Coadministration has not been studied but based on metabolism and clearance a clinically relevant interaction is unlikely. Abacavir is metabolized by alcohol dehydrogenase and UGT. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP or other hepatic metabolism described. A high rate of virological failure and emergence of resistance have been reported when lamivudine was combined with tenofovir-DF and abacavir as a once-daily regimen. However, this is not relevant when tenofovir alafenamide is prescribed for HBV.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone has multiple metabolic pathways and is an inhibitor of CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. Tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1 such as abiraterone may affect the distribution of tenofovir alafenamide in the body. The clinical relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aceclofenac is metabolised by CYP2C9. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this route are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. LSD (lysergic acid diethylamide) is metabolised to O-H-LSD and N-desmethyl-LSD partly by CYP (unknown isoenzyme). Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

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

Coadministration has not been studied and is contraindicated. Tenofovir alafenamide should not be used concomitantly with adefovir dipivoxil.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, agomelatine is contraindicated in hepatic impairment as increases in exposure of up to 140-times have been seen in cirrhotic patients.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albiglutide is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by ubiquitous proteolytic enzymes. Albiglutide slows gastric emptying, but this is unlikely to have a clinically relevant effect on tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. Acute alcohol use inhibits CYP2E1. Chronic use may induce CYP2E1 and to a lesser extent CYP3A4 but this is unlikely to be clinically relevant. Tenofovir alafenamide does not interact with these pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no other hepatic metabolism described. [Note, the European SmPC and US Prescribing Information for allopurinol recommend a reduced dose in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated renally by glomerular filtration. Coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A. Anakinra does not interact with these pathways. Anakinra is an IL-1 receptor antagonist and is eliminated by glomerular filtration and subsequent tubular metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phencyclidine is extensively metabolised to inactive metabolites by a variety of metabolic routes (mainly CYP3A4). Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apalutamide is metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP or other hepatic metabolism described. Apalutamide is a weak P-gp/BCRP inducer which may decrease tenofovir alafenamide plasma concentrations, although to a moderate extent. No a priori dose adjustment of tenofovir alafenamide is needed as coadministration with rifampicin (a stronger inducer) led to lower intracellular tenofovir diphosphate concentrations but which were still higher than those achieved with tenofovir disoproxil fumarate. [Note, use of apalutamide in severe hepatic impairment is not recommended in the European SmPC.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydroartemisinin (the active metabolite of artesunate) is further metabolised via UGT1A9 and 2B7 and has been shown to induce CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP or other hepatic metabolism described. Tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1 such as artesunate may affect the distribution of tenofovir alafenamide in the body, but this is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration is not recommended. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and tenofovir alafenamide (10 mg) increased tenofovir AUC and Cmax by 91% and 77%. No significant effects were observed on atazanavir pharmacokinetics. The European SmPC states that coadministration is not recommended but atazanavir/ritonavir is not mentioned in the US PI. This checker reflects the more cautious option.

Coadministration has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and tenofovir alafenamide alone (10 mg) increased tenofovir AUC and Cmax by 91% and 77%. Coadministration of atazanavir/cobicistat (300/150 mg once daily) and tenofovir alafenamide increased tenofovir alafenamide AUC and Cmax by 75% and 80%. No significant effects were observed on atazanavir pharmacokinetics.

Coadministration is not recommended. Coadministration of atazanavir/cobicistat (300/150 mg once daily) and tenofovir alafenamide increased tenofovir alafenamide AUC and Cmax by 75% and 80%. No significant effects were observed on atazanavir pharmacokinetics. The European SmPC states that coadministration is not recommended but atazanavir/cobicistat is not mentioned in the US PI. This checker reflects the more cautious option.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin. Bamlanivimab and etesevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin. Baricitinib does not inhibit these pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of a dose of bezafibrate is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely. [Note, the European SmPC for bezafibrate contraindicates its use in significant hepatic disease.]

