Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on abacavir AUC but Cmax increased by 12%. A similar increase in abacavir Cmax may occur with emtricitabine/tenofovir-DF. 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. A similar outcome is anticipated if emtricitabine/tenofovir-DF is combined with a third NRTI.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolized by CYP3A4. Emtricitabine or tenofovir-DF do not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Emtricitabine and tenofovir-DF do 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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (exact transporter unknown, possibly OATs or OCTs). Given the potential limited role of OCT or OAT in acamprosate’s elimination and considering the therapeutic index of acamprosate, no clinically relevant interaction with tenofovir is anticipated. However, acamprosate and emtricitabine may compete for tubular secretion, which could lead to increased concentrations of either drug. 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. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as acenocoumarol is mainly metabolized by CYP2C9.

Coadministration has not been studied. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. No interaction is expected with emtricitabine as emtricitabine and acetazolamide are eliminated by different renal transporters. However in vitro studies have shown acetazolamide may competitively inhibit the renal transporters OAT1, OAT3 and OAT4. Tenofovir is mainly eliminated by OAT1 (and to a lesser extent by OAT3) and concentrations of tenofovir may increase. Close monitoring of renal function is recommended.

Coadministration has not been studied. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. No interaction is expected with emtricitabine as emtricitabine and aciclovir are eliminated by different renal transporters. However, an increase in tenofovir or aciclovir concentrations may occur due to reduced renal function or competition for active tubular secretion.

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

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

Coadministration has not been studied. 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 emtricitabine/tenofovir-DF should be separated by 4 hours. [Note: this interaction is not specific for emtricitabine/tenofovir-DF, but for any oral medication taken with activated charcoal.]

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.

Emtricitabine/tenofovir-DF and adefovir dipivoxil should not be coadministered. Coadministration of adefovir dipivoxil and tenofovir-DF decreased adefovir AUC and Cmax by 11% and 7%; tenofovir AUC and Cmax decreased by 2% and 1%.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). There is little potential for an interaction with emtricitabine and tenofovir via modulation of, or competition for, metabolic or elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Afatinib is mainly eliminated unchanged in the faeces. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism clearance a clinically significant interaction is unlikely. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. No interaction is expected with emtricitabine Tenofovir-DF (the prodrug of tenofovir) is a substrate of P-gp, however, rifampicin (a P-gp inducer) had no significant effect on tenofovir and no interaction is expected with African potato.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly by CYP1A2.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system. There is little potential for an interaction with emtricitabine and tenofovir due to competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance, as well as limited drug-drug interaction data, a clinically significant interaction is unlikely. Emtricitabine and tenofovir are eliminated renally. An interaction is unlikely as albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase.

Coadministration has not been studied. Alcuronium is predominantly excreted unchanged by the kidneys. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is some potential for competition with emtricitabine and tenofovir for active renal transport mechanisms, which may lead to increased levels of either drug.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alfentanil undergoes extensive CYP3A4 metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alfuzosin is metabolized mainly by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. P-glycoprotein is a major determinant of aliskiren bioavailability.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Furthermore, alogliptin was shown to be neither a substrate nor an inhibitor of the renal transporters OAT1, OAT3 or OCT2 and to cause no interactions with P-glycoprotein substrates.

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

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. Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alprazolam is metabolized mainly by CYP3A4.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. Emtricitabine and tenofovir are unlikely to interfere with amantadine renal elimination as they are eliminated by different renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Emtricitabine/tenofovir-DF does not interfere with ambrisentan metabolism.

Coadministration has not been studied. Amikacin is eliminated by glomerular filtration therefore no pharmacokinetic interaction is expected. However, use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amiloride is eliminated unchanged by the kidney. In vitro data indicate that amiloride is a substrate of OCT2 and an interaction is unlikely as emtricitabine and tenofovir are eliminated by other renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2.

Coadministration has not been studied. A clinically significant effect on amiodarone is unlikely as it is metabolised by CYP3A4 and amiodarone is unlikely to affect concentrations of emtricitabine. However, amiodarone is an inhibitor of P-gp and could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentrations of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amitriptyline is metabolized predominantly by CYP2D6 and CYP2C19.

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. Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amlodipine is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amodiaquine is mainly metabolized by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly eliminated unchanged in the kidney and in vitro data indicate that it is a substrate of OAT3. Emtricitabine is not eliminated by OAT3 and this renal transporter plays a secondary role in tenofovir elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolized by CYP2D6.

