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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Abemaciclib has no inhibitory or inducing effects on CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Fostemsavir does not interact with these metabolic pathways.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Abrocitinib is not expected to have a clinically relevant effect on CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Acalabrutinib has no inhibitory or inducing effects on CYPs at clinically relevant concentrations.

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 fostemsavir should be separated by 4 hours. [Note: this interaction is not specific for fostemsavir, but for any oral medication taken with activated charcoal.]

Coadministration has not been studied. Afatinib is mainly eliminated unchanged in the faeces and is a substrate of P-gp and BCRP. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir inhibits BCRP and has the potential to increase afatinib exposure. Use with caution.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP3A4 enzyme. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Alfuzosin has a possible risk of QTc prolongation on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with alfuzosin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Alprostadil is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied. Amiodarone is metabolized by CYPs 3A4 and 2C8, but temsavir (the active metabolite of fostemsavir) does not inhibit or induce CYP enzymes. Amiodarone is a P-gp inhibitor and coadministration is expected to increase temsavir concentrations but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 and P-gp inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with amiodarone. However, given the known QT prolongation risk associated with amiodarone, ECG monitoring is recommended when coadministering both drugs.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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 temsavir is expected and no a priori dose adjustment is required.

Coadministration has not been studied but coadministration with strong CYP3A inducers is contraindicated in the product labels for fostemsavir. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Coadministration with apalutamide may substantially reduce temsavir exposure which may result in a potential loss of therapeutic effect. 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 fostemsavir due to the persisting inducing effect upon discontinuation of a strong inducer. Furthermore, fostemsavir has been associated with prolongation of the QT interval at supra-therapeutic doses and androgen deprivation therapy may prolong the QT interval.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce drug metabolizing enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Apomorphine has a possible risk of QTc prolongation on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with apomorphine.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4, however, 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 orally administered antiretroviral drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect from day 8 which is clinically insignificant by two weeks. Any transient change in temsavir exposure is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Aripiprazole has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with aripiprazole.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect arsenic trioxide metabolism. Arsenic trioxide is unlikely to affect fostemsavir or temsavir metabolism. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses although these are unlikely to occur during coadministration with arsenic trioxide. However, given arsenic trioxide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. QT prolongation has been reported in patients receiving asciminib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, CYP2D6 (minor)). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Asenapine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with asenapine.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Ashwagandha extracts had no effect on CYP enzymes in vitro.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with astemizole. However, given the known QT prolongation risk associated with astemizole, ECG monitoring is recommended when coadministering both drugs.

Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir (600 mg twice daily) and atazanavir/ritonavir (300/100 mg once daily) increased temsavir Cmax, AUC and Cmin by 68%, 54% and 57%, but did not alter significantly atazanavir (Cmax, AUC and Cmin increased by 3%, 9% and 19%) and ritonavir (Cmax, AUC and Cmin increased by 2%, 7% and 22%). Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with atazanavir/ritonavir. Thus, the increase in fostemsavir exposure is not considered to be clinically significant and does not warrant a dose adjustment of fostemsavir.

Coadministration of fostemsavir and atazanavir alone has not been studied. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir (600 mg twice daily) and atazanavir/ritonavir (300/100 mg once daily) increased temsavir Cmax, AUC and Cmin by 68%, 54% and 57%, but did not alter significantly atazanavir (Cmax, AUC and Cmin increased by 3%, 9% and 19%) and ritonavir (Cmax, AUC and Cmin increased by 2%, 7% and 22%). Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with atazanavir. Thus, the increase in fostemsavir exposure is not considered to be clinically significant and does not warrant a dose adjustment of fostemsavir.

Coadministration of fostemsavir and atazanavir/cobicistat has not been studied. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir and atazanavir/ritonavir increased temsavir Cmax, AUC and Cmin by 68%, 54% and 57%, but did not alter significantly atazanavir (Cmax, AUC and Cmin increased by 3%, 9% and 19%) and ritonavir (Cmax, AUC and Cmin increased by 2%, 7% and 22%). A similar effect is expected with atazanavir/cobicistat. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with atazanavir/cobicistat. Thus, the increase in fostemsavir exposure is not considered to be clinically significant and does not warrant a dose adjustment of fostemsavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir and neratinib do not inhibit or induce CYP enzymes. Atogepant is not expected to have a clinically relevant effect on drugs metabolized by CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Atomoxetine is metabolized by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Atomoxetine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with fostemsavir.