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other products containing tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European product label for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment whereas the US Prescribing Information recommends an initial 2.5 mg in hepatic impairment with caution in further dose titration.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction Is unlikely. Black cohosh does not appear to be a potent modulator of human drug metabolism. Standardized black cohosh supplements, when taken at recommended doses, pose little risk for herb-drug interactions. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. 

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. Unlike cidofovir, brincidofovir is not a substrate of OATs and therefore is less likely to accumulate in the kidney thereby reducing the potential for nephrotoxicity. Furthermore, the administration of oral brincidofovir leads to cidofovir plasma concentrations <1% of those observed after IV cidofovir. Brincidofovir is an inhibitor of BCRP but not of P-gp, and therefore could increase tenofovir alafenamide although to an extent that would not warrant a dose adjustment of tenofovir alafenamide. Tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1 such as brincidofovir may affect the distribution of tenofovir alafenamide in the body.

Coadministration has not been formally studied but based on current knowledge of the effect of vaccines on drug disposition a clinically significant interaction is considered unlikely.

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of oral rilpivirine (25 mg once daily) and tenofovir alafenamide (25 mg once daily) had no significant effect on the pharmacokinetics of rilpivirine (AUC and Cmin increased by 1% and 13%, Cmax decreased by 7%). Tenofovir alafenamide Cmax and AUC were unchanged. Tenofovir Cmax, AUC and Cmin increased by 13%, 11% and 18%, respectively. No dose adjustment of tenofovir alafenamide or oral rilpivirine is required. Similarly, no dose adjustment is needed with intramuscular rilpivirine and cabotegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely. [Note, use of candesartan in severe hepatic impairment is contraindicated in the European SmPC; the US Prescribing Information recommends caution in moderate hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Tenofovir alafenamide does not interfere with these pathways.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleotide analogues such as tenofovir alafenamide may compete for these metabolic pathways. The clinical relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely.

Coadministration is not recommended as it decreases tenofovir alafenamide plasma concentrations which may result in loss of therapeutic effect and development of resistance. Coadministration of carbamazepine (titrated from 100 mg to 300 mg twice a day) with emtricitabine/tenofovir alafenamide (200/25 mg once daily) decreased tenofovir alafenamide AUC and Cmax by 55% and 57%, respectively. Coadministration is not recommended in the European SmPC but the US PI recommends increasing the tenofovir alafenamide dose to two tablets once daily. This checker reflects the more cautious option.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Carfentanil is expected to be metabolized by CYP3A4/5. Tenofovir alafenamide does not interact with this pathway. However, carfentanil is an extremely strong opiate, reported to be up to 10,000 times more potent than morphine, and multiple deaths have resulted from its use. Advise patients to avoid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP or other hepatic metabolism described. [Note, the US Prescribing Information contraindicates carvedilol in patients with severe liver impairment and the European SmPC contraindicates it in patients with hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir alafenamide is metabolized to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin. Casirivimab and imdevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Casirivimab and imdevimab are not renally excreted. Interactions with concomitant medications that are renally excreted are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non-CYP-mediated pathway. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no other hepatic metabolism described. [Note, no dose adjustment is required in patients with normal hepatic function but a dose reduction of caspofungin daily dose to 35 mg is recommended for adults with moderate hepatic impairment. There is no clinical experience in adults with severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw is a CYP3A4 inhibitor. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolised by CYP2C9. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. [Note, use in patients with severe liver impairment is contraindicated in the European SmPC and not recommended in the US Prescribing Information. In patients with moderate liver impairment (serum albumin 25-35 g/L, Child-Pugh Class B), celecoxib treatment should be started at half the recommended dose.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is a substrate of CYPs 2D6 (major), 1A2, and 3A4 in vitro. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European SmPC for chlorpromazine advises that its use should be avoided in patients with hepatic dysfunction.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorprothixene is metabolised by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, although no interaction is anticipated, ECG monitoring is mandatory prior to treatment with chlorprothixene.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Tenofovir alafenamide is unlikely to compete with cidofovir for renal transporters or to be of concern when coadministered with nephrotoxic agents such as cidofovir as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely. [Note, in patients with cirrhosis, a maximum dose of 0.5 mg/day is recommended as significant hypotension may occur.]

