Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on tenofovir AUC or Cmax, and abacavir AUC; abacavir Cmax increased by 12%. A high rate of virological failure and emergence of resistance have been reported when lamivudine was combined with tenofovir-DF and abacavir as a once-daily regimen. However, this is not relevant when tenofovir-DF is prescribed for HBV.

Coadministration has not been studied but could potentially result in an increased risk of nephrotoxicity. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has low body weight, or receives other drugs that may increase tenofovir exposure. 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. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied but may increase concentrations of both drugs due to reduced renal function or competition for active tubular secretion as aciclovir is also excreted via OAT1/3.

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

Adefovir should not be coadministered with tenofovir-DF. However, no pharmacokinetic effect was observed when adefovir and tenofovir-DF were administered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is hepatically metabolised therefore the potential for interactions via this pathway is low. [Note, the European SmPC and US Prescribing Information for allopurinol recommend reduced dose in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amikacin is eliminated renally by glomerular filtration and tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4 therefore the potential for interactions via this pathway is low. However, 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. 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 tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. Amphotericin B is eliminated unchanged via urinary and biliary excretion (biliary excretion is lower with lipid formulated amphotericin).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir-DF is cleared renally by OAT1/3. Anakinra does not interact with this pathway. Anakinra is an IL-1 receptor antagonist and is eliminated by glomerular filtration and subsequent tubular metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apalutamide is metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Tenofovir-DF is cleared renally by OAT1/3.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). However, coadministration could potentially result in an increased risk of nephrotoxicity. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has low body weight, or receives other drugs that may increase tenofovir exposure. 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. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

In a combined analysis of several clinical studies with tenofovir-DF (300 mg) and atazanavir/ritonavir (300/100 mg), atazanavir AUC, Cmax and Cmin decreased by 22%, 16% and 23%, respectively, and tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. Patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. A dose increase to atazanavir/ritonavir 400/100 mg with TDM may be considered during the second and third trimesters of pregnancy. If atazanavir/ritonavir with tenofovir-DF OR an H2-receptor antagonist are coadministered during the second and third trimesters of pregnancy, a dose increase to atazanavir/ritonavir 400/100 mg is recommended. It is not recommended to use atazanavir with ritonavir for pregnant patients who are receiving both tenofovir-DF AND an H2-receptor antagonist.

Coadministration with atazanavir alone is not recommended. Coadministration of tenofovir-DF (300 mg) and atazanavir (400 mg) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively, but increased tenofovir AUC, Cmax and Cmin by 24%, 14% and 22%, respectively. If coadministration is necessary, patients should be closely monitored for tenofovir-associated adverse events, including renal disorders

Coadministration has not been studied. The combination of tenofovir-DF (300 mg) and atazanavir (400 mg) reduced atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively, but increased tenofovir AUC, Cmax and Cmin by 24%, 14% and 22%, respectively. Atazanavir/cobicistat is also expected to increase tenofovir plasma concentrations. Patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. The European SmPC recommends that atazanavir/cobicistat and tenofovir be given together with food. 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 in patients with creatinine clearance less than 70 ml/min.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Tenofovir is eliminated renally. Bamlanivimab and etesevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Tenofovir is eliminated renally. Baricitinib does not inhibit renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Bendroflumethiazide is eliminated by hepatic metabolism (70%) 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.

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

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. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Tenofovir disoproxil nor tenofovir are not hepatically metabolised therefore the potential for interactions via this pathway is low. There is no evidence that bisoprolol and tenofovir are eliminated by the same renal transporters. [Note, the European SmPC for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment whereas the US Prescribing Information recommends an initial 2.5 mg in hepatic impairment with caution in further dose titration.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction Is unlikely. Black cohosh does not appear to be a potent modulator of human drug metabolism. Standardized black cohosh supplements, when taken at recommended doses, pose little risk for herb-drug interactions. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes, therefore, the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin releases the active species MMAE within the tumour cell; MMAE is a substrate of CYP3A4, P-gp, and possibly CYP2D6. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brexpiprazole is predominantly metabolized by CYP3A4 and CYP2D6. Neither tenofovir disoproxil nor tenofovir is metabolized by the CYP450 enzymes therefore the potential for interactions via this pathway is low. Tenofovir-DF is cleared renally by OAT1/3. Brexpiprazole does not interact with these pathways.

