Drug Interactions between sofosbuvir / velpatasvir / voxilaprevir and tenofovir alafenamide

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.

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.