Coadministration of omeprazole is not recommended. If it is considered medically necessary to coadminister, Epclusa should be administered with food and taken 4 hours before omeprazole 20 mg. Coadministration of omeprazole and sofosbuvir/velpatasvir (400/100 mg single dose) was studied at various doses, temporal separations and with or without food. Simultaneous administration of omeprazole (20 mg once daily) and sofosbuvir/velpatasvir to fasted subjects (n=60) decreased sofosbuvir Cmax and AUC by 34% and 29%, but increased Cmax GS-331007 by 18% and had no effect on AUC; velpatasvir Cmax and AUC decreased by 37% and 36%. When omeprazole (20 mg once daily) was administered 12 hours prior to sofosbuvir/velpatasvir in fasted subjects (n=60), sofosbuvir Cmax and AUC decreased by 45% and 44%, Cmax of GS-331007 increased by 26% but AUC decreased by 3%, and velpatasvir Cmax and AUC decreased by 57% and 55%. Coadministration of omeprazole (20 mg once daily) 2 hours prior to sofosbuvir/velpatasvir with food (n=40, compared to fasting) decreased sofosbuvir Cmax by 16% but increased AUC by 8%; Cmax and AUC of GS-331007 decreased by 6% and 1%; velpatasvir Cmax and AUC decreased by 48% and 38%. Coadministration of omeprazole (20 mg once daily) 4 hours after sofosbuvir/velpatasvir with food (n=38, compared to fasting) decreased sofosbuvir Cmax by 21% but increased AUC by 5%; Cmax and AUC of GS-331007 decreased by 9% and 1%; velpatasvir Cmax and AUC decreased by 33% and 26%. Coadministration of omeprazole (40 mg once daily) 4 hours after sofosbuvir/velpatasvir with food (n=40, compared to fasting) decreased sofosbuvir Cmax and AUC by 30% and 9%, Cmax of GS-331007 increased by 1% but AUC decreased by 1%; velpatasvir Cmax and AUC decreased by 56% and 53%.