Coadministration has not been studied. Based on metabolism and clearance, a pharmacokinetic interaction is unlikely. However, use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product (such as amphotericin B). If concomitant use of emtricitabine/tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be closely monitored.

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion with ~20-40% of an oral dose and ~60-80% of a parenteral dose being excreted in the urine in 6 hours. As emtricitabine and tenofovir are eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased levels of either drug when ampicillin is administered intravenously. There is little potential for a significant interaction with orally administered ampicillin.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4. Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Apremilast has no inhibitory or inducing effects or drug transporters. Emtricitabine or tenofovir-DF do not interact with apremilast’s elimination pathways. 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. Emtricitabine and tenofovir (derived from tenofovir -DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as aripiprazole is metabolized by CYP3A4 and CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Arsenic trioxide is hydrolysed to arsenious acid (the pharmacologically active metabolite) which is then methylated to less cytotoxic metabolites primarily in the liver (non-CYP mediated). Arsenious acid is also oxidated to arsenic acid, which may occur in numerous tissues via enzymatic or nonenzymatic processes. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolized via UGTs 1A9 and 2B7.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. Emtricitabine and tenofovir-DF are predominantly eliminated unchanged via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected.

Coadministration has not been studied. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. Emtricitabine and tenofovir-DF are predominantly eliminated unchanged via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected with vitamin C when given alone or in multivitamins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial system. Less than 0.1% of a total injected dose is recovered in urine.

Coadministration has not been studied. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). However, coadministration could potentially result in increased risk of nephrotoxicity. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. The risk is increased if an NSAID is used for a long duration, if the patient has pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If emtricitabine/tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately.

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). Aspirin used as an antiplatelet agent at 100 mg once daily in chronic use is unlikely to increase the risk of tenofovir-DF nephrotoxicity.  

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as astemizole is metabolized by CYPs 2D6, 2J2 and 3A4.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir/ritonavir (300/100 mg once daily) was studied in 12 subjects. Atazanavir AUC, Cmax and Cmin decreased by 25%, 28% and 26%, respectively. Tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir associated adverse events, including renal disorders. Renal function should be closely monitored. In HIV-1 infected patients with renal risk factors, the co-administration of tenofovir-DF with a boosted protease inhibitor should be carefully evaluated.

Coadministration has not been studied and is not recommended. The US product label for emtricitabine/tenofovir-DF states that atazanavir should not be given alone with emtricitabine/tenofovir-DF, but should be administered at a dose of 300 mg once daily with ritonavir 100 mg once daily. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir alone (400 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively (n=34); tenofovir AUC, Cmax and Cmin increased by 24%, 14% and 22%, respectively (n=33).

Coadministration with emtricitabine/tenofovir-DF has not been studied. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir/ritonavir (300/100 mg once daily) was studied in 12 subjects. Atazanavir AUC, Cmax and Cmin decreased by 25%, 28% and 26%, respectively. Tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir associated adverse events, including renal disorders. Renal function should be closely monitored. In HIV-1 infected patients with renal risk factors, the co-administration of tenofovir-DF with a boosted protease inhibitor should be carefully evaluated. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir/cobicistat should not be coadministered with emtricitabine or tenofovir-DF in patients with creatinine clearance less than 70 ml/min.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolized by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atorvastatin is metabolized by CYP3A4.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when atropine is used either systemically or as eye drops. Up to 50% of a dose is excreted unchanged via the kidneys. There is low potential for clinically significant interactions with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avanafil is primarily metabolized by CYP3A4. 

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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

Coadministration has not been studied. 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. Phosphorylation of emtricitabine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. No interaction is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is metabolized to 6-mercaptopurine which is further inactivated by xanthine oxidase and thiopurine methyltransferase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as azithromycin is mainly eliminated via biliary excretion.

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

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally. Baricitinib does not inhibit renal transporters.

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

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Emtricitabine and tenofovir-DF do not interact with these metabolic pathways.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. There are no clinical data on the safety and efficacy of bedaquiline when coadministered with antiretroviral agents.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically relevant drug interaction is unlikely in the range of observed clinical concentrations.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways. A case study of a patient taking an antiretroviral regimen of tenofovir-DF, emtricitabine and raltegravir reported no clinical or laboratory adverse events when the patient received benznidazole 5 mg/kg daily for 90 days. At the end of treatment, the patient’s viral load remained undetectable, and CD4 count was maintained.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benzonatate is metabolized by plasma butyrylcholinesterase. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bepridil is mainly metabolized by CYP2D6 and to a lesser extent by CYP3A4.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4.

