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. 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 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 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. 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. 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 as alprazolam is metabolized mainly by CYP3A4.

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 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. 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. 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. 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. 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. 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. 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 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 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 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 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. 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. Basiliximab 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. 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. 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. 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. 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 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. 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 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.

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 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. 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. 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 as bromazepam undergoes oxidative biotransformation.

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 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 as caffeine is mainly metabolized by CYP1A2.

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 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. 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. 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. 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. 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. 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. 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 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. 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. 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. 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 as colchicine is metabolized by CYP3A4.

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. 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 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. 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. Dabigatran is not metabolized by CYP450 isoenzymes and is mainly cleared by glomerular filtration.

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. 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. 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. Darifenacin is metabolized by CYP3A4 and CYP2D6.

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. 

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 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.

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 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 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. 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 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 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 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.

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. 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 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 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.

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

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

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

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). 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.

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. MDMA is metabolized mainly by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%). Edoxaban is eliminated primarily as unchanged drug in urine.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of emtricitabine and efavirenz in the presence of didanosine was studied in 9 treatment naive, HIV+ patients. When compared to historical data for each drug alone, the pharmacokinetics of emtricitabine were not affected, didanosine AUC and Cmax were higher than expected and efavirenz Cmax, Cmin and AUC were lower than expected. However, efavirenz concentrations may have been underestimated as dosing was delayed by 12 hours for ease of sampling. Coadministration of tenofovir-DF and efavirenz decreased efavirenz AUC and Cmax both by 4%; tenofovir AUC decreased by 1% and Cmax increased by 7%. No dosage adjustment of efavirenz is necessary.

Coadministration has not been studied. Approximately 80% of oral/intravenous doses of eflornithine are excreted unchanged via the kidneys. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is potential for competition with emtricitabine and tenofovir for active renal transport mechanisms, which may lead to increased levels of either drug. A clinically significant interaction is not expected with topical preparations as less than 1% of topically applied eflornithine is systemically absorbed.

Coadministration with emtricitabine/tenofovir-DF alone has not been studied. No clinically significant interaction is expected with emtricitabine. There was no clinically significant effect on tenofovir pharmacokinetics when administered with elbasvir (tenofovir AUC, Cmax, Ctrough increased by 34%, 47%, 29%), grazoprevir (tenofovir AUC, Cmax, Ctrough increased by 18%, 14%, 24%) or elbasvir/grazoprevir (tenofovir AUC, Cmax and Ctrough increased by 27%, 14% and ~20%). Tenofovir-DF had no clinically significant effect on elbasvir (AUC, Cmax, C24 decreased by 7%, 12%, 8%) or grazoprevir (AUC, Cmax, C24 decreased by 14%, 22%, 11%). No dose adjustments are required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (UGTs 1A1 and 1A3) and oxidation (CYPs 1A2 and 2C8).

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Genvoya contains tenofovir alafenamide and emtricitabine and should not be administered with tenofovir-DF or additional emtricitabine (both components of Truvada).

Stribild (elvitegravir, cobicistat, emtricitabine, 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, it must not be administered with other products containing emtricitabine and tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3, but there is little potential for an interaction via competition for these transporters.

Emtricitabine/tenofovir-DF (Truvada) is a fixed dose combination and should not be administered with additional emtricitabine.

Emtricitabine/tenofovir-DF should not be administered with additional emtricitabine or with tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally, possibly via OATs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as enflurane is predominantly metabolized by CYP2E1.

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

Coadministration with emtricitabine/tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.  Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anion and cation transporters. No interaction is expected with emtricitabine and no significant pharmacokinetic interactions were observed when tenofovir-DF (300 mg once daily) was coadministered with entecavir (1 mg once daily). There was no change in entecavir Cmax or Cmin; however, entecavir AUC increased by 13%. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2. Emtricitabine and tenofovir are not transported by OCTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as epirubicin is glucuronidated by UGT2B7.

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

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

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

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Ergometrine is extensively metabolized, most likely by CYP3A4.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erythromycin is extensively metabolized in the liver.

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. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4.

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

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4.

