Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of P-glycoprotein (P-gp) 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. Induction of P-gp-mediated efflux in the intestine decreases the oral bioavailability of these antiviral agents, which are substrates of the transporter. The interaction has been studied with rifampin, a potent inducer of P-gp and CYP450 isoenzymes. 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 P-gp inducers 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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.