Drug Interaction Report

MONITOR: Coadministration of tenofovir disoproxil fumarate with velpatasvir may increase the plasma concentrations of tenofovir. The proposed mechanism is inhibition of the P-glycoprotein (P-gp) transporter-mediated efflux of tenofovir DF by velpatasvir. In pharmacokinetic studies, administration of various tenofovir DF-containing products or antiretroviral regimens in combination with sofosbuvir-velpatasvir 400 mg-100 mg once daily to healthy volunteers resulted in approximately 1.3- to 1.8-fold increases in tenofovir systemic exposure (AUC). In contrast, no significant interaction was observed with tenofovir alafenamide.

MANAGEMENT: Caution is advised when tenofovir disoproxil fumarate is prescribed with sofosbuvir-velpatasvir. Renal function should be closely monitored.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.