Concomitant administration of sofosbuvir/velpatasvir with efavirenz resulted in a reduction (approximately 50%) in the systemic exposure of velpatasvir. The mechanism of the effect on velpatasvir is induction of CYP3A and CYP2B6 by efavirenz. Coadministration of sofosbuvir/velpatasvir with efavirenz is not recommended. Refer to the prescribing information for sofosbuvir/velpatasvir for more information. Sofosbuvir and efavirenz concentrations were unchanged.

Coadministration wasn’t studied but is expected to decrease velpatasvir concentrations. Coadministration of efavirenz and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir.

Coadministration of sofosbuvir/velpatasvir (400/100 mg, once daily) and efavirenz (600 mg once daily, with emtricitabine and tenofovir-DF) was studied in 15 healthy volunteers in a cross-over study. Sofosbuvir AUC decreased by 3% and Cmax increased by 38%; AUC and Cmax of GS-331007 decreased by 10% and 14%, but Cmin increased by 1%. Velpatasvir AUC, Cmax and Cmin decreased by 53%, 47% and 57%, respectively. Efavirenz AUC, Cmax and Cmin decreased by 15%, 19% and 10%, respectively. Use of sofosbuvir/velpatasvir with efavirenz-containing regimens is not recommended due the ~50% reduction in velpatasvir exposure.