Drug Interactions between rifampin and sofosbuvir / velpatasvir

GENERALLY AVOID: Coadministration with rifampin may significantly decrease the plasma concentrations of sofosbuvir and other direct-acting antiviral agents that may be given with sofosbuvir in fixed-dose combination products such as ledipasvir and velpatasvir. The proposed mechanism is induction of intestinal P-glycoprotein (P-gp)-mediated efflux by rifampin, which results in decreased oral bioavailability of the antiviral agents. Induction of CYP450 2B6, 2C8, and 3A4 may also contribute in the case of velpatasvir. In 17 healthy volunteers, administration of a single 400 mg dose of sofosbuvir during multiple dosing of rifampin 600 mg once daily reduced mean sofosbuvir peak plasma concentration (Cmax) and systemic exposure (AUC) by 77% and 72%, respectively. Likewise, administration of a single 90 mg dose of ledipasvir to 31 healthy volunteers during multiple dosing of rifampin 600 mg once daily decreased mean ledipasvir Cmax and AUC by 35% and 59%, respectively. When a single 100 mg dose of velpatasvir was given with rifampin 600 mg once daily to 12 healthy volunteers, velpatasvir Cmax decreased by 71% and AUC decreased by 82%.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of rifampin should generally be avoided during treatment with sofosbuvir, given either as a single-ingredient product or as a fixed-dose combination product with ledipasvir or velpatasvir.