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Tenofovir alafenamide does not affect this pathway. [Note, the US Prescribing Information for clofazimine recommends to avoid clofazimine in patients with hepatic impairment (Child-Pugh Class A, B, and C) unless the benefit outweighs the risk.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European SmPC for clopidogrel contraindicates its use in severe hepatic impairment but the US Prescribing Information states no dose alteration.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolised by several pathways (CYP- and non-CYP-mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of conjugated estrogens is complex and involves CYP3A4 isoenzymes and glucuronidation in the liver. These pathways are not affected by tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolised by several pathways (CYP- and non-CYP-mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methamphetamine is mainly metabolised by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Tenofovir alafenamide is not expected to interact with these pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is metabolised by CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. No dose adjustment of daclatasvir is required. However, tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1/B3 such as daclatasvir may affect the distribution of tenofovir alafenamide in the body 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. Danaparoid is renally excreted by unknown mechanisms. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely.

Coadministration is not recommended. Coadministration of darunavir/ritonavir (800/100 mg once daily) and tenofovir alafenamide (10 mg once daily) increased tenofovir AUC and Cmax by 105% and 142%, respectively. No significant effects were observed on darunavir pharmacokinetics. The European SmPC states that coadministration is not recommended but darunavir/ritonavir is not mentioned in the US PI. This checker reflects the more cautious option.

Symtuza (darunavir, cobicistat, emtricatabine, tenofovir alafenamide) contains tenofovir alafenamide and must not be administered with other products containing tenofovir alafenamide.

Coadministration with tenofovir alafenamide alone has not been studied and is not recommended. Coadministration with darunavir/cobicistat (800/150 mg once daily) and emtricitabine/tenofovir alafenamide (200/25 mg once daily) increased tenofovir AUC and Cmax by 224% and 216%, respectively. No significant effects were observed on darunavir pharmacokinetics. The European SmPC states that coadministration is not recommended but darunavir/cobicistat is not mentioned in the US PI. This checker reflects the more cautious option.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, delamanid is not recommended in patients with moderate to severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is not anticipated and contraceptive efficacy is unlikely to be affected. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Desogestrel is a prodrug that requires activation to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. These pathways are not affected by tenofovir alafenamide. No clinically significant drug interactions were observed when tenofovir alafenamide (25 mg once daily, as emtricitabine/tenofovir alafenamide fixed-dose combination tablet) was coadministered with oral contraceptives (ethinylestradiol/norgestimate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is not anticipated and contraceptive efficacy is unlikely to be affected. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Desogestrel is a prodrug that requires activation to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. These pathways are not affected by tenofovir alafenamide. No clinically significant drug interactions were observed when tenofovir alafenamide (25 mg once daily, as emtricitabine/tenofovir alafenamide fixed-dose combination tablet) was coadministered with oral contraceptives (ethinylestradiol/norgestimate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is a substrate of CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolised mainly in the liver but also in the kidney. Dexamethasone and its metabolites are excreted in the urine. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. Dexamethasone induces intestinal P-glycoprotein and could reduce the absorption of tenofovir alafenamide, although to a moderate extent. No a priori dose adjustment of tenofovir alafenamide is needed as coadministration with rifampicin (a stronger inducer) led to lower intracellular tenofovir diphosphate concentrations but which were still higher than those achieved with tenofovir disoproxil fumarate.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly glucuronidated, with CYP mediated metabolism (CYP2C8/9) playing a minor role. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. [Note, use in patients with severe hepatic impairment (Child-Pugh class C) is contraindicated in the European product label for dexketoprofen.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied. Increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF. A similar effect with tenofovir alafenamide cannot be excluded. If this combination is judged strictly necessary, patients should be carefully monitored for efficacy and didanosine related adverse events.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, diphenhydramine should be used with caution in patients with moderate to severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dofetilide is mainly excreted unchanged in urine. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely.

