Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug.

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. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied. Abemaciclib is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase abemaciclib concentrations. A modelling study predicted that moderate CYP3A4 inhibitors (i.e., diltiazem and verapamil) increased the AUC of abemaciclib’s potency adjusted unbound active species C by 1.6- to 2.4-fold. A similar effect may occur with lenacapavir. No a priori dose adjustment of abemaciclib is needed, however, monitor closely for signs of toxicity. Monitor abemaciclib concentrations, if available. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Abemaciclib is a fairly sensitive CYP3A4 substrate, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase abiraterone exposure, however, to an extent that is not clinically relevant. When coadministered with the strong CYP3A4 inhibitor, ketoconazole, abiraterone AUC increased only by 15%.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 but a clinically significant effect on abrocitinib is not expected as CYP3A4 is a minor route of metabolism. Abrocitinib is not expected to have a clinically relevant effect on CYP3A4 or UGTs.

Coadministration has not been studied. Acalabrutinib is metabolised by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase acalabrutinib exposure. PBPK simulations with acalabrutinib and moderate CYP3A4 inhibitors increased acalabrutinib Cmax and AUC approximately 2- to 3-fold. The European product label for acalabrutinib recommends no dose adjustment with moderate CYP3A4 inhibitors, however, the American product label recommends to reduce the dose of acalabrutinib from 100 mg twice daily to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Abemaciclib is a sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (renal transporter unknown, possibly OATs or OCTs). Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C9, CYP1A2 and CYP2C19 in the range of clinically relevant concentrations.

Coadministration has not been studied. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. In vitro studies have shown acetazolamide may competitively inhibit renal transporters OAT1, OAT3 and OAT4. Inhibition of these renal transporters is unlikely to lead alter lenacapavir concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but, based on metabolism and clearance, a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation. Lenacapavir does not inhibit or induce UGT enzymes in the range of clinically significant concentrations.

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

Coadministration has not been studied. 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 lenacapavir should be separated by 4 hours. [Note: this interaction is not specific for lenacapavir, but for any oral medication taken with activated charcoal.] No interaction is expected when lenacapavir is administered subcutaneously.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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).

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 CYP3A4 or UGT1A1. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 but is not expected to affect afatinib as afatinib does not undergo CYP3A4-mediated metabolism.

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. The clinical relevance of the inducing effect of African potato is unknown as lenacapavir is a moderate inhibitor of CYP3A4 and may partly compensate the inducing effect. Coadministration of African potato and lopinavir/ritonavir did not result in significant pharmacokinetic changes.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP1A2 in the range of clinically significant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to have a significant effect on albendazole.

Coadministration has not been studied but based on metabolism and clearance, as well as limited drug-drug interaction data, a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids.

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4, however, no clinically relevant effect is expected on lenacapavir exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcuronium is predominantly eliminated unchanged via the kidneys. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Alectinib does not inhibit or induce CYP3A4 to a clinically relevant extent. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 but it is not expected to significantly increase alectinib exposure.

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. Lenacapavir is mainly cleared as unchanged drug. 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.

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

Coadministration has not been studied. Alfentanil undergoes extensive CYP3A4 metabolism and is a sensitive CYP3A4 substrate. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% and has the potential to increase alfentanil concentrations. Administer with caution due to the potential risk of prolonged or delayed respiratory depression. A dose adjustment of alfentanil may be required. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These concentrations may affect the exposure of the sensitive CYP3A4 substrate alfentanil even if it is initiated within 9 months after the last subcutaneous dose of lenacapavir.

Coadministration has not been studied. Alfuzosin is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase alfuzosin concentrations which may lead to severe hypotension. Use with caution. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Alfuzosin is a sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. P-glycoprotein is a major determinant of aliskiren bioavailability. Significant interactions are not expected with lenacapavir as it is a weak inhibitor of P-gp.

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.

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. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to cause a significant interaction as CYP3A4 plays a minor role in almotriptan elimination.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Aloe vera is only a weak inhibitor of CYPs in vitro and is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Alogliptin was shown to have no inhibitory or inducing effect on CYPs at concentrations achieved with the recommended dose of 25 mg alogliptin. In addition, alogliptin was shown to be neither a substrate nor an inhibitor of the renal transporters OAT1, OAT3 or OCT2 and to cause no interactions with P-glycoprotein substrates.

Coadministration has not been studied. In vitro data indicate that alosetron is metabolized by CYPs 2C9 (30%), 3A4 (18%) and 1A2 (10%); however, in vivo data suggest that CYP1A2 plays a more prominent role. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C9 or CYP1A2 in the range of clinically significant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4, however, a clinically significant interaction is unlikely given the multiple elimination pathways and that CYP3A4 is not the major cytochrome involved in the metabolism of alosetron.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase alpelisib concentrations. However, no clinically significant effect is expected as CYP3A4 represents a minor pathway in alpelisib metabolism. A PBPK model predicted coadministration of a strong CYP3A4 inhibitor (ritonavir, 100 mg twice daily) to increase alpelisib AUC by 1.16-fold. No dose adjustment of alpelisib is necessary and standard dosing can be continued.

Coadministration has not been studied. Alprazolam is mainly metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase alprazolam exposure. Fluvoxamine (another moderate inhibitor of CYP3A4) increased alprazolam exposure by almost 2-fold and clearance was halved. The increased alprazolam concentrations resulted in decreased psychomotor performance and memory. If alprazolam is coadministered with lenacapavir, the initial alprazolam dosage should be halved and titration to the lowest effective dose is recommended. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These concentrations may affect the exposure of alprazolam if it is initiated within 9 months after the last dose of subcutaneous dose of lenacapavir. Alprazolam is a fairly sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Alprostadil is unlikely to affect CYP or UGT enzymes.

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 via OCT2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4, however, no clinically significant effect on ambrisentan is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged by the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on CYP1A2 in the range of clinically relevant concentrations.

Coadministration has not been studied but is not recommended. Amiodarone is metabolized by CYPs 3A4 and 2C8. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% and has the potential to increase amiodarone concentrations. The product label for amiodarone recommends to avoid coadministration with CYP3A4 inhibitors. Amiodarone is a P-gp inhibitor and could potentially increase lenacapavir concentrations although to an extent that is not considered to be clinically relevant. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Amiodarone is not a sensitive CYP3A4 substrate but is a narrow therapeutic index drug therefore use with caution if coadministration is necessary.

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). Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 or CYP2C19 in the range of clinically significant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4. Amlodipine is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase amlodipine exposure. Diltiazem (a moderate CYP3A4 inhibitor) increased amlodipine exposure by 60%. A comparable increase is expected with lenacapavir. Clinical monitoring is advised with dose adjustment if needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amodiaquine is metabolized mainly by CYP2C8. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP12C8 in the range of clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

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

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and tubular secretion. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on lenacapavir is expected and no a priori dose adjustment is required.

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 via UGT1A4 to metabolites that are pharmacologically inactive. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase anastrozole exposure. The clinical significance is unknown. Monitor for anastrozole toxicity.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Absorption of lenacapavir is unlikely to be influenced by changes in gastric pH.