Coadministration has not been studied. Atorvastatin is metabolized by CYP3A4 and is a substrate of OATPs. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4 enzymes. Temsavir does not inhibit or induce CYP enzymes but does inhibit OATPs and BCRP and has the potential to increase atorvastatin exposure. Use the lowest possible starting dose and monitor for statin associated adverse events.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Avatrombopag does not inhibit or induce CYP3A.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir has no inhibitory or inducing effects on drug metabolizing enzymes. Axitinib does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. In vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4 and could potentially increase the exposure of temsavir, but this is unlikely to be clinically significant.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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. Azilsartan is metabolized mainly by CYP2C9. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-gp and MRP2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit MRP2 and P-gp. Azithromycin is not a significant inhibitor of CYP3A4 or P-gp and is not expected to impact temsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with azithromycin. However, given the known QT prolongation risk associated with azithromycin, ECG monitoring is recommended when coadministering both drugs.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes.

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on norethindrone (1.5 mg once daily) exposure, but increased ethinylestradiol (0.030 mg once daily) Cmax and AUC by 39% and 40% (possibly due to BCRP inhibition). Similarly, an increase in exposure of bazedoxifene or conjugated estrogens cannot be excluded. Bazedoxifene alone or with conjugated estrogens 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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bedaquiline has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with bedaquiline.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Patients requiring treatment with belimumab may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Belimumab was shown to lower IFN and IL-6/10 and is expected to normalize metabolism but no significant effect on temsavir is expected and no a priori dose adjustment is required when initiating or discontinuing belimumab.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Bempedoic acid does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir and bendamustine do not inhibit or induce CYP enzymes. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bendamustine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benzonatate is metabolized by plasma butyrylcholinesterase. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect benzonatate metabolism. Benzonatate is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bepridil is metabolized by CYPs 2D6 (major) and 3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with bepridil. However, given the known QT prolongation risk associated with bepridil, ECG monitoring is recommended when coadministering both drugs.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Beta-alanine is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. However, betamethasone is a moderate inducer of CYP3A4 but is unlikely to alter temsavir exposure significantly. Coadministration of fostemsavir with rifabutin (a moderate inducer) was shown to reduce the exposure of the active metabolite temsavir by 30%. This decrease was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. This recommendation also applies when fostemsavir is coadministered with betamethasone. 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 fostemsavir.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit P-gp. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Betrixaban has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with betrixaban.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Bicalutamide is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on temsavir. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as fostemsavir (although at supra-therapeutic concentrations).

Bictarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Bictegravir is metabolized by CYP3A4 and UGT1A1 whereas emtricitabine and tenofovir alafenamide are eliminated renally. Bictegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Fostemsavir may increase tenofovir alafenamide exposure (due to intestinal inhibition of BCRP by temsavir) but to a modest extent with no clinically relevant impact. No interaction is expected with emtricitabine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Bilastine is unlikely to affect fostemsavir or temsavir metabolism. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bilastine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with bilastine.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce UGT or CYP enzymes. 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 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Bismuth subsalicylate is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. No effect on temsavir is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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 but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYPs 3A4 and 2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bortezomib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with bortezomib.

Coadministration has not been studied. Bosentan is a substrate CYP3A4 and OATP1B1. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes but does inhibit OATP1B1 and has the potential to increase bosentan exposure. When coadministered patients should be closely monitored for bosentan toxicity, especially during the first week of co-administration. Bosentan is a moderate inducer of CYP3A4 but is unlikely to alter temsavir exposure significantly. Coadministration of fostemsavir with rifabutin (a moderate inducer) was shown to reduce the exposure of the active metabolite temsavir by 30%. This decrease was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. This recommendation does also apply when fostemsavir is coadministered with bosentan.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bosutinib is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Bosutinib has no inhibitory or inducing effects on CYPs. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bosutinib has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with bosutinib.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. BCAAs are unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with fostemsavir. MMAE is a substrate of CYP3A4 and P-gp, but no interaction is expected as temsavir, the active metabolite of fostemsavir, has no inhibitory or inducing effects on CYP3A4. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Brexpiprazole is unlikely to have a clinically relevant effect on drugs metabolised by CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brigatinib is metabolised by CYP2C8 and CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Brigatinib is a weak inhibitor of CYP3A4 but is unlikely to cause a clinically significant increase in temsavir exposure.

