Drug Interaction Report

MONITOR: Coadministration with omeprazole may decrease the plasma concentrations of glecaprevir. The mechanism of interaction has not been established. When a single 300 mg-120 mg dose of glecaprevir-pibrentasvir was administered with omeprazole 20 mg once daily to 9 study subjects, glecaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 22% and 29%, respectively. When the dose of glecaprevir-pibrentasvir was administered with omeprazole 40 mg once daily (one hour before glecaprevir-pibrentasvir) to 12 study subjects, glecaprevir Cmax decreased by 64% and AUC decreased by 51%. The pharmacokinetics of pibrentasvir were not affected.

MANAGEMENT: According to the manufacturer, no dosage adjustment is necessary for glecaprevir-pibrentasvir during coadministration with omeprazole. However, the potential for diminished pharmacologic effects of glecaprevir-pibrentasvir should be considered during coadministration with higher dosages of omeprazole. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.