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

Coadministration has not been studied but is not recommended. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Apalutamide also induces UGT1A1. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Coadministration with rifampicin (a strong inducer) decreased lenacapavir exposure by 85%. Coadministration with apalutamide may impair the efficacy of lenacapavir and lead to the 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 lenacapavir due to the persisting inducing effect upon discontinuation of a strong inducer.

Coadministration has not been studied. Apixaban is a substrate of P-gp and is metabolized by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir is a weak inhibitor of P-gp and a moderate inhibitor of CYP3A4 and may increase apixaban exposure. Apixaban exposure increased by 40% in presence of diltiazem (a moderate CYP3A4 inhibitor) and a similar interaction may occur with lenacapavir. The product label for apixaban indicates that no dose adjustment is required for apixaban when coadministered with drugs that are not strong inhibitors of CYP3A4. However, monitoring for increased apixaban side effects is still recommended.

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

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. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Coadministration of apremilast with ketoconazole (a strong CYP3A4 inhibitor) increased apremilast AUC by 36%. This effect is not considered to be clinically significant and does not warrant a dose adjustment of apremilast. Similarly, lenacapavir is unlikely to significantly alter apremilast exposure. Furthermore, apremilast has no inhibitory or inducing effects on CYPs 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 oral lenacapavir.

Coadministration has not been studied. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and could potentially increase aprepitant concentrations. The European product label for aprepitant advises caution with CYP3A4 inhibitors, whereas the American product label advises to avoid concomitant use of aprepitant and moderate to strong CYP3A4 inhibitors. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect on CYP3A4 and UGT on day 8 which is clinically insignificant by two weeks. Any transient change in lenacapavir exposure is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Lenacapavir is a moderate CYP3A4 inhibitor, however, erythromycin (a strong CYP3A4 inhibitor) had no effect on argatroban pharmacokinetics and pharmacodynamics and a pharmacokinetic interaction with lenacapavir is unlikely.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase aripiprazole exposure, although to a limited extent and no a priori dosage adjustment is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Arsenic trioxide is hydrolysed to arsenious acid (the pharmacologically active metabolite) which is then methylated to less cytotoxic metabolites primarily in the liver (non-CYP mediated). Arsenious acid is also oxidated to arsenic acid, which may occur in numerous tissues via enzymatic or nonenzymatic processes. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is unlikely to affect arsenic trioxide metabolism. Arsenic trioxide does not inhibit or induce CYP3A4 and is unlikely to affect UGT1A1.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolism via UGTs 1A9 and 2B7. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs, CYP2A6 or CYP2B6 in the range of clinical concentrations. Lenacapavir is a substrate and a moderate inhibitor of CYP3A4 and could increase artemisinin exposure but this is unlikely to be clinically relevant. Artemisinins induce CYP3A4 and/or CYP2C19 and may decrease lenacapavir concentrations. However, this is unlikely to clinically relevant due to the short treatment duration of artemisinins.

Coadministration has not been studied. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase asciminib exposure, although to a limited extent. Coadministration of asciminib (40 mg single dose) with clarithromycin (a strong CYP3A4 inhibitor) increased asciminib AUC and Cmax by 36% and 19%, although no clinically significant effect on asciminib concentrations was observed when coadministered with itraconazole, which is also a strong CYP3A4 inhibitor.

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. Lenacapavir does not interfere with this metabolic pathway.

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. A pharmacokinetic interaction is unlikely with vitamin C itself, or with the associated multivitamins.

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, CYP2D6 (minor)). Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs or CYP1A2 or CYP2D6 in the range of clinically relevant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4, however, a clinically significant interaction is unlikely as CYP3A4 plays a minor role in asenapine metabolism.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Ashwagandha extracts had no effect on CYP enzymes in vitro.

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. Less than 0.1% of a total injected dose is recovered in urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Lenacapavir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Lenacapavir does not interfere with this metabolic pathway.

Coadministration has not been studied and is not recommended due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Astemizole is a substrate of CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and increased exposure of the midazolam (a sensitive CYP3A4 substrate) by 259-308% (after a loading dose of lenacapavir of 600 mg twice daily for 2 days) and could increase astemizole exposure and the related risk of serious adverse events. If lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These concentrations may affect the exposure of astemizole even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

Coadministration has not been studied but is not recommended. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with atazanavir/cobicistat (a strong CYP3A4, UGT1A1 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 320% by 560%. A similar increase is expected with atazanavir/ritonavir and therefore coadministration is not recommended due to the risk of adverse effects.

Coadministration has not been studied but is not recommended. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with atazanavir/cobicistat (a strong CYP3A4, UGT1A1 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 320% by 560%. A similar increase is expected with atazanavir alone and therefore coadministration is not recommended due to the risk of adverse effects.

Coadministration is not recommended due to the risk of adverse effects. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of oral lenacapavir with atazanavir/cobicistat (a strong CYP3A4, UGT1A1 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 321% and 560%.

Coadministration has not been studied. Atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory effects on OCT2 and MATE1 in the range of clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Atogepant is not expected to have a clinically relevant effect on drugs metabolized by CYP or UGT enzymes. Lenacapavir is a moderate inhibitor of CYP3A4. PBPK modeling suggested a 1.7-fold increase in atogepant AUC with moderate CYP3A4 inhibitors. This is not expected to be clinically significant and no dosage adjustment is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

Coadministration has not been studied. Atorvastatin is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and has the potential to increase exposure of atorvastatin, although to a limited extent as atorvastatin is not a sensitive CYP3A4 substrate. No a priori dose adjustment of atorvastatin is required.

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

Coadministration has not been studied. Based on metabolism/elimination profiles of both drugs, there is little potential for interaction 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 little potential for clinically significant interactions with lenacapavir via modulation of, or competition for metabolic pathways.

Coadministration has not been studied. Avanafil is primarily metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase avanafil exposure. Coadministration with erythromycin (a moderate inhibitor) increased avanafil exposure by 3-fold and prolonged the half-life of avanafil by approximately 8 hours. Lenacapavir is expected to have similar effect. The product label for avanafil recommends a maximum dose of 100 mg, not to exceed once every 48 hours for individuals taking concomitant moderate inhibitors such as lenacapavir. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Avanafil is a sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied and should be avoided. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Lenacapavir is a moderate inhibitor of CYP3A4 and could significantly increase avapritinib exposure. Coadministration with fluconazole (a moderate CYP3A4 inhibitor) is predicted to increase avapritinib exposure by 210% after multiple doses and a similar increase may occur with lenacapavir. Coadministration should be avoided. If the concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dose of avapritinib should be reduced from 300 mg to 100 mg orally once daily for patients with GIST, and from 200 mg to 50 mg orally once daily for patients with advanced systematic mastocytosis. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Avapritinib is a sensitive CYP3A4 substrate, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Avatrombopag does not inhibit or induce CYP3A. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase concentrations of avatrombopag. Coadministration of avatrombopag and itraconazole (a strong CYP3A4 inhibitor) increased avatrombopag exposure by 37%. No a priori dose adjustment is needed for avatrombopag but monitor platelet counts and adjust the avatrombopag dose as necessary as indicated in the avatrombopag product label.

