Drug Interaction Report

ADJUST DOSE: Coadministration of ledipasvir with proton pump inhibitors may reduce its gastrointestinal absorption. Ledipasvir exhibits pH-dependent solubility, with increased solubility at lower pH. In 17 healthy volunteers, mean ledipasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 42%, respectively, when a single 30 mg dose of ledipasvir was administered 2 hours after omeprazole given at a dosage of 20 mg once daily. When a single 90 mg-400 mg dose of ledipasvir-sofosbuvir was administered simultaneously with omeprazole 20 mg once daily, mean ledipasvir Cmax decreased by 11% and AUC decreased by just 4%.

MANAGEMENT: Proton-pump inhibitors at doses comparable to omeprazole 20 mg or lower should only be administered either simultaneously with or up to 2 hours after ledipasvir-sofosbuvir under fasted conditions. Some authorities advise against administering proton pump inhibitors before ledipasvir-containing products; however, a timeframe of dosage separation has not been specified.

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.