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. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Fostemsavir does not affect this pathway. However, brincidofovir is a substrate of OATP1B1 and concentrations may increase due to inhibition of OATP1B1 by fostemsavir. If concomitant use with brincidofovir is necessary, increase the monitoring for adverse reactions associated with brincidofovir (i.e. elevations in transaminases and bilirubin, diarrhoea, or other gastro-intestinal adverse events) and postpone the dosing of fostemsavir for at least 3 hours after brincidofovir

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect CYPs. Brinzolamide is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Bromocriptine is unlikely to affect fostemsavir or temsavir metabolism. Fostemsavir and temsavir do not inhibit or induce CYP3A4.

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%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration of fostemsavir (600 mg twice daily) in 16 individuals on stable buprenorphine/naloxone treatment (doses between 8/2 and 24/6 mg once daily) increased Cmax, AUC and C24 of buprenorphine by 24%, 30% and 39% and those of norbuprenorphine by 24%, 39% and 36%. These changes are not considered to be clinically relevant and were not associated with opioid withdrawal effects or with toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect busulfan metabolism. Busulfan is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Cabazitaxel has no inhibitory or inducing effects on CYPs at clinically relevant concentrations.

Coadministration has not been studied. Cabergoline is extensively metabolized by the liver, predominantly via hydrolysis (non-CYP mediated metabolism), and is a substrate of P-gp. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes or P-gp. No effect on fostemsavir is expected as cabergoline 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 by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine is metabolized by CYP3A4 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir and rilpivirine have been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration. However, the product labels indicate that these antiretroviral drugs should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cabozantinib is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Cabozantinib has no inhibitory or inducing effects on CYPs. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Cabozantinib has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with cabozantinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir do not affect CYP1A2. Caffeine is unlikely to affect fostemsavir or temsavir metabolism.

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. Fostemsavir does not interfere with this pathway.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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 temsavir 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. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Capecitabine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with capecitabine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capmatinib is primarily metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Capmatinib is unlikely to have a clinically relevant effect on CYP3A4.

Coadministration has not been studied but is contraindicated. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir with rifampicin (another strong inducer) substantially decreased temsavir Cmax and AUC by 76% and 88%. A similar effect is expected with the strong inducer carbamazepine, therefore, coadministration is contraindicated as it may result in a potential loss of therapeutic effect.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Cariprazine is unlikely to affect fostemsavir or temsavir metabolism. Fostemsavir and temsavir do not inhibit or induce CYP3A4 or CYP2D6.

Coadministration has not been studied. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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. However, cat’s claw is unlikely to significantly increase temsavir. Coadministration of fostemsavir with ritonavir (a strong CYP3A4 inhibitor) was shown to increase temsavir Cmax, AUC and Cmin by 53%, 45% and 44%. These changes were not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir.

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). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. Cedazuridine does not inhibit or induce CYP enzymes.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater may substantially reduce temsavir exposure which may result in a potential loss of therapeutic effect.

Coadministration has not been studied. Ceritinib is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Ceritinib could increase temsavir but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Ceritinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Patients requiring treatment with certolizumab pegol may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Certolizumab pegol will normalize cytochrome activity (via reduction of cytokines) but no significant effect on temsavir is expected and no a priori dose adjustment is required when initiating or discontinuing certolizumab pegol.

Coadministration with a chlormadinone -containing combined oral contraceptive (COC) has not been studied. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on norethindrone (1.5 mg once daily) exposure, but increased ethinylestradiol (0.030 mg once daily) Cmax and AUC by 39% and 40% (possibly due to BCRP inhibition). The ethinylestradiol daily dose should not exceed 30 µg. Caution is advised particularly in patients with additional risk factors for thromboembolic events.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with chloroquine. However, given the known QT prolongation risk associated with chloroquine, ECG monitoring is recommended when coadministering both drugs. Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with chlorpromazine. However, given the known QT prolongation risk associated with chlorpromazine, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Cinacalcet does not inhibit or induce CYP3A4. Note, decreases in serum calcium may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as fostemsavir (although at supra-therapeutic concentrations).