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.

Coadministration has not been studied. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Axitinib does not inhibit or induce CYP3A4 or UGTs .Lenacapavir is a moderate inhibitor of CYP3A4 and could increase axitinib exposure. The clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended for axitinib. Close monitoring for axitinib toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Although in vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, this is unlikely to cause a clinically significant increase in lenacapavir exposure.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Azacitidine does not inhibit or induce CYP enzymes.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azilsartan is metabolized mainly by CYP2C9. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C9 in the range of clinical concentrations.

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-gp and MRP2. Lenacapavir is mainly cleared as unchanged drug and is a weak inhibitor of P-gp and therefore is unlikely to cause a clinically significant interaction.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP or UGT enzymes. Lenacapavir does not inhibit the renal transporters MATE, OATs, BCRP in the range of clinically relevant concentrations and is only a weak inhibitor of P-gp. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to have a significant impact on baricitinib exposure.

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

Coadministration 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. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and therefore could potentially increase bazedoxifene, however this increase is unlikely to be clinically significant.

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. This active metabolite is subsequently converted to inactive metabolites via CYP3A4/5. Coadministration with the strong CYP3A4 inhibitor darunavir/ritonavir (600/100 mg twice daily) and inhaled beclometasone diproprionate (160 mg twice daily) decreased the AUC and Cmax of the active metabolite by 11% and 19%, respectively. No significant effect on adrenal function was seen. Similarly, no adverse effects are expected with lenacapavir, a moderate CYP3A4 inhibitor.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% (after a loading dose of lenacapavir of 600 mg twice daily for 2 days) and has the potential to increase bedaquiline concentrations. The combination of bedaquiline and moderate or strong CYP3A4 inhibitors used systemically for more than 14 consecutive days should be avoided. If coadministration is necessary, clinical monitoring including frequent ECG assessment and monitoring of transaminases is recommended.

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

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

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Bempedoic acid does not inhibit or induce CYP3A4 and UGTs.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not inhibit or induce CYP1A2 in the range of clinically relevant concentrations. Bendamustine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

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

Coadministration has not been studied. Bepridil is metabolized by CYPs 2D6 (major) and 3A4. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations. However, lenacapavir is a moderate inhibitor of CYP3A4 and therefore has the potential to increase bepridil concentrations, although to a limited extent. Use with caution due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Beta-alanine is unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

Coadministration has not been studied and is not recommended. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Betamethasone is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and has the potential to increase exposure of betamethasone and the related risk of Cushing’s syndrome and adrenal suppression. Betamethasone is a moderate inducer of CYP3A4 and could potentially decrease lenacapavir concentrations. A reduction in lenacapavir concentrations may result in loss of therapeutic effect and development of resistance and therefore coadministration is not recommended. At least a 2-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a moderate inducer. Note, the inducing effect is expected to be modest when using lower doses of betamethasone and low dose betamethasone is unlikely to have a clinically significant effect on lenacapavir.

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).

Coadministration has not been studied. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Lenacapavir is mainly cleared as unchanged drug and is a weak inhibitor of P-gp. Lenacapavir is not considered to be a meaningful inhibitor of P-gp therefore no a priori dose adjustment of betrixaban is needed. However, monitoring for increased betrixaban side effects is still recommended.

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

Coadministration has not been studied and is not recommended. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300 mg/m2/day). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with efavirenz (a moderate CYP3A4 and UGT inducer) decreased lenacapavir AUC and Cmax by 56% and 36%. Thus, coadministration with bexarotene is not recommended as it may impair lenacapavir efficacy. In addition, lenacapavir could potentially increase bexarotene exposure and the related adverse effects.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Bicalutamide is a weak inhibitor of CYP3A4 and inhibited UGT1A9 in vitro but is unlikely to have a clinically significant effect on lenacapavir. Lenacapavir is a moderate inhibitor of CYP3A4 but no clinically significant interaction is expected with bicalutamide as CYP3A4 contributes only partly to its metabolism.

Coadministration with Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bictegravir is metabolised by CYP3A4 and UGT1A1; emtricitabine and tenofovir alafenamide are eliminated renally. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase bictegravir, although to an extent that is not considered to be clinically relevant. No a priori dose adjustment is needed.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Bilastine is unlikely to affect CYP3A4 or UGT1A1.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not inhibit or induce the enzymes involved in binimetinib metabolism. Binimetinib is unlikely to affect CYP3A4.

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.

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.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Bismuth subsalicylate is unlikely to affect lenacapavir elimination or metabolism.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on CYP2D6. However, lenacapavir is a moderate inhibitor of CYP3A4 and could increase bisoprolol concentrations although to a limited extent. No a priori dose adjustment is needed.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. No effect on lenacapavir is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate) and in vitro studies suggest black cohosh is unlikely to affect UGT1A1 at clinically relevant concentrations.

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

Coadministration has not been studied but based on metabolism and clearance a 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.

Coadministration has not been studied. Bortezomib is mainly metabolized by CYPs 3A4 and 2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase bortezomib concentrations. Coadministration of ketoconazole (a strong CYP3A4 inhibitor) increased bortezomib AUC by 35%. Lenacapavir may not cause a significant increase in bortezomib exposure, however monitoring for bortezomib-related side effects is still recommended given the narrow therapeutic index of bortezomib. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Bortezomib is not a sensitive CYP3A4 substrate but is a narrow therapeutic index drug, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied and is not recommended. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Bosentan is a substrate and moderate inducer of CYP3A4 and is expected to decrease lenacapavir exposure. Coadministration of the moderate CYP3A4 inducer efavirenz (600 mg once daily) and lenacapavir (300 mg single oral dose) decreased lenacapavir AUC and Cmax by 56% and 36%. A similar effect may occur with bosentan and therefore coadministration is not recommended as it may result in loss of therapeutic effect and development of resistance. At least a 2-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a moderate inducer.

Coadministration has not been studied and is not recommended. Bosutinib is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase bosutinib concentrations. Coadministration of bosutinib (100 mg single dose) and ketoconazole (a strong CYP3A4 inhibitor) increased bosutinib AUC by 9-fold. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Bosutinib is a sensitive CYP3A4 substrate, therefore caution is still needed in the initial months after stopping lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. BCAAs are unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied. 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 lenacapavir. MMAE is a substrate of CYP3A4 and P-gp. Lenacapavir is a moderate inhibitor of CYP3A4 and a weak inhibitor of P-gp and therefore could potentially increase MMAE exposure, although to a limited extent. No a priori dose adjustment is needed but monitoring for adverse effects is recommended. If neutropenia develops, refer to the dosing recommendations for neutropenia in the product label for brentuximab vedotin.

Coadministration has not been studied. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase brexpiprazole concentrations. No a priori dose adjustment of brexpiprazole is recommended for extensive CYP2D6 metabolisers, but monitor for toxicity, such as confusion, restlessness and sedation. A dosing modification to a quarter of the recommended dose is required for known CYP2D6 poor metabolisers while taking moderate CYP3A4 inhibitors.