Coadministration of estradiol as hormone replacement therapy has not been studied, however, coadministration of estradiol as feminising hormone therapy (FHT) has been studied in transgender women. When estradiol was administered as part of feminizing hormone therapy to 20 HIV-infected Thai transgender women receiving efavirenz and emtricitabine/tenofovir-DF, estradiol AUC, Cmax and C24 decreased by 28%, 19% and 36%, respectively, likely due to enzyme induction by efavirenz. There was no significant change in tenofovir pharmacokinetics. Coadministration of estradiol (with spironolactone) and emtricitabine/tenofovir-DF (as PrEP) to 24 transgender women had no clinically significant impact on the AUC and Cmax of estradiol. In 15 transwomen receiving emtricitabine/tenofovir-DF (200/300 mg once daily) and estradiol as a feminizing hormone, plasma tenofovir Cmax, Cmin and AUC decreased by 20%, 11% and 24% when compared to a historical control group; emtricitabine Cmax, Cmin and AUC decreased by 7%, 11% and 14%. However, intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations in PBMCs were higher than previously reported in the literature. Administration of estradiol (2 mg, with cyproterone acetate 25 mg) as feminising hormone therapy (FHT) was studied in 20 transgender women alone and with emtricitabine/tenofovir-DF. Coadministration had no significant effect on estradiol AUC (1% increase), Cmax (8% increase) or C24 (5% decrease); tenofovir AUC and C24 decreased by 13% and 17%, but Cmax increased by 10%. When tenofovir diphosphate levels (the active metabolite) were determined in rectal tissue from transgender women receiving FHT and emtricitabine/tenofovir-DF  (n=4) and post menopausal cisgender women receiving emtricitabine/tenofovir-DF (n=3),  median concentrations of tenofovir disphosphate were lower in the transgender women (53674 fmol/g, range 23240-1170302) than in the cisgender women (185158 fmol/g, range 76265-223542). The clinical relevance of this is unknown. 

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

Coadministration of emtricitabine/tenofovir-DF and ethambutol alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%). Coadministration of TB treatment containing ethambutol (with rifampicin, isoniazid and pyrazinamide) and emtricitabine/tenofovir-DF (with efavirenz) had no effect on ethambutol concentrations. Emtricitabine AUC and Cmin increased by 5% and 26% and Cmax decreased by 3%. Tenofovir AUC and Cmin increased by 13% and 9% and Cmax decreased by 2%.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Ethinylestradiol is mainly metabolized by hydroxylation and based on metabolism and clearance a clinically significant drug interaction with emtricitabine is unlikely. No clinically significant drug interactions were observed when tenofovir-DF was coadministered with a combined oral contraceptive containing ethinylestradiol/norgestimate (ethinylestradiol AUC, Cmax and Cmin decreased by 4%, 6% and 2%, respectively; norgestimate AUC and Cmax decreased by 4% and 5%). Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 1% of the oral dose is excreted as ethionamide in urine and 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 as ethosuximide is mainly oxidized by CYP3A4.

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

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway. No clinically significant drug interactions were observed when tenofovir-DF was coadministered with a COC containing ethinylestradiol/norgestimate.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoposide is partly glucuronidated by UGT1A1 and partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration with tenofovir-DF (300 mg once daily) decreased etravirine Cmax and AUC (both by 19%) and Cmin by 18%. Tenofovir Cmax and AUC both increased by 15% and Cmin increased by 19%.  No dose adjustment needed for emtricitabine/tenofovir-DF or etravirine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. There is no evidence to suggest that eucalyptus impacts UGTs or P-gp.

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Coadministration of emtricitabine and famciclovir decreased famciclovir AUC and Cmax by 9% and 7% and decreased emtricitabine AUC and Cmax by 7% and 11%. Coadministration with tenofovir-DF has not been studied but may result in increased concentrations of famciclovir and tenofovir due to competition for active tubular secretion. No a priori dosage adjustment is recommended, but renal function should be monitored. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famotidine is eliminated by renal excretion via OAT3 (65-70%) and by metabolic routes (30-35%).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is metabolised to an active metabolite, fenofibric acid: in vitro data suggest that fenofibric acid inhibits OAT3. A clinically relevant drug interaction is unlikely as emtricitabine and tenofovir are mainly excreted by different renal transporters.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally, partly by glomerular filtration and partly by active secretion via OAT1.  A clinically significant interaction is unlikely with emtricitabine. However, concentrations of flucloxacillin and tenofovir may increase due to competition for OAT1-mediated renal secretion.