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 as betrixaban is largely eliminated unchanged through biliary secretion via P-gp.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bexarotene is mainly metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Emtricitabine is excreted by different renal transporters and a clinically relevant effect on tenofovir is unlikely in the observed range of clinical concentrations.

Coadministration has not been studied. Bicalutamide is metabolized by CYP3A4 and UGT1A9. No interaction is expected with emtricitabine which is eliminated renally. Bicalutamide is a weak inhibitor of P-gp in vitro and could potentially increase the absorption of tenofovir-DF (the prodrug of tenofovir) although to a limited extent.

Biktarvy (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. Furthermore, Biktarvy contains tenofovir alafenamide and emtricitabine and should not be administered with tenofovir-DF or additional emtricitabine (both components of Truvada).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

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

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

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally. Significant interactions are not expected with emtricitabine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. In vitro data indicate that bisoprolol inhibits OCT2, however a clinically relevant interaction with emtricitabine or tenofovir is unlikely as these drugs are eliminated by different renal transporters.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect on tenofovir-DF (the prodrug of tenofovir) is expected as black cohosh had no significant effect on the pharmacokinetics of digoxin (a P-gp substrate).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolic pathway of blinatumomab has not been characterized. 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 clinically significant interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and CYP2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bosentan is metabolized by CYP3A4 and CYP2C9.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this pathway.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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 emtricitabine/tenofovir-DF. MMAE is a substrate of CYP3A4 and P-gp but emtricitabine/tenofovir-DF does not interfere with these pathways.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brigatinib is metabolised by CYP2C8 and CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. No interaction is expected with emtricitabine. Unlike cidofovir, brincidofovir is not a substrate of OATs and is less likely to accumulate in the kidney thereby reducing the potential for nephrotoxicity. Furthermore, administration of oral brincidofovir leads to cidofovir plasma concentrations less than 1% of those observed after IV cidofovir. Tenofovir is primarily eliminated by the kidneys, notably via OAT1, however given that brincidofovir is not a substrate of this transporter no pharmacokinetic interaction is expected. In addition, the potential risk of nephrotoxicity with tenofovir-DF is expected to be lower with brincidofovir given that it results in lower cidofovir concentrations. Brincidofovir inhibits BCRP but not P-gp and therefore could increase tenofovir-DF exposure although to a limited extent.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bromazepam undergoes oxidative biotransformation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as budesonide is metabolized by CYP3A4.

Coadministration has not been studied. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). In vitro data suggest that bumetanide inhibits OAT1. No interaction is expected with emtricitabine as it is eliminated by other renal transporters. However, coadministration is expected to affect tenofovir renal elimination and increase the risk of renal toxicity. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal excretion of unchanged bupivacaine is ~1% of a dose and there is little potential for an interaction with emtricitabine and tenofovir due to competition for renal elimination pathways.

Coadministration with emtricitabine/tenofovir-DF has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Coadministration of buprenorphine and tenofovir-DF was investigated in 10 HIV-negative, buprenorphine/naloxone maintained subjects. When compared to values obtained from control subjects not receiving buprenorphine, no significant changes in buprenorphine pharmacokinetics were observed. When compared to controls, buprenorphine had no statistically significant effect on NRTI concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bupropion is primarily metabolized by CYP2B6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as buspirone is metabolized by CYP3A4.

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). Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism).

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

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 emtricitabine and tenofovir-DF would be possible from a pharmacokinetic standpoint. Coadministration with cabotegravir LA or rilpivirine LA has not been studied. Coadministration of oral rilpivirine (150 mg once daily) and tenofovir-DF (300 mg once daily) decreased rilpivirine Cmax and Cmin by 4% and 1%, and increased AUC by 1%. Tenofovir Cmax, AUC and Cmin increased by 19%, 23% and 24%. No dose adjustment is necessary. 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 clinically significant interaction is unlikely. Cabozantinib is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as caffeine is mainly metabolized by CYP1A2.

