Dextromethorphan is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mitomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mitomycin is hepatically metabolised but the enzymes involved are unclear; modulation of CYP450 is unlikely to be significant. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect mitomycin metabolism. Mitomycin is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brinzolamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs. Brinzolamide is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Minocycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Minocycline is almost completely absorbed with one third excreted as unchanged drug. Unlike other tetracyclines, there is evidence that partial metabolism by CYPs (including CYP3A4) occurs. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir is unlikely to affect minocycline concentrations. Minocycline is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Dexketoprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Cabotegravir does not inhibit or induce CYPs/UGTs. Dexketoprofen is unlikely to affect UGTs.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Bromocriptine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Bromocriptine is unlikely to affect UGTs. Cabotegravir does not inhibit or induce CYP3A4.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Triamterene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamterene is mainly metabolized by CYP1A2. Cabotegravir does not inhibit or induce CYP1A2.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Febuxostat

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Febuxostat is extensively metabolized by multiple UGT enzymes (UGTs 1A1, 1A3, 1A8, 1A9 and 2B7) and CYP enzymes (CYPs 1A1, 1A2, 2C8 and 2C9). Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP or UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Atogepant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atogepant is metabolized primarily by CYP3A4 and is a substrate of OATP. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Atogepant is not expected to have a clinically relevant effect on drugs metabolized by UGT enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Iodine [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iodine is converted to iodide, which is trapped in the thyroid gland. Iodides are excreted mainly in the urine with smaller amounts excreted in the faeces, sweat and saliva.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Filgrastim

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Filgrastim is eliminated mainly by neutrophil-mediated clearance and renal excretion.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Nefopam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nefopam undergoes extensive hepatic metabolism and both unchanged nefopam and metabolites are excreted principally in the urine. Limited data suggest that CYP and UGT enzymes may have a role in the metabolism of nefopam. Cabotegravir is mainly metabolised by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Brexpiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9 and does not inhibit or induce CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Trenbolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trenbolone is mainly excreted in urine as glucuronide conjugates. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Trenbolone is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Oxymetholone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxymetholone undergoes oxidation, reduction and hydroxylation; CYP enzymes are unlikely to be involved. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Oxymetholone is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Collagen hydrolysate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Collagen hydrolysate is unlikely to affect UGT1A1 or UGT1A9.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Chlormadinone (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Cabotegravir does not inhibit or induce P450 enzymes. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol/levonorgestrel (0.03/0.15 mg) did not significantly affect ethinylestradiol and levonorgestrel concentrations. Similarly, cabotegravir is unlikely to alter chlormadinone concentrations.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Abiraterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Cabotegravir does not interact with these metabolic pathways.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Mucuna pruriens

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on very limited data for metabolism and clearance, a clinically significant interaction is unlikely. No pharmacokinetic interactions have been reported with Mucuna pruriens.

Description:

(See Summary)

Potential Interaction

Cabotegravir [oral] (CAB oral)

Enteral Feeds

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Enteral feeds contain polyvalent cations. Cabotegravir concentrations may decrease due to chelation with polyvalent cations. Where possible, a break in enteral feeding is advised for 2 hours before and 4 hours after taking oral cabotegravir.

Description:

(See Summary)