Coadministration has not been studied. Brigatinib is metabolised by CYP2C8 and CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase concentrations of brigatinib. A PBPK modelling study predicted moderate CYP3A inhibitors (e.g., diltiazem and verapamil) may increase brigatinib AUC by approximately 40%. The European product label for brigatinib states that no dose adjustment is required with moderate CYP3A inhibitors, but patients should be closely monitored. However, the American product label for brigatinib suggests a brigatinib dose reduction of ~40% with moderate CYP3A inhibitors.

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

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. Brincidofovir is a substrate of OATP1B1. Lenacapavir is mainly cleared as unchanged drug and does not inhibit these transporters.

Coadministration has not been studied. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Brinzolamide does not inhibit or induce CYP3A4. However, lenacapavir is a moderate CYP3A4 inhibitor and may increase brinzolamide concentrations. Caution is advised, and a dose reduction could be considered at higher doses. Monitor for increased side effects such as blurred vision or eye irritation and consider intraocular pressure checks during the first week of coadministration. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir, therefore caution is still needed in the months after stopping lenacapavir.

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 play a role. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on CYP2D6 and CYP1A2. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to significantly alter bromazepam exposure.

Coadministration has not been studied. Bromocriptine is metabolised by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Bromocriptine is unlikely to affect CYP3A4 or UGT1A1. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase concentrations of bromocriptine. Monitor patients for toxicity and consider a bromocriptine dose decrease if necessary. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir, therefore caution is still needed in the months after stopping lenacapavir.

Coadministration has not been studied. Budesonide is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and has the potential to increase exposure of budesonide and may consequently increase the risk for Cushing’s syndrome and adrenal suppression. It is recommended to initiate with the lowest starting dose and titrate carefully while monitoring for safety.

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). Lenacapavir does not interfere with this elimination pathway.

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%). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

Coadministration has not been studied. Bupivacaine is predominantly metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. A clinical interaction study with bupivacaine and itraconazole (a strong CYP3A4 inhibitor), reported a 20-25% increase in steady state concentration of bupivacaine when administered with itraconazole, compared to placebo. Based on these data, lenacapavir is not expected to cause a significant increase in bupivacaine exposure.

Coadministration has not been studied. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Lenacapavir is mainly cleared as unchanged drug. Lenacapavir does not inhibit or induce UGTs in the range of clinically significant concentrations but is a moderate inhibitor of CYP3A4 and could increase buprenorphine concentrations although to a limited extent. Based on drug interaction data with the strong CYP3A4 inhibitor ritonavir, the increase in buprenorphine exposure with lenacapavir is not expected to cause significant pharmacodynamic changes in a population of opioid tolerant patients. Thus, an a priori dose adjustment of buprenorphine is not necessary, but should be guided by clinical monitoring.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2B6 in the range of clinically significant concentrations.

Coadministration has not been studied. Buspirone is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase buspirone exposure. Fluvoxamine (another moderate inhibitor of CYP3A4) increased buspirone (10 mg single dose) Cmax by 2-fold and AUC by 2.4-fold and decreased the production of the active 1-PP metabolite of buspirone (n=10). A similar effect is expected with lenacapavir. A low dose of buspirone used cautiously is recommended with dose adjustment based on the clinical response. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Buspirone is a sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Busulfan is unlikely to affect lenacapavir elimination. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase busulfan concentrations. Itraconazole (a strong CYP3A4 inhibitor) decreased busulfan clearance by approximately 20% which may increase the risk and severity of myelosuppression. Patients should be monitored for signs of toxicity. Note; if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Busulfan is not a sensitive CYP3A4 substrate but is a narrow therapeutic index drug, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Cabazitaxel is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could increase cabazitaxel concentrations although to a limited extent. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) increased cabazitaxel exposure by 25%. A less pronounced effect is expected with lenacapavir given that it is a moderate inhibitor. No a priori dose adjustment is needed.

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.

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.

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.

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.

Coadministration has not been studied. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Rilpivirine is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and could potentially increase rilpivirine, although to an extent that is not considered to be clinically relevant. No a priori dose adjustment is needed.

Coadministration has not been studied. Cabozantinib is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could increase cabozantinib concentrations. Ketoconazole (a strong CYP3A4 inhibitor) increased cabozantinib AUC by 38%. The clinical relevance of this interaction is unknown. No a priori dose adjustment is needed for cabozantinib, however, close monitoring for cabozantinib tolerability is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not affect CYP1A2. Caffeine is unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP1A2 in the range of clinically relevant concentrations.

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. Lenacapavir does not interfere with this pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Calcium is eliminated through faeces, urine and sweat.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically significant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on lenacapavir is expected and no a priori dose adjustment is required.

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

Coadministration has not been studied. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase cannabidiol concentrations due to CYP3A4 inhibition, although to a limited extent. Monitoring for adverse effects is recommended.

Coadministration has not been studied. Tetrahydrocannabinol (THC, the psychoactive component of cannabis) is metabolised mainly by CYP2C9 and to a lesser extent by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase concentrations of THC, although to a limited extent. The patient should be made aware of potential increased side effects.

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. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Lenacapavir does not interfere with these metabolic pathways.

Coadministration has not been studied. Capmatinib is primarily metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase capmatinib exposure, although to a limited extent. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered.

Coadministration has not been studied. Capreomycin is predominantly excreted via the kidneys as unchanged drug, partly by glomerular filtration and partly by tubular secretion. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied and is contraindicated. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Coadministration of the strong inducer rifampicin (600 mg once daily) and lenacapavir (300 mg single oral dose) decreased lenacapavir AUC and Cmax by 84% and 55%. Similarly, the strong inducer carbamazepine could substantially reduce lenacapavir concentrations which may result in loss of therapeutic effect and development of resistance. At least a 4-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a strong inducer.

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

Coadministration has not been studied but 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.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

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. Lenacapavir is mainly cleared as unchanged drug.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to have a clinically relevant effect on carfilzomib concentrations as CYP3A4 only represents a minor metabolic pathway. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs or UGT1A1.

Coadministration has not been studied and is not recommended. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Cariprazine is unlikely to affect CYP3A4 or UGT1A1. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase concentrations of cariprazine. Cariprazine and its metabolites have very long elimination half-lives and changes in dose may not be fully reflected in plasma for several weeks. The European product label for cariprazine (but not the American product label) contraindicates coadministration with moderate CYP3A4 inhibitors. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir, therefore caution is still needed in the months after stopping lenacapavir.

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 metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on the enzymes involved in carvedilol metabolism.

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.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Cat’s claw is a strong inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Cat’s claw could increase lenacapavir concentrations, however, this is unlikely to be clinically significant. Coadministration of the strong CYP3A4 inhibitor voriconazole (200 and 400 mg twice daily) with lenacapavir (300 mg oral dose) increased lenacapavir AUC and Cmax by 41% and 9%. These changes are not considered to be clinically relevant.

