No drug interaction trials have been conducted using TRUVADA tablets. Drug interaction trials have been conducted with emtricitabine and tenofovir DF, the components of TRUVADA. This section describes clinically relevant drug interactions observed with emtricitabine and tenofovir DF [see CLINICAL PHARMACOLOGY (12.3)].

7.1 Didanosine

Coadministration of TRUVADA and didanosine should be undertaken with caution, and patients receiving this combination should be monitored closely for didanosine-associated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions.

When tenofovir DF was administered with didanosine the Cmax and AUC of didanosine increased significantly [see CLINICAL PHARMACOLOGY (12.3)]. The mechanism of this interaction is unknown. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis, and neuropathy. Suppression of CD4+ cell counts has been observed in patients receiving tenofovir DF with didanosine 400 mg daily.

In patients weighing greater than 60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with TRUVADA. Data are not available to recommend a dose adjustment of didanosine for adult or pediatric patients weighing less than 60 kg. When coadministered, TRUVADA and Videx EC may be taken under fasted conditions or with a light meal (less than 400 kcal, 20% fat).

7.2 HIV-1 Protease Inhibitors

Tenofovir decreases the AUC and Cmin of atazanavir [see CLINICAL PHARMACOLOGY (12.3)]. When coadministered with TRUVADA, it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. TRUVADA should not be coadministered with atazanavir without ritonavir.

Lopinavir/ritonavir, atazanavir coadministered with ritonavir, and darunavir coadministered with ritonavir have been shown to increase tenofovir concentrations [See CLINICAL PHARMACOLOGY (12.3)]. Tenofovir DF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. When tenofovir DF is coadministered with an inhibitor of these transporters, an increase in absorption may be observed. Patients receiving TRUVADA concomitantly with lopinavir/ritonavir, ritonavir-boosted atazanavir, or ritonavir-boosted darunavir should be monitored for tenofovir DF-associated adverse reactions. TRUVADA should be discontinued in patients who develop tenofovir DF-associated adverse reactions.

7.3 Hepatitis C Antiviral Agents

Coadministration of TRUVADA and EPCLUSA® (sofosbuvir/velpatasvir) or HARVONI®(ledipasvir/sofosbuvir has been shown to increase tenofovir exposure [see CLINICAL PHARMACOLOGY (12.3)].

In patients receiving TRUVADA concomitantly with EPCLUSA, monitor for adverse reactions associated with tenofovir DF.

In patients receiving TRUVADA concomitantly with HARVONI without an HIV-1 protease inhibitor/ritonavir or an HIV-1 protease inhibitor/cobicistat combination, monitor for adverse reactions associated with tenofovir DF.

In patients receiving TRUVADA concomitantly with HARVONI and an HIV-1 protease inhibitor/ritonavir or an HIV-1 protease inhibitor/cobicistat combination, consider an alternative HCV or antiretroviral therapy, as the safety of increased tenofovir concentrations in this setting has not been established. If coadministration is necessary, monitor for adverse reactions associated with tenofovir DF.

7.4 Drugs Affecting Renal Function

Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion [see CLINICAL PHARMACOLOGY (12.3)]. No drug-drug interactions due to competition for renal excretion have been observed; however, coadministration of TRUVADA with drugs that are eliminated by active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see WARNINGS AND PRECAUTIONS (5.2)]. Drugs that decrease renal function may increase concentrations of emtricitabine and/or tenofovir.