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. Emtricitabine and tenofovir-DF do not interfere with this pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcium is eliminated through faeces, urine and sweat.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 which are not affected by emtricitabine/tenofovir-DF. However, since an increased risk for bone fractures has been reported with canagliflozin (particularly in patients with a history of, or at high risk of, cardiovascular disease), caution is recommended when coadministering canagliflozin in the long term with tenofovir-DF due to potential additive bone toxicities.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. THC, the principal psychoactive constituent of cannabis, is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleoside/tide analogues such as emtricitabine and tenofovir-DF 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. Capmatinib is primarily metabolized by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Capreomycin is predominantly excreted in the urine as unchanged drug, and therefore may potentially compete with emtricitabine and tenofovir for renal elimination transport mechanisms resulting in increased concentrations of either drug. Renal toxicity has been reported during capreomycin treatment and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of emtricitabine/tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1 but emtricitabine is excreted by different renal transporters. An interaction with tenofovir via competition for OAT1 is unlikely to be of clinical significance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbamazepine is almost completely metabolized in the liver to carbamazepine 10,11 epoxide. No interaction is expected with emtricitabine, but carbamazepine is an inducer of P-gp and therefore could reduce the absorption of tenofovir-DF. Based on the results of the interaction study between tenofovir-DF and rifampicin (another inducer of P-gp) carbamazepine would be expected to cause only a small decrease in tenofovir-DF. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (also known as methimazole).

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Carboplatin is excreted primarily by renal glomerular filtration and there is little potential for competition for active renal elimination mechanisms by carboplatin, emtricitabine and tenofovir. However carboplatin has nephrotoxic potential and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. No interaction is expected as emtricitabine and tenofovir-DF do not undergo CYP3A4 metabolism.

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). Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. A clinically significant interaction due to competition for MATE1 is unlikely with emtricitabine as it has a wide safety margin. However, there is potential competition for OAT1 between cefalexin and tenofovir, which could lead to increased concentrations of either drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. OAT3 does not play a major role in the renal elimination of emtricitabine and tenofovir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. As cefixime is renally excreted predominantly by glomerular filtration, with no significant active renal tubular secretion, there is little potential for an interaction with emtricitabine and tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolized by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime whereas emtricitabine and tenofovir are eliminated by other renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. As ceftazidime is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion, there is little potential for an interaction with emtricitabine and tenofovir via competition for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. As ceftriaxone is excreted predominantly by renal glomerular filtration with minimal active renal tubular secretion, there is little potential for an interaction with emtricitabine and tenofovir via competition for active renal transport mechanisms.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as celecoxib is metabolised mainly by CYP2C9. However, coadministration could potentially result in increased risk of nephrotoxicity. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If emtricitabine/tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Cenobamate inhibits OAT3 but this does not impact emtricitabine elimination. Tenofovir is mainly eliminated by OAT1 and to a lesser extent by OAT3. Inhibition of OAT3 by cenobamate could potentially increase tenofovir exposure, although to a limited extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceritinib is metabolized by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. In vitro data indicate that cetirizine inhibits OCT2 but this is not involved in the renal elimination of emtricitabine or tenofovir.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolised via UDP-glucuronyltransferases, in particular UGT2B7.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolized by hepatic microsomal enzymes.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Ethinylestradiol is also metabolized by hydroxylation and glucuronidation. Emtricitabine and tenofovir-DF do not interact with these metabolic pathways.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized via CYP2D6 and approximately 22% of a chlorphenamine dose is excreted unchanged in the urine. There is little potential for an interaction with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also CYP1A2.

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

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

Coadministration has not been studied.  A clinically significant effect on ciclosporin is unlikely as it is mainly metabolized by CYP3A4 and no interaction is expected with emtricitabine. However, ciclosporin is an inhibitor of P-gp and could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended, especially as ciclosporin can also impair renal function. 

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely with emtricitabine as cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Since tenofovir is primarily eliminated by the kidneys, coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir or the coadministered drug. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 at concentrations much higher than observed clinical concentrations. No interaction is expected with emtricitabine or tenofovir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolized and partially cleared through the bile and intestine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cisapride is metabolised mainly by CYP3A4.

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

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1: cisplatin and emtricitabine could potentially compete for MATE1, slowing their elimination. Based on metabolism and clearance a pharmacokinetic interaction is unlikely with tenofovir as it is eliminated by other renal transporters, however, coadministration may increase the risk of nephrotoxicity. If coadministration of emtricitabine/tenofovir-DF and cisplatin is necessary, close monitoring of renal function is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%).