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). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Cedazuridine does not inhibit or induce CYP enzymes.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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

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 OAT3 participates in the renal elimination of cefotaxime. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolized by CYP2C9. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C9 in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

Coadministration has not been studied and is not recommended. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater could potentially decrease lenacapavir concentrations. A reduction in lenacapavir concentrations may result in loss of therapeutic effect and development of resistance and therefore coadministration is not recommended. At least a 2-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Ceritinib is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of lenacapavir with darunavir/cobicistat (another strong CYP3A4 inhibitor) increased lenacapavir exposure by 2.1 fold. This increase is not considered to be clinically relevant and does not warrant a dose adjustment. Ceritinib may cause a similar increase in lenacapavir exposure.

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. Lenacapavir is mainly cleared as unchanged drug.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolised via UGTs, in particular UGT2B7. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically relevant concentrations. In vitro studies have shown that chloramphenicol can inhibit CYP3A4 but this is unlikely to cause a clinically significant interaction as lenacapavir is a non-sensitive substrate of CYP3A4. Coadministration with voriconazole (a strong CYP3A4 inhibitor) increased lenacapavir exposure by 30%. This increase is not considered to be clinically relevant.

Coadministration has not been studied. Chlordiazepoxide is extensively metabolized by hepatic microsomal enzymes. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase chlordiazepoxide exposure. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of chlordiazepoxide even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase chlormadinone exposure, although to an extent that does not require dose adjustment.

Coadministration has not been studied. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C8, CYP2D6 in the range of clinical concentrations. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to significantly increase chloroquine exposure due to the multiple elimination pathways. Chloroquine inhibits P-gp and could increase lenacapavir (substrate of P-gp), but to an extent that is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP1A2 or CYP2D6 in the range of clinically relevant concentrations

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

Coadministration has not been studied. Ciclesonide can be administered with lenacapavir, a moderate inhibitor of CYP3A4, without dose adjustment, but with close monitoring. There is a risk of steroid side effects occurring, particularly if a high dose is used, or in case of prolonged administration, or if used with another medicine containing corticosteroids. These side effects are also more likely during periods of physiological stress. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Coadministration of the strong CYP3A4 inhibitor ketoconazole (400 mg daily for 7 days) with orally inhaled ciclesonide (320 µg once daily) did not alter ciclesonide but resulted in a 3.5-fold increase in the AUC and a 2-fold increase in the Cmax of des-ciclesonide. Ciclesonide is mainly absorbed by the lungs, has a high protein binding and a high clearance resulting in a lower potential to cause systemic effects compared to some other inhaled corticosteroids. Hence, any interaction with lenacapavir would not require any dosage/therapy adjustments, particularly if ciclesonide is administered at lower or medium clinical doses, but close monitoring for Cushing’s syndrome signs is required when using a higher dose or with prolonged administration.

Coadministration has not been assessed in pharmacokinetic studies. Ciclosporin is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase ciclosporin concentrations which could increase or prolong its therapeutic and adverse effects. More frequent therapeutic concentration monitoring is recommended until plasma levels have been stabilised. A case report describes a kidney transplant patient whose ciclosporin blood concentration increased by ~60%, along with an increase in serum creatinine concentration, and the development of a fine tremor 2 weeks after starting fluvoxamine (another moderate CYP3A4 inhibitor) 100 mg daily; the ciclosporin dose was subsequently reduced by 33%. Ciclosporin concentrations could possibly change over lenacapavir dosing interval. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Ciclosporin is a sensitive CYP3A4 substrate and a narrow therapeutic index drug therefore ciclosporin TDM may still be needed in the initial weeks after stopping lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1, OAT3. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cimetidine is primarily eliminated by the kidneys (by MATE1). Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Cinacalcet does not inhibit or induce CYP3A4. However, concentrations of cinacalcet may increase due to inhibition of CYP3A4 by lenacapavir. A dose adjustment of cinacalcet may be required. Monitoring of iPTH serum phosphorus and serum calcium is recommended when starting or discontinuing lenacapavir. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Cinacalcet is not a sensitive CYP3A4 substrate and would not be expected to be significantly impacted by the residual concentrations of lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolized and partially cleared through the bile and intestine. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied and is not recommended. Cisapride is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase cisapride concentrations resulting in a higher risk for QT-prolongation/Torsade de Pointes. Cisapride has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website (known risk for cisapride). Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of cisapride even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

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.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE or OCTs in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), CYP2D6 (31%) and CYP3A4 (31%). Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C19 or CYP2D6 in the range of clinically significant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4, however, a clinically significant interaction is unlikely as citalopram is metabolized by multiple CYPs.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and P-gp. Clarithromycin is a strong inhibitor of CYP3A4 and P-gp. Coadministration of lenacapavir with darunavir/cobicistat (another strong CYP3A4 and P-gp inhibitor) increased lenacapavir exposure by 2.1-fold. This increase is deemed to be non-clinically relevant based on available safety data. Lenacapavir can be coadministered with clarithromycin without dose modification.

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

Coadministration has not been studied. Clindamycin is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% (after a loading dose of lenacapavir of 600 mg twice daily for 2 days) and has the potential to increase clindamycin concentrations, however, no a priori dose adjustment of clindamycin is needed.

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase chlordiazepoxide exposure. Monitor for side effects and decrease clobazam dose if necessary. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Clobazam is not a sensitive CYP3A4 substrate and would not be expected to be significantly impacted by the residual concentrations of lenacapavir.

Coadministration has not been studied. Clobetasol is a substrate of CYP3A4 and exposure may increase due to the moderate inhibition of CYP3A4 by lenacapavir. Topical clobetasol can be used with caution. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycaemia, and glycosuria in some patients. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid.

Coadministration has not been studied. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations. Clofazimine is a moderate inhibitor of CYP3A4 but this is unlikely to cause a clinically significant interaction as lenacapavir is a non-sensitive substrate of CYP3A4. Coadministration with voriconazole (a strong CYP3A4 inhibitor) increased lenacapavir exposure by 30%. This increase is not considered to be clinically relevant.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C19, CYP2D6 or CYP1A2 in the range of clinically significant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4, however, a clinically significant interaction is unlikely as clomipramine is metabolized by multiple CYPs.

Coadministration has not been studied. Clonazepam is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% (after a loading dose of lenacapavir of 600 mg twice daily for 2 days). Lenacapavir could increase clonazepam exposure, although to a lesser extent than midazolam, which could possibly prolong and/or increase pharmacologic effects of the benzodiazepine, including sedation and respiratory depression. Therapeutic concentration monitoring is recommended. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Clonazepam is not a sensitive CYP3A4 substrate and is not a narrow therapeutic index drug therefore residual concentrations of lenacapavir would not be expected to have a significant impact on clonazepam.

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). Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied but is not recommended. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP 3A4 and could reduce drug levels of the active metabolite of clopidogrel. Coadministration of clopidogrel with the strong CYP3A4 inhibitors ritonavir or cobicistat significantly decreased the concentrations of clopidogrel’s active metabolite. Importantly, the decrease in clopidogrel’s active metabolite led to insufficient inhibition of platelet aggregation in the patients treated with clopidogrel and ritonavir or cobicistat. This study suggests that lenacapavir could alter clopidogrel’s effect and therefore coadministration is not recommended. Of interest, a comparable decrease in prasugrel’s active metabolite was shown in presence of ritonavir or cobicistat, however, this decrease did not impair prasugrel’s antiplatelet effect. These data suggest that given the risk of diminished clopidogrel response, prasugrel should be preferred in presence of lenacapavir unless the patient has a clinical condition which contraindicates its use in which case an alternative antiplatelet agent should be considered.