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys by glomerular filtration and tubular secretion via OAT3. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit OAT3. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with ciprofloxacin. However, given the known QT prolongation risk associated with ciprofloxacin, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cisapride is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cisapride. However, given the known QT prolongation risk associated with cisapride, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with citalopram. However, given the known QT prolongation risk associated with citalopram, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied. Clarithromycin is a strong inhibitor of CYP3A4 and P-gp and coadministration is predicted to increase temsavir (the active metabolite of fostemsavir) but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 and P-gp inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with clarithromycin. However, given the known QT prolongation risk associated with clarithromycin, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Clofazimine is a moderate inhibitor of CYP3A4 and may increase temsavir but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 and P-gp inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clofazimine has a conditional risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with clofazimine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clozapine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with clozapine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. Cobimetinib is unlikely to have a clinically relevant effect on CYP3A4. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Cobimetinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cocaine. However, given the known QT prolongation risk associated with cocaine, ECG monitoring is recommended when coadministering both drugs.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after fostemsavir to minimize the risk of reduced absorption.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for fostemsavir, 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Collagen hydrolysate is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on norethindrone (1.5 mg once daily) exposure, but increased ethinylestradiol (0.030 mg once daily) Cmax and AUC by 39% and 40% (possibly due to BCRP inhibition). Similarly, no effect on progestogens is expected but an increase in exposure of conjugated estrogens cannot be excluded. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect CYPs. Copanlisib is unlikely to affect fostemsavir or temsavir metabolism.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Creatine is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied. Crizotinib is mainly metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Crizotinib could increase temsavir but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Crizotinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclobenzaprine is primarily metabolized by CYP3A4 and CYP1A2 and to a lesser extent by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir do not inhibit or induce CYP enzymes. Cyclobenzaprine is unlikely to affect fostemsavir or temsavir metabolism.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied but is not recommended. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Dabrafenib is a strong inducer of CYP3A4 and therefore has the potential to decrease temsavir exposure which can result in a potential loss of therapeutic effect. Furthermore, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dabrafenib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is partly metabolized by CYP3A4 and mainly eliminated unchanged in bile. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.Temsavir does not inhibit or induce CYP enzymes. Dacomitinib does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daridorexant is mainly metabolised by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on temsavir. Fostemsavir and temsavir do not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on temsavir. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as fostemsavir (although at supra-therapeutic concentrations).

Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir with darunavir/ritonavir (600/100 mg twice daily) increased temsavir Cmax, AUC and Cmin by 52%, 63% and 88%. These changes are not considered to be clinically significant and warrant a dose adjustment of fostemsavir. Fostemsavir did not significantly alter the pharmacokinetics of darunavir (Cmax, AUC and Cmin decreased by 2%, 6% and 5%) or ritonavir (AUC and Cmin increased by 15%, 19% whereas Cmax was unchanged). Of interest, coadministration of fostemsavir with darunavir/ritonavir (600/100 mg twice daily) plus etravirine (200 mg twice daily) increased temsavir Cmax, AUC and Cmin by 53%, 34% and 33%. These changes were also not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir had no significant effect on the pharmacokinetics of darunavir (Cmax, AUC and Cmin decreased by 5%, 6% and 12%), ritonavir (Cmax, AUC and Cmin increased by 14%, 9% and 7%) or etravirine (Cmax, AUC and Cmin increased by 18%, 28% and 28%).

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir with darunavir/cobicistat increased temsavir Cmax, AUC and Cmin by 79%, 97% and 124%. These changes were not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir may increase tenofovir alafenamide exposure (due to intestinal inhibition of BCRP by temsavir), but to a modest extent with no clinically relevant impact. No interaction is expected with emtricitabine.

Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir (600 mg twice daily) with darunavir/cobicistat (800/150 mg once daily) increased temsavir Cmax, AUC and Cmin by 79%, 97% and 124% (n=15). These changes are not considered to be clinically significant and do not warrant a dose adjustment of fostemsavir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dasatinib is metabolized by CYP3A4 and is a weak inhibitor of CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with dasatinib.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect UGTs. Deferasirox is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Deflazacort and 21-desdeflazacort-are unlikely to affect fostemsavir or temsavir metabolism. Fostemsavir and temsavir are unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Delamanid has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with delamanid.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desipramine is metabolized by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with desipramine.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Desloratadine does not inhibit CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg, but is unlikely to alter temsavir exposure significantly. Coadministration of fostemsavir with rifabutin (a moderate inducer) was shown to reduce the exposure of the active metabolite temsavir by 30%. This decrease was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. This recommendation also applies when fostemsavir is coadministered with dexamethasone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on fostemsavir.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir do not inhibit or induce UGTs or CYP2C8/9. Dexketoprofen is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Dexlansoprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor) and is unlikely to alter absorption of fostemsavir. Coadministration of fostemsavir 2 hours after famotidine (40 mg single dose) under fasted conditions did not significantly alter temsavir pharmacokinetics (Cmax increased by 1%, AUC increased by 4%, Cmin decreased by 10%). Thus, temsavir solubility is not impacted by changes in pH and can be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Fostemsavir and temsavir are unlikely to affect CYP2D6. Dextromethorphan is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Diltiazem is a strong inhibitor of CYP3A4 but is not expected to cause a clinically significant increase in temsavir. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Diltiazem has a conditional risk of QTc prolongation on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with diltiazem.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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 pharmacokinetic interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine possibly via OCT2. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes and does not inhibit OCT2. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with disopyramide. However, given the known QT prolongation risk associated with disopyramide, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Docusate has been reported to undergo extensive first-pass metabolism and metabolism in the liver, but the metabolic pathway remains unclear. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Docusate is unlikely to affect fostemsavir or temsavir metabolism.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit the organic cation transporters. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with dofetilide. However, given the known QT prolongation risk associated with dofetilide, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses and the product label for fostemsavir indicates that fostemsavir should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. An interaction to increase QTc prolongation is unlikely to occur with dolasetron.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. Coadministration of fostemsavir with tenofovir disoproxil fumarate was shown to have no significant effect on temsavir pharmacokinetics. In contrast, fostemsavir increased tenofovir disoproxil fumarate Cmax, AUC and Cmin by 18%, 19% and 28% respectively but these changes are not considered to be clinically relevant. No interaction is expected with lamivudine.

Triumeq (dolutegravir/abacavir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. No interaction is expected with lamivudine or abacavir.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. No interaction is expected with lamivudine.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. Fostemsavir and rilpivirine have been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration. However, the product labels indicate that these antiretroviral drugs should be used with caution in combination with drugs with a known risk of Torsade de Pointes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with domperidone. However, given the known QT prolongation risk associated with domperidone, ECG monitoring is recommended when coadministering both drugs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. However, fostemsavir has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with donepezil. Given the known QT prolongation risk associated with donepezil, ECG monitoring is recommended when coadministering both drugs.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with fostemsavir would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected. Doravirine is metabolized by CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP or UGT enzymes. Coadministration of fostemsavir with tenofovir disoproxil fumarate was shown to have no significant effect on temsavir pharmacokinetics. In contrast, fostemsavir increased tenofovir disoproxil fumarate Cmax, AUC and Cmin by 18%, 19% and 28% but these changes are not considered to be clinically relevant. No interaction is expected with lamivudine.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Doxylamine is unlikely to have a clinically significant effect on fostemsavir or temsavir.

Coadministration has not been studied. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Dronedarone is a moderate inhibitor of CYP3A4 and P-gp but is not expected to cause a clinically significant increase in temsavir. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on norethindrone (1.5 mg once daily) exposure, but increased ethinylestradiol (0.030 mg once daily) Cmax and AUC by 39% and 40% (possibly due to BCRP inhibition). Similarly, no effect on drospirenone is expected but an increase in exposure of estradiol/estrogen (given with drospirenone as HRT) cannot be excluded. The use of estradiol/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.

Coadministration with a drospirenone progestogen-only pill (POP) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on exposure of norethindrone (1.5 mg once daily).

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolised by esterase-mediated hydrolysis with a small contribution of CYP3A4.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. 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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4.

Coadministration has not been studied. Duvelisib is primarily metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Duvelisib could increase temsavir but to a modest extent. Coadministration of fostemsavir with cobicistat (a strong CYP3A4 inhibitor) increased temsavir exposure by 93%. This increase was not considered to be clinically significant and did not warrant a dose adjustment of fostemsavir.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir had no significant effect on norethindrone (1.5 mg once daily) exposure, but increased ethinylestradiol (0.030 mg once daily) Cmax and AUC by 39% and 40% (possibly due to BCRP inhibition). Similarly, no effect on dydrogesterone is expected but an increase in exposure of estradiol/estrogen (given with dydrogesterone as HRT) cannot be excluded. The use of estradiol/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.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Ecdysterone is unlikely to affect fostemsavir or temsavir metabolism.