Coadministration has not been studied. Fluconazole is mainly eliminated renally by glomerular filtration and is an inhibitor of CYP3A4 and P-gp. Fluconazole is unlikely to affect emtricitabine concentrations. but could potentially increase the absorption of tenofovir-DF (inhibition of P-gp), thereby increasing the systemic concentration of tenofovir. No dose adjustment is required, but monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase. A pharmacokinetic interaction is unlikely but this enzyme is also involved in the catabolic pathway of pyrimidine analogues and competition could potentially increase haematological toxicity. Monitor haematological parameters and consider dose reduction if required.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and CYP2C19.

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

Coadministration has not been studied. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. Nucleoside/nucleotide analogues such as emtricitabine and tenofovir-DF may compete for this metabolic pathway. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is predominantly metabolised via CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as the metabolism of flurazepam is most likely CYP-mediated.

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

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

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. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for an interaction is low.

Coadministration has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely as foscarnet is cleared mainly by glomerular filtration. However foscarnet is nephrotoxic and 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. Fosinopril is hydrolysed by esterases in the GI mucosa and liver.

Coadministration has not been studied. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). In vitro data indicate that furosemide is a weak inhibitor of the renal transporters OAT1/OAT3. No interaction with emtricitabine is expected and any effect on renal elimination of tenofovir is likely to be limited. No a priori dosage adjustment is recommended.

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

Coadministration has not been studied. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. A clinically significant interaction is unlikely with emtricitabine as emtricitabine is excreted by different renal transporters. However, tenofovir is primarily eliminated by the kidneys and 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 emtricitabine/tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Garlic supplements have been shown to decrease unboosted saquinavir AUC by 50% in a clinical trial likely due to induction of intestinal CYP3A4 and/or P-gp by garlic. No effect on emtricitabine is expected. Based on the drug interaction study with rifampicin (another inducer of P-gp), no significant effect is expected on tenofovir-DF.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemcitabine is metabolized in the liver by cytidine deaminase to an inactive metabolite.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gemfibrozil is metabolised mainly by UGT2B7.

Coadministration has not been studied. As gentamicin is eliminated unchanged predominantly via renal glomerular filtration, there is little potential for a pharmacokinetic interaction with emtricitabine and tenofovir due to competition for active renal transport mechanisms. However, both gentamicin and tenofovir-DF are potentially nephrotoxic and emtricitabine/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 closely monitored.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is 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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gamma-hydroxybutyrate undergoes first pass metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on absorption of tenofovir-DF is expected as gingerols are unlikely to cause clinically significant inhibition of P-gp.

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

Coadministration with emtricitabine/tenofovir-DF has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. No clinically significant interactions were observed when emtricitabine and tenofovir-DF (with efavirenz) and glecaprevir/pibrentasvir were coadministered. No dose adjustment is required.

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

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.

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. Goserelin is mainly hydrolyzed.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although grapefruit juice inhibits CYP3A4, this is not expected to alter exposure of emtricitabine or tenofovir-DF as their metabolism is not CYP-mediated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys and there is little potential for competition with emtricitabine or tenofovir for renal elimination pathways.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Halothane undergoes both oxidative and reductive metabolism by cytochromes. In vitro data have shown that oxidation occurs mainly via CYP2E1 and to a lesser extent CYP2A6 and reduction via CYP2A6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin does not undergo elimination via renal tubular secretion and 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 a clinically significant drug interaction is unlikely. When used illicitly, heroin is mainly injected or inhaled through the nose and goes directly into the bloodstream. Heroin is then rapidly deacetylated to 6-monoacetylmorhine (6-MAM) and subsequently to morphine by plasma and liver esterase, respectively. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Emtricitabine and tenofovir-DF do not affect these metabolic pathways.

Coadministration has not been studied. In vitro data indicate that extracts of hops activate PXR and induce expression of CYP3A4, CYP2B6 and MDR1 genes to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). No effect on emtricitabine is expected. Based on the drug interaction study with rifampicin (another inducer of P-gp), no significant effect is expected on tenofovir-DF.