Coadministration has not been studied. A clinically significant effect on clarithromycin is unlikely as it is mainly metabolized by CYP3A4 and clarithromycin is unlikely to affect emtricitabine concentrations. However, clarithromycin is an inhibitor of P-gp and could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is extensively metabolised in the liver but the enzymes responsible are undefined. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4 with some metabolites having antibacterial activity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. As renal excretion has a minor role in clofazimine elimination, an interaction with emtricitabine and tenofovir via competition for renal elimination pathways is unlikely.

Coadministration has not been studied. Clofibrate is metabolised mainly to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. OAT1 does not participate in emtricitabine renal excretion. No clinically significant increases in clofibrate or tenofovir are anticipated as a result of competition for renal secretion via OAT1. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal excretion of clomifene is thought to account for approximately 8% of an oral dose. There is little potential for an interaction with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). Clonidine is a weak inhibitor of OCT2 but is unlikely to affect emtricitabine or tenofovir which are eliminated by different renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted via renal glomerular filtration and tubular secretion. As total renal elimination is approximately 35% of a dose, there is little potential for significant interactions with emtricitabine and tenofovir via competition for renal transport.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolized by several pathways (non-CYP and CYP-mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine undergoes predominantly direct glucuronidation with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism.

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. Emtricitabine and tenofovir-DF are eliminated renally. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as colchicine is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for an interaction with emtricitabine and tenofovir-DF via modulation of, or competition for, metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with vitamin D when given with calcium or in a multivitamin preparation. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for interaction with emtricitabine/tenofovir-DF via modulation of, or competition for, metabolic pathways.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Emtricitabine and tenofovir-DF are eliminated renally. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after emtricitabine/tenofovir-DF 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 emtricitabine and tenofovir-DF, 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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Emtricitabine and tenofovir-DF do not interact with these metabolic pathways. In addition, no interaction is expected with progestogens administered as part of HRT. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

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%). Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Crizotinib is mainly metabolized by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely with emtricitabine. However, piperine, a component of Piper cubeba, inhibits intestinal P-gp and could potentially increase absorption of tenofovir-DF, thereby increasing tenofovir systemic concentrations. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with cyanocobalamin when given alone or in multivitamins. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration and there is little potential for an interaction with emtricitabine and tenofovir via competition for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cytarabine is metabolized by cytidine deaminase.

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. Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is not metabolized by CYP450 isoenzymes and is mainly cleared by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely as dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. However, in vitro data suggest that dacarbazine is a substrate of the renal transporter OAT1 and concentrations of tenofovir and dacarbazine could be increased due to competition for active tubular secretion. No a priori dosage adjustment is recommended but renal function and haematological parameters should be monitored.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of tenofovir-DF (300 mg once daily) and daclatasvir (60 mg once daily) had no clinically relevant effect on daclatasvir AUC, Cmax or Cmin (increases of 10%, 6% and 15%, respectively). There was no clinically relevant effect on tenofovir AUC (10% increase), Cmax (5% decrease) or Cmin (17% increase). No dose adjustment of daclatasvir or emtricitabine/tenofovir-DF is required.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolized, is concentrated in nucleated cells, and does not penetrate the blood-brain barrier.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Emtricitabine and tenofovir-DF are eliminated renally. 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. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daridorexant is mainly metabolised by CYP3A4. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Emtricitabine and tenofovir-DF are eliminated renally.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely with emtricitabine as it is primarily renally excreted and darunavir/ritonavir is unlikely to inhibit OCTs at clinically relevant concentrations. Coadministration of tenofovir-DF (300 mg once daily) and darunavir/ritonavir (300/100 mg twice daily, a dose lower than that licensed) increased darunavir Cmax (16%), AUC (21%) and Cmin (24%). Tenofovir Cmax, AUC and Cmin increased by 24%, 22% and 37%, respectively. No adjustments to the licensed doses are required. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir or cobicistat boosted protease inhibitor. Close monitoring of renal function and for tenofovir-associated adverse reactions is required in these patients.

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. Furthermore, Symtuza contains emtricitabine and tenofovir alafenamide must not be administered with other products containing emtricitabine, or with tenofovir-DF.

