Drug Interaction Report

MONITOR: Based on in vitro data, coadministration with enasidenib may increase the plasma concentrations of drugs that are substrates of the transporters, organic anion transporting polypeptides (OATP) 1B1/1B3 and breast cancer resistance protein (BCRP). The proposed mechanism is decreased clearance due to enasidenib -mediated inhibition of OATP1B1/1B3 and BCRP transporters. There are no clinical data regarding the use of enasidenib with these substrates.

MANAGEMENT: Caution is advised when enasidenib is used concurrently with medications that are substrates of OATP 1B1/1B3 and/or BCRP, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever enasidenib is added to or withdrawn from therapy.

Food does not appear to have clinically significant effects on the pharmacokinetics of elbasvir and grazoprevir. When a single 50 mg-100 mg dose of elbasvir-grazoprevir was administered to healthy study subjects with a high-fat