Omeprazole (20 mg once daily) was studied with Vosevi (400/100/100 mg single dose). When dosed 2 hours prior to Vosevi, sofosbuvir Cmax and AUC decreased by 23% and 27%, velpatasvir Cmax and AUC decreased by 57% and 54%, and voxilaprevir Cmax decreased 24% with no change in AUC (increase in gastric pH decreases velpatasvir solubility). When omeprazole was dosed 4 hours after Vosevi, there was no change in the Cmax or AUC of sofosbuvir or voxilaprevir, but velpatasvir Cmax and AUC both decreased by 51%. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Velpatasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of velpatasvir. Omeprazole 20 mg can be administered with Vosevir. Use with other proton pump-inhibitors has not been studied. Coadministration of omeprazole (20 mg once daily, 2 hours prior to Vosevi) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose) was studied in 34 subjects. Sofosbuvir Cmax and AUC decreased by 23% and 27%; GS-331007 Cmax increased by 27% and AUC decreased by 3%; velpatasvir Cmax and AUC decreased by 57% and 54%; voxilaprevir Cmax and AUC decreased by 24% and 20%. Coadministration of omeprazole (20 mg once daily, 4 hours after Vosevi) and sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg single dose) was studied in 34 subjects. Sofosbuvir Cmax and AUC decreased by 6% and 18%; GS-331007 Cmax increased by 19% and AUC decreased by 1%; velpatasvir Cmax and AUC decreased by 51% and 51%; voxilaprevir Cmax increased by 8% and AUC decreased by 5%.