Coadministration has not been studied. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase nordiazepam exposure. A low dose of clorazepate used cautiously is recommended with dose adjustment based on the clinical response. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of nordiazepam even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir is a moderate inhibitor of CYP3A4. Clotrimazole undergoes hepatic metabolism (likely via CYP3A4) and is also a moderate inhibitor of CYP3A4. A clinically significant increase in clotrimazole or lenacapavir is unlikely as both drugs already inhibit CYP3A4 to the same extent.

Coadministration has not been studied but a clinically significant interaction is unlikely with the topical use of clotrimazole as it is minimally absorbed.

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 renal elimination is approximately 35% of a dose. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP1A2, CYP2C19, CYP2C9 or CYP2D6 in the range of clinically relevant concentrations. Lenacapavir is a moderate CYP3A4 inhibitor and could increase clozapine exposure although to a limited extent. No a priori dosage adjustment is needed but monitoring of adverse effects is advised.

Coadministration has not been studied. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Lenacapavir is mainly cleared as unchanged drug but is a moderate inhibitor of CYP3A4 and may increase cobimetinib exposure. Coadministration should be avoided if possible. If coadministration is necessary, use with caution and close monitoring for safety. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Cobimetinib is a fairly sensitive CYP3A4 substrate, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Cocaine is metabolized by several pathways (CYP and non CYP mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase concentrations of the parent compound. The clinical relevance is unknown as cocaine is metabolized by other non-CYP mediated pathways. Ensure the patient is aware of signs/symptoms of cocaine toxicity.

Coadministration has not been studied. Codeine undergoes predominantly direct glucuronidation with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically relevant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4 but is not expected to cause a clinically significant increase in codeine exposure.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Coadministration has not been studied. Colchicine is metabolized by CYP3A4 and is a substrate of P-gp. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and a weak inhibitor of P-gp and may increase colchicine concentrations due to CYP3A4 inhibition. Colchicine’s label recommends a 2-fold reduction in colchicine dosage when co-administered with a moderate CYP3A4 inhibitor. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Colchicine is a sensitive CYP3A4 substrate and a narrow therapeutic index drug therefore caution is still needed in the initial months after stopping lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 but is unlikely to cause a significant interaction.

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. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 but is unlikely to cause a significant interaction with colecalciferol or the associated multivitamins.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Colesevelam can reduce the gastrointestinal absorption of some drugs. Colesevelam should be administered at least four hours before or after orally administered lenacapavir to minimize the risk of reduced absorption. No interaction is expected when lenacapavir is administered subcutaneously.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of oral lenacapavir should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for lenacapavir but for any medication taken with colestyramine.]

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Collagen hydrolysate is unlikely to affect CYP3A4 or UGT1A1.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase estrogens. The clinical significance of this increase in terms of overall risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women receiving substitution hormones in unknown. In addition, exposure of progestogens administered as part of HRT may also increase. The clinical relevance of this is unknown. The product label for lenacapavir mentions that no dose adjustment of estrogens and progestins is needed. The use of conjugated estrogens alone or in combination with a progestogen should be used at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for individual women. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Copanlisib is unlikely to affect lenacapavir elimination. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase copanlisib concentrations. Coadministration of copanlisib (60 mg i.v. infusion) and a strong CYP3A4 inhibitor (itraconazole, 200 mg once daily for 10 days) increased copanlisib AUC by 53% with no effect on Cmax (3% increase). A smaller increase may occur with lenacapavir. No a priori dose adjustment is needed but closely monitor patients for copanlisib toxicity. Note; if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Copanlisib is not a sensitive CYP3A4 substrate but is a narrow therapeutic index drug, therefore caution is still needed in the initial months after stopping lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Creatine is unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied. Crizotinib is mainly metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Both drugs can increase the exposure of each other although to a limited extent given that each inhibit CYP3A4. Simulations using physiologically based pharmacokinetic modelling showed that coadministration of crizotinib and diltiazem (another moderate CYP3A4 inhibitor) increased crizotinib exposure only by 1.1 fold. Lenacapavir could be impacted in a similar way. If coadministration is unavoidable, monitor closely for toxicity.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, however, this is unlikely to increase lenacapavir exposure to a clinically significant extent. Coadministration of the strong CYP3A4 inhibitor voriconazole (200 and 400 mg twice daily) with lenacapavir (300 mg oral dose) increased lenacapavir AUC and Cmax by 41% and 9%. These changes are not considered to be clinically relevant.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. No interaction is expected with cyanocobalamin.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. No interaction is expected with cyanocobalamin or the associated multivitamins.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

Coadministration has not been studied. Cyclophosphamide is metabolized by two pathways. Activation (major pathway) to 4-hydroxycyclophosphamide is catalyzed by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir could potentially reduce the risk of neurotoxicity and increase the amount of drug available for the activation pathway which may increase the efficacy and the toxicity of cyclophosphamide. Monitoring of cyclophosphamide related side effects is recommended. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of cyclophosphamide even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied. Cyproterone acetate is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase cyproterone exposure. A dose adjustment of cyproterone may be required. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods, however, cyproterone would not be expected to be significantly impacted by the residual concentrations of lenacapavir.

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

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

Coadministration has not been studied. Dabigatran is not metabolized by CYP450 enzymes and is mainly cleared by glomerular filtration. The prodrug of dabigatran is a substrate of P-gp. Lenacapavir is mainly cleared as unchanged drug and is a weak inhibitor of P-gp. Lenacapavir is not considered to be a meaningful inhibitor of P-gp therefore no a priori dose adjustment of dabigatran is needed. Furthermore, the product label for dabigatran indicates that no dose adjustment is required for dabigatran when coadministered with moderate inhibitors of P-gp. However, monitoring for increased dabigatran side effects is still recommended.

Coadministration has not been studied but is not recommended. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Dabrafenib is a strong inducer of CYP3A4 and may induce UGTs and therefore has the potential to decrease lenacapavir exposure which may result in loss of therapeutic effect and development of resistance and therefore coadministration is contraindicated. At least a 4-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a strong inducer.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. In vitro data indicate that dacarbazine is a substrate of the renal transporter OAT1. Lenacapavir is mainly cleared as unchanged drug and does not inhibit CYP1A1, CYP2E1 or the renal transporter OAT1 in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is partly metabolized by CYP3A4 and mainly eliminated unchanged in bile. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. However, based on drug interaction studies with strong CYP3A4 inhibitors, lenacapavir is unlikely to significantly alter daclatasvir exposure. No dose adjustment is needed.

Coadministration has not been studied. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Dacomitinib does not inhibit or induce CYP3A4 but inhibits UGT1A1 and may increase lenacapavir exposure, although to an extent that would not warrant a dose adjustment.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically significant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. 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.