Coadministration has not been studied. Brincidofovir is a prodrug converted to cidofovir, which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Unlike cidofovir, brincidofovir is not a substrate of OATs and therefore is less likely to accumulate in the kidney thereby reducing the potential for nephrotoxicity. Furthermore, the administration of oral brincidofovir leads to cidofovir plasma concentrations <1% of those observed after IV cidofovir. Tenofovir is primarily eliminated by the kidneys notably via OAT1, however, given that brincidofovir is not a substrate of this transporter no pharmacokinetic interaction is expected. Brincidofovir inhibits BCRP but not P-gp and therefore could increase tenofovir-DF exposure although to a limited extent.

The interaction between buprenorphine and didanosine, lamivudine, and tenofovir-DF was investigated in 27 HIV-negative, buprenorphine/naloxone-maintained subjects. When compared to values obtained from 20 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 formally studied but based on current knowledge of the effect of vaccines on drug disposition a clinically significant interaction is considered unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4 therefore the potential for interactions via this pathway is low.

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. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleotide analogues such as tenofovir-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 tenofovir for renal elimination transport mechanisms resulting in increased concentrations of either drug. Renal toxicity has been reported during capreomycin treatment. 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 pharmacokinetic interaction is unlikely. Carfentanil is expected to be metabolized by CYP3A4/5. Tenofovir-DF does not interact with this pathway. However, carfentanil is an extremely strong opiate, reported to be up to 10,000 times more potent than morphine, and multiple deaths have resulted from its use. Advise patients to avoid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Neither tenofovir disoproxil nor tenofovir is metabolized by the CYP450 enzymes therefore the potential for interactions via this pathway is low. Tenofovir-DF is cleared renally by OAT1/3. Cariprazine does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Tenofovir is eliminated renally. Casirivimab and imdevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Casirivimab and imdevimab are not renally excreted. Interactions with concomitant medications that are renally excreted are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non-CYP-mediated pathway. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4 therefore the potential for interactions via this pathway is low. [Note, no dose adjustment is required in patients with normal hepatic function but a dose reduction of caspofungin daily dose to 35 mg is recommended for adults with moderate hepatic impairment. There is no clinical experience in adults with severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw is a CYP3A4 inhibitor. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes, therefore, the potential for interactions via this pathway is low.

Coadministration has not been studied but could potentially result in an increased risk of nephrotoxicity. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has low body weight, or receives other drugs that may increase tenofovir exposure. 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. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately. [Note, use in patients with severe liver impairment is contraindicated in the European SmPC and not recommended in the US Prescribing Information. In patients with moderate liver impairment (serum albumin 25-35 g/L, Child-Pugh Class B), celecoxib treatment should be started at half the recommended dose.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is a substrate of CYPs 2D6 (major), 1A2, and 3A4 in vitro. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorprothixene is metabolised by CYP2D6. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied. Since tenofovir-DF 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. Cilazapril is mainly eliminated unchanged by the kidneys. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4 therefore the potential for interactions via this pathway is low. [Note, in patients with cirrhosis, a maximum dose of 0.5 mg/day is recommended as significant hypotension may occur.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 at concentrations much higher than the observed clinical concentrations. No interaction is expected with tenofovir. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4 therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. As renal excretion has a minor role in clofazimine elimination, an interaction with tenofovir-DF via competition for renal elimination pathways is unlikely.

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. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4. Neither tenofovir disoproxil nor tenofovir is metabolized by the CYP450 enzymes therefore the potential for interactions via this pathway is low. Tenofovir-DF is cleared renally by OAT1/3.

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 tenofovir-DF is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Danaparoid is renally excreted by unknown mechanisms. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4, therefore the potential for interactions via this pathway is low.

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 tenofovir-DF. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4, therefore the potential for interactions via this pathway is low.

Note: this interaction was studied using a darunavir/ritonavir dose lower than that licensed. Coadministration of tenofovir-DF (300 mg once daily) and darunavir/ritonavir (300/100 mg twice daily) increased darunavir Cmax (16%), AUC (21%) and Cmin (24%). Tenofovir Cmax, AUC and Cmin increased by 24%, 22% and 37%, respectively. No adjustments to the licensed doses are required. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir or cobicistat boosted protease inhibitor. Close monitoring of renal function and for tenofovir-associated adverse reactions is required in these patients.

Symtuza (darunavir, cobicistat, emtricatabine, tenofovir alafenamide) contains tenofovir alafenamide and must not be administered with tenofovir-DF.

Coadministration has not been studied but 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. However, 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.

No clinically significant interaction was observed when delamanid and tenofovir-DF were coadministered. Coadministration of delamanid (100 mg twice daily) and tenofovir-DF (300 mg once daily) did not affect delamanid Cmax (16% decrease) or AUC (4% decrease). Tenofovir exposure was unchanged (11% decrease in Cmax, 9% decrease in AUC; n=13).