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely with emtricitabine as it is primarily renally excreted and darunavir/cobicistat is unlikely to inhibit OCTs at clinically relevant concentrations. However, darunavir/cobicistat is expected to increase tenofovir plasma concentrations (inhibition of P-gp). Darunavir/cobicistat and tenofovir disoproxil fumarate can be used without dose adjustments, but monitoring of renal function may be indicated when darunavir/cobicistat is given in combination with tenofovir disoproxil fumarate, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is metabolized by CYP3A4.

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

Coadministration has not been studied. 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. Phosphorylation of emtricitabine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. No interaction is expected with tenofovir-DF.

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%). Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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%). Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir-DF do not affect CYP enzymes.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as desipramine is metabolized by CYP2D6.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. No clinically significant drug interactions were observed when tenofovir-DF was coadministered with a COC containing ethinylestradiol/norgestimate.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolized by CYP3A4. Dexamethasone and its metabolites are excreted in the urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolized by CYP3A4. Dexamethasone and its metabolites are excreted in the urine.

Coadministration has not been studied. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally. No interaction is expected with emtricitabine. However, renal elimination of tenofovir-DF could potentially decrease, thereby increasing the risk of nephrotoxicity. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexlansoprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly CYP2A6).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dextropropoxyphene is mainly metabolized by CYP3A4.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYPs 3A4 and 2C19) and to temazepam (mainly by CYP3A4).

Coadministration with emtricitabine has not been studied. Based on metabolism and clearance a clinically significant interaction is unlikely as diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. However, diclofenac could potentially decrease renal elimination of tenofovir (thereby increasing the risk of nephrotoxicity) as diclofenac is a strong inhibitor of MRP4. A retrospective analysis showed that patients treated with diclofenac together with tenofovir-DF containing regimens were at higher risk of developing an acute kidney injury when compared to patients treated with tenofovir-DF-sparing regimens. Since diclofenac can exacerbate tenofovir-DF nephrotoxicity, diclofenac should be used with caution with emtricitabine/tenofovir-DF and close monitoring of renal function is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as digoxin is eliminated renally via the renal transporters OATP4C1 and P-glycoprotein. Emtricitabine and tenofovir are excreted by different renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dihydroergotamine is metabolized by CYP3A4.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diltiazem is metabolized by CYP3A4 and CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Emtricitabine and tenofovir-DF are eliminated renally. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp. However, coadministration with tenofovir-DF may increase the risk of nephrotoxicity. If concomitant use of tenofovir-DF and dimethyl fumarate is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily.

Coadministration has not been studied but based on metabolism and elimination a clinically significant interaction is unlikely.  Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. In vitro data suggest that disopyramide inhibits the renal transporter OCT2 in rats, but no drug interaction is expected as OCT2 does not contribute to the renal excretion of emtricitabine or tenofovir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as docetaxel is metabolized by CYP3A4.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%).

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and elimination a clinically significant interaction with emtricitabine is unlikely. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. Coadministration with emtricitabine has not been studied but based on metabolism and elimination no clinically significant interaction is likely. No dosage adjustment is necessary.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection. Products containing lamivudine should not be taken with products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, both products contain tenofovir-DF and should not be coadministered with additional tenofovir-DF.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Triumeq contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with emtricitabine/tenofovir-DF would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as domperidone is mainly metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal elimination of unchanged dopamine is minimal. There is little potential for an interaction with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interfere with CYP450 mediated metabolism.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and tenofovir-DF and should not be administered products containing emtricitabine or additional tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as doxazosin is metabolized mainly by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized mainly by CYP2C19 to nordoxepin, an active metabolite. In addition, doxepin and nordoxepin are metabolized by CYP2D6.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance (40- 60% of an administered dose can be accounted for in the urine). Studies indicate that administration of doxycycline at the recommended doses does not lead to excessive accumulation in patients with renal impairment. There is therefore little potential for a clinically significant interaction with emtricitabine and tenofovir via competition for renal elimination transport mechanisms.

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. Emtricitabine and tenofovir (derived from tenofovir-DF) are eliminated renally.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronedarone is primarily metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interfere with this metabolic pathway.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Emtricitabine/tenofovir-DF does not interact with these metabolic pathways. No clinically significant drug interactions were observed when tenofovir-DF was coadministered with a COC containing ethinylestradiol/norgestimate.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Emtricitabine/tenofovir-DF does not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.