Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 isoenzymes may decrease the plasma concentrations of velpatasvir, which has been shown in vitro to be metabolized by CYP450 2B6, 2C8, and 3A4. The interaction has been studied with efavirenz, a moderate CYP450 2B6 and 3A4 inducer. In 14 healthy volunteers, administration of sofosbuvir-velpatasvir 400 mg -100 mg once daily with efavirenz/emtricitabine/tenofovir disoproxil fumarate 600 mg/200 mg/300 mg once daily decreased mean velpatasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 47%, 53% and 57%, respectively, compared to administration of sofosbuvir-velpatasvir alone. No clinically relevant pharmacokinetic changes were observed for sofosbuvir or its predominant circulating metabolite, GS-331007.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of sofosbuvir-velpatasvir with potent or moderate CYP450 inducers is not recommended.

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.