Coadministration 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. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is a substrate of CYP3A4. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but could potentially result in an increased risk of nephrotoxicity. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has low body weight, or receives other drugs that may increase tenofovir exposure. 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. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately. [Note, use in patients with severe hepatic impairment (Child-Pugh class C) is contraindicated in the European product label for dexketoprofen.]

Coadministration has not been studied but could potentially decrease renal elimination of tenofovir-DF (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 and close monitoring of renal function.

Coadministration is not recommended due to increased didanosine concentrations and toxicity. If this combination is judged strictly necessary, patients should be carefully monitored for efficacy and didanosine related adverse events. The US Prescribing Information for didanosine and tenofovir-DF recommend a reduced dose of didanosine (250 mg once daily for adults weighing 60 kg or greater with creatinine clearance 60 mL/min or greater; 200 mg once daily for adults weighing less than 60 kg with creatinine clearance 60 mL/min or greater). A decreased dosage of 250 mg didanosine with tenofovir-DF has been associated with reports of high rates of virological failure within several tested combinations for the treatment of HIV-1 infection.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dienogest is a substrate of CYP3A4. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low. [Note, diphenhydramine should be used with caution in patients with moderate to severe hepatic impairment.]

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

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. No dosage adjustment is necessary.

Coadministration with dolutegravir/rilpivirine has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. 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 of rilpivirine (150 mg once daily) and tenofovir-DF (300 mg once daily) decreased rilpivirine Cmax and Cmin by 4% and 1% and increased AUC by 1%. Tenofovir Cmax, AUC and Cmin increased by 19%, 23% and 24%. Note, Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with products also for the treatment of HIV.

Coadministration has no significant effect on the pharmacokinetics of doravirine or tenofovir. Coadministration of doravirine (100 mg single dose) and tenofovir-DF (300 mg once daily) decreased doravirine AUC, Cmax and C24 by 3%, 18% and 5%, respectively (n=8).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dosulepin is extensively metabolised in the liver, likely by CYP2D6 (major) and CYP3A4. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low. [Note: Dosulepin should be used with caution in mild to moderate hepatic impairment and avoided in severe hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low. [Note, the European SmPC does not recommend doxazosin in severe hepatic impairment; the US Prescribing Information has a caution for use in hepatic impairment.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized mainly by CYP2C19 to nordoxepin, an active metabolite. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low. [Note, the European and US product labels for doxepin advise caution and monitoring in patients with hepatic impairment as a dosage reduction may be required.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolized primarily by CYP2D6, CYP1A2, and CYP2C9. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration 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. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Drospirenone is metabolised in part by CYP3A4. These pathways are not affected by tenofovir-DF.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. [Note, duloxetine is contraindicated in patients with hepatic impairment as concentrations may increase due to decreased clearance of duloxetine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Tenofovir is eliminated renally via the proximal tubule mainly by OAT1, with some contribution from OAT3, and into urine by MPR4. Neither tenofovir disoproxil nor tenofovir is metabolised by the CYP450 enzymes therefore the potential for interactions via this pathway is low. [Note, the European SmPC (but not the US Prescribing Information) cautions against dutasteride use in mild to moderate hepatic impairment and contraindicates it in severe hepatic impairment.]

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

Coadministration of tenofovir-DF (300 mg once daily) and efavirenz (600 mg once daily) had no effect on the Cmax, AUC or Cmin of either tenofovir or efavirenz.

The interaction between elbasvir/grazoprevir and tenofovir-DF was evaluated in clinical studies, and no dose adjustments are required. There was no clinically significant effect on tenofovir pharmacokinetics when administered with elbasvir (tenofovir AUC, Cmax, Ctrough increased by 34%, 47%, 29%) or grazoprevir (tenofovir AUC, Cmax, Ctrough increased by 18%, 14% and 24%). Tenofovir-DF had no clinically significant effect on elbasvir (AUC, Cmax, C24 decreased by 7%, 12% and 8%) or grazoprevir (AUC, Cmax, C24 decreased by 14%, 22% and 11%).

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 tenofovir-DF used for the treatment of HIV or hepatitis B virus infection.

Stribild contains tenofovir-DF and should not be coadministered with other products containing tenofovir-DF used for the treatment of HIV or hepatitis B virus infection.

No significant interactions were observed between emtricitabine and tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily) and emtricitabine (200 mg once daily for 7 days) had no effect on tenofovir AUC, Cmax or Cmin. Emtricitabine AUC and Cmax were unaltered and there was a 20% increase in Cmin.

Descovy contains tenofovir alafenamide and therefore should not be administered with additional tenofovir-DF.