Coadministration has not been studied. Dapoxetine is metabolized by CYP2D6, CYP3A4 and flavin monooxygenase 1. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase dapoxetine and desmethyldapoxetine exposures, especially in CYP2D6 poor metabolizers. The maximum dose of dapoxetine should be 30 mg if dapoxetine is combined with a moderate inhibitor such as lenacapavir. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of dapoxetine even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir is a moderate inhibitor of CYP3A4 but is unlikely to cause a clinically significant interaction as dapsone is eliminated via multiple CYP enzymes.

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

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. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied. Daridorexant is mainly metabolised by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Daridorexant is unlikely to have a significant effect on UGT1A1. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on lenacapavir. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase daridorexant concentrations. Coadministration of daridorexant (25 mg) with the moderate CYP3A4 inhibitor diltiazem (240 mg once daily) increased daridorexant AUC and Cmax by 2.4- and 1.4-fold, respectively. A similar effect is expected with lenacapavir and caution is advised. Product labels for daridorexant recommend a 25 mg dose of daridorexant when coadministered with moderate CYP3A4 inhibitors.

Coadministration has not been studied. Darifenacin is metabolized by CYP3A4 and CYP2D6. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase darifenacin concentrations. In presence of moderate CYP3A4 inhibitors, the recommended starting dose of darifenacin should be 7.5 mg daily. The dose may be titrated to 15 mg daily to obtain an improved clinical response provided the dose is well tolerated. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Darifenacin is a sensitive CYP3A4 substrate therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on lenacapavir. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase may increase darolutamide concentrations, but this is unlikely to be clinically significant. No a priori dose adjustment is required.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. This increase is not considered to be clinically relevant and does not warrant a dose adjustment. A similar increase is expected with darunavir/ritonavir.

Coadministration with Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of oral lenacapavir (300 mg single dose) with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. These increases are not considered to be clinically relevant and do not warrant a dose adjustment. No interaction is expected with emtricitabine.

Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of oral lenacapavir (300 mg single dose) with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. This increase is not considered to be clinically relevant and does not warrant a dose adjustment.

Coadministration has not been studied. Dasatinib is metabolized by CYP3A4 and is a weak inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase dasatinib exposure. Concurrent use of CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, monitor closely for dasatinib side effects and dose reduction should be considered. Consider monitoring of dasatinib plasma concentrations, if available. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Dasatinib is a sensitive CYP3A4 substrate and therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An in vitro study has shown that daunorubicin was able to inhibit metabolism mediated by CYP3A4, but was unlikely to cause clinically significant drug interactions via this mechanism. Lenacapavir is a moderate inhibitor of CYP3A4 but a clinical study showed that the CYP3A4 inhibitors indinavir, saquinavir or ritonavir did not significantly affect liposomal daunorubicin pharmacokinetics.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Decitabine does not inhibit or induce CYP enzymes.

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%). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease lenacapavir concentrations. Deferasirox and lenacapavir are unlikely to affect UGTs.

Coadministration has not been studied. 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%). Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Deflazacort and 21-desdeflazacort do not inhibit or induce CYP3A4 or UGT1A1. However, lenacapavir is a moderate inhibitor of CYP3A4 and may increase exposure of 21-desdeflazacort. Coadministration of deflazacort and clarithromycin (a strong CYP3A4 inhibitor), increased total exposure of 21-desdeflazacort by about 3-fold. The European product label for deflazacort recommends coadministration with CYP3A inhibitors should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects. The US product label suggests a dose reduction to one third of the normal recommended deflazacort dosage with moderate/strong CYP3A4 inhibitors.

Coadministration has not been studied. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase delamanid and DM-6705 concentrations, although to a limited extent that is not expected to increase the risk of QT prolongation.

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.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically significant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolized by CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase etonogestrel and ethinylestradiol exposures, although to an extent that does not require dose adjustment.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase etonogestrel exposure, although to an extent that does not require dose adjustment.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs, CYP2C19 in the range of clinically significant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4, however, a clinically significant interaction is unlikely given the multiple elimination pathways.

Coadministration has not been studied and is not recommended. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Dexamethasone is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and has the potential to increase exposure of dexamethasone and the related risk of Cushing’s syndrome and adrenal suppression. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg and could potentially decrease lenacapavir concentrations. A reduction in lenacapavir concentrations may result in loss of therapeutic effect and development of resistance and therefore coadministration is not recommended. At least a 2-week cessation period is recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a moderate inducer.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Dexamethasone is metabolized by CYP3A4. Dexamethasone is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and has the potential to increase exposure of dexamethasone and the related risk of Cushing’s syndrome and adrenal suppression. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on lenacapavir.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not inhibit or induce UGTs or CYP2C8/9. Dexketoprofen is unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Absorption of lenacapavir is unlikely to be influenced by changes in gastric pH.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGT1A4 and UGT2B10) and cytochrome P450 (mainly CYP2A6). Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir is unlikely to affect CYP2D6. Dextromethorphan is unlikely to affect lenacapavir elimination.

Coadministration has not been studied and is not recommended. Dextropropoxyphene has been withdrawn from most European and North American countries due to the risk of arrhythmias and fatalities. Dextropropoxyphene is mainly metabolized by CYP3A4 and concentrations may increase as lenacapavir is a moderate inhibitor of CYP3A4. Lenacapavir increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308%. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Therefore, caution is recommended as residual concentrations of lenacapavir could potentially affect dextropropoxyphene.

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). Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically relevant concentrations.

Coadministration has not been studied. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Coadministration of diltiazem (another moderate CYP3A4 inhibitor) increased diazepam AUC by 24%. A similar effect is expected with lenacapavir but no a priori dose adjustment is needed.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs or CYP2C9 in the range of clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diethylcarbamazine is mainly excreted unchanged in the urine. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a weak inhibitor of P-gp. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-gp. Lenacapavir is not considered to be a meaningful inhibitor of P-gp therefore no a priori dose adjustment of digoxin is needed. However, the product label for lenacapavir recommends therapeutic drug monitoring of digoxin.

Coadministration has not been studied. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. Lenacapavir is mainly cleared as unchanged drug. Lenacapavir does not inhibit or induce CYP2D6 or UGTs in the range of clinically significant concentrations. Lenacapavir is a moderate inhibitor of CYP3A4 but is not expected to cause a significant increase in dihydrocodeine concentrations due to the multiple metabolic pathways of dihydrocodeine. No a priori dose adjustment is required, but monitoring for opiate toxicity is recommended as clinically indicated.

Coadministration has not been studied and is not recommended. If coadministration is necessary the combination should be used with extreme caution. Dihydroergotamine is metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and increased exposure of midazolam (a sensitive CYP3A4 substrate) by 259-308% (after a loading dose of lenacapavir of 600 mg twice daily for 2 days). Thus, lenacapavir has the potential to increase dihydroergotamine exposure. Use with extreme caution due to the potential increased risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These concentrations may affect the exposure of dihydroergotamine even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

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 subsequently glucuronidated. No clinically significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and CYP2D6, and is a moderate inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir may increase diltiazem concentrations, although to a limited extent given that diltiazem also inhibits CYP3A4. No a priori dose adjustment is needed

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce UGTs in the range of clinically relevant concentrations.