Coadministration of dolutegravir (50 mg once daily) and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (10/200/150/150 mg) had no significant effect on the pharmacokinetics of dolutegravir and tenofovir alafenamide. The recommended dose of tenofovir alafenamide is 25 mg once daily.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Coadministration of rilpivirine (25 mg once daily) and tenofovir alafenamide (25 mg once daily) had no significant effect on the pharmacokinetics of tenofovir, tenofovir alafenamide or rilpivirine. Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg once daily) had no significant effect on the pharmacokinetics of tenofovir, tenofovir alafenamide or dolutegravir. If given with dolutegravir or rilpivirine, the recommended dose of tenofovir alafenamide is 25 mg once daily. Note, Juluca (dolutegravir/rilpivirine) is is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with products also for the treatment of HIV.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Tenofovir alafenamide does not interfere with CYP450 mediated metabolism.

Delstrigo (doravirine, lamivudine, and tenofovir-DF) contains tenofovir-DF and should not be administered with tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dosulepin is extensively metabolised in the liver, likely by CYP2D6 (major) and CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note: Dosulepin should be used with caution in mild to moderate hepatic impairment and avoided in severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolised mainly by CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European SmPC does not recommend doxazosin in severe hepatic impairment; the US Prescribing Information has a caution for use in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolised to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolised by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European and US product labels for doxepin advise caution and monitoring in patients with hepatic impairment as a dosage reduction may be required.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolized primarily by CYP2D6, CYP1A2, and CYP2C9. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronedarone is metabolised by CYP3A4, Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. Tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1/B3 such as dronedarone may affect the distribution of tenofovir alafenamide in the body , 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. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Drospirenone is metabolised in part by CYP3A4. These pathways are not affected by tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely and contraceptive efficacy is unlikely to be affected. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Drospirenone is metabolised in part by CYP3A4. These pathways are not affected by tenofovir alafenamide. No clinically significant drug interactions were observed when tenofovir alafenamide (25 mg once daily, as emtricitabine/tenofovir alafenamide fixed-dose combination tablet) was coadministered with oral contraceptives (ethinylestradiol/norgestimate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely and contraceptive efficacy is unlikely to be affected. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Drospirenone is metabolised in part by CYP3A4. These pathways are not affected by tenofovir alafenamide. No clinically significant drug interactions were observed when tenofovir alafenamide (25 mg once daily, as emtricitabine/tenofovir alafenamide fixed-dose combination tablet) was coadministered with oral contraceptives (ethinylestradiol/norgestimate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolised by CYP2D6 and CYP1A2. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, duloxetine is contraindicated in patients with hepatic impairment as concentrations may increase due to decreased clearance of duloxetine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolised by CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described. [Note, the European SmPC (but not the US Prescribing Information) cautions against dutasteride use in mild to moderate hepatic impairment and contraindicates it in severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). These pathways are not affected by tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolised mainly by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Coadministration of efavirenz (600 mg once daily) and tenofovir alafenamide (40 mg once daily, dosed with emtricitabine) decreased tenofovir alafenamide AUC and Cmax by 14% and 22%, respectively. The recommended dose of tenofovir alafenamide is 25 mg once daily.

Coadministration has not been studied. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP or other hepatic metabolism described. Tenofovir alafenamide enters hepatocytes via OATP1B1/B3 and inhibitors of OATP1B1 such as eltrombopag may affect the distribution of tenofovir alafenamide in the body, but this is unlikely to be clinically relevant.

Genvoya (elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other products containing tenofovir alafenamide.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with products containing tenofovir alafenamide.

Tenofovir alafenamide should not be administered with additional tenofovir.

Emtricitabine/tenofovir-DF contains tenofovir-DF and should not be administered with tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. [Note, due to the possible risk of hepatitis B (HBV) reactivation, patients should be tested for HBV infection before initiating treatment with etanercept. Patients who test positive for HBV infection should be discussed with a physician with expertise in the treatment of HBV.]