Coadministration has not been studied but is not recommended. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine possibly via OCT2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations. However, lenacapavir is a moderate inhibitor of CYP3A4 and could increase disopyramide concentrations and the potential related risk of cardiotoxicity. The product label for disopyramide recommends to avoid coadministration with CYP3A4 inhibitors. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of the narrow therapeutic index drug disopyramide even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

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. Significant interactions are not expected with lenacapavir.

Coadministration has not been studied. Docetaxel is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase docetaxel concentrations and the related risk of toxicities. No a priori dose adjustment is needed, however, monitor for docetaxel side effects. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Docetaxel is not a sensitive CYP3A4 substrate but is a narrow therapeutic index drug therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied and is contraindicated. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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%). Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinical concentrations. Lenacapavir is a moderate inhibitor of CYP3A4 but this is unlikely to cause a clinically significant interaction as multiple pathways are involved in dolasetron metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. This increase is not considered to be clinically relevant. A similar effect is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine and abacavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine.

Coadministration has not been studied. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Rilpivirine is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4 and could potentially increase rilpivirine, although to an extent that is not considered to be clinically relevant. No dose adjustment is a priori needed.

Coadministration of domperidone with moderate CYP3A4 inhibitors such as lenacapavir has not been studied and is not recommended. Domperidone is mainly metabolized by CYP3A4. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase domperidone concentrations and increase the risk of cardiac adverse effects. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. These residual concentrations may affect the exposure of sensitive CYP3A4 substrates that are initiated within 9 months after the last dose subcutaneous dose of lenacapavir. Domperidone is a fairly sensitive CYP3A4 substrate, therefore caution is still needed in the initial months after stopping lenacapavir.

Coadministration has not been studied. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase donepezil concentrations, although to a limited extent. No a priori dose adjustment is required. However, caution should be exercised as donepezil has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Donepezil is not a sensitive CYP3A4 substrate and is not a narrow therapeutic index drug and would not be expected to be significantly impacted by the residual concentrations of lenacapavir.

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. Lenacapavir does not interact with this metabolic pathway.

Coadministration has not been studied. Doravirine is mainly metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could increase doravirine exposure, although to an extent that is unlikely to be clinically significant. Phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Doravirine is mainly metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and therefore could increase doravirine exposure although to an extent that is unlikely to be clinically significant. Phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. Furthermore, no clinically significant interactions are expected with lamivudine or tenofovir-DF. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. This increase is not considered to be clinically relevant. A similar effect is expected with tenofovir-DF.

Coadministration has not been studied. Doxazosin is metabolized mainly by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase doxazosin concentrations. No a priori dose adjustment is recommended, however, monitoring of blood pressure could be considered. Note, if lenacapavir is discontinued, residual concentrations of lenacapavir may remain in the circulation for prolonged periods. Thus, these concentrations may affect the exposure of doxazosin even if it is initiated within 9 months after the last dose subcutaneous dose of lenacapavir.

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. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 or CYP2C19 in the range of clinically significant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and a weak inhibitor of P-gp. Doxorubicin is mainly eliminated in the bile 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.) Doxorubicin is a substrate of P-glycoprotein, however, coadministration with protease inhibitors did not modify significantly doxorubicin exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Lenacapavir is mainly cleared as unchanged drug and does not inhibit the renal transporters MATE, OCTs, OATs, BCRP in the range of clinically relevant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Lenacapavir does not inhibit or induce CYP2D6, CYP1A2 or CYP2C9 in the range of clinically relevant concentrations. Doxylamine is unlikely to have a clinically significant effect on lenacapavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on UGTs in the range of clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2C9 in the range of clinical concentrations. Lenacapavir is a moderate inhibitor of CYP3A4 and may increase dronabinol exposure, although to an extent that is unlikely to be clinically relevant.

Coadministration has not been studied. Dronedarone is metabolised and is a moderate inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4. Lenacapavir may increase dronedarone concentrations, although to a limited extent given that dronedarone also inhibits CYP3A4. Coadministration with the moderate CYP3A4 inhibitors diltiazem (240 mg twice daily), verapamil (240 mg once daily) and nifedipine (20 mg twice daily) increased dronedarone exposure by 1.7-, 1.4- and 1.2-fold, respectively. A similar effect may occur with lenacapavir. Use with caution.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase drospirenone as well as the ethinylestradiol component, although to an extent that does not require dose adjustment.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase drospirenone as well as the estradiol or estrogens component administered as part of HRT, although to an extent that does not require dose adjustment.

Coadministration with a drospirenone progestogen-only pill (POP) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase drospirenone exposure, although to an extent that does not require dose adjustment.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 or CYP1A2 in the range of clinically significant concentrations.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. No metabolic drug interactions are expected with dupilumab.

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. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied. Dutasteride is mainly metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and may increase dutasteride concentrations. Dutasteride has a large therapeutic index, therefore no a priori dose adjustment is needed.

Coadministration has not been studied. Duvelisib is primarily metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of lenacapavir with darunavir/cobicistat (another strong CYP3A4 inhibitor) increased lenacapavir exposure by 2.1 fold. A similar increase may occur with duvelisib. This increase is deemed to be non-clinically relevant based on available safety data therefore no dose adjustment is needed for lenacapavir.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase dydrogesterone or the estradiol/estrogens component, although to an extent that does not require dose adjustment.

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. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Ecdysterone is unlikely to affect CYP3A4 or UGT1A1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Studies using a cocktail of probe drugs showed Echinacea inhibited CYP1A2 and intestinal CYP3A activity, and induced hepatic CYP3A activity. However, coadministration of Echinacea and the strong CYP3A4 inhibitor lopinavir/ritonavir showed no clinically significant effect of Echinacea on lopinavir or ritonavir concentrations (most likely due to the potent CYP3A inhibition by ritonavir). Based on these data, Echinacea is unlikely to alter lenacapavir exposure as it is a moderate inhibitor of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and does not inhibit or induce CYP2D6 in the range of clinically relevant concentrations.

Coadministration has not been studied. Edoxaban is eliminated primarily as unchanged drug in urine and is minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%). Edoxaban is a substrate of P-gp. Lenacapavir is mainly cleared as unchanged drug and is a weak inhibitor of P-gp. Lenacapavir is not considered to be a meaningful inhibitor of P-gp therefore no a priori dose adjustment of dabigatran is needed. However, monitoring for increased edoxaban side effects is still recommended.

Coadministration is not recommended as it may impair lenacapavir efficacy. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Coadministration with efavirenz (a moderate CYP3A4 and UGT inducer) decreased lenacapavir AUC and Cmax by 56% and 36%. Although at least a 2-week cessation period is usually recommended prior to initiation of lenacapavir due to the persisting inducing effect after discontinuation of a moderate inducer, at least a 4-week cessation period is recommended prior to initiation of lenacapavir following discontinuation of efavirenz due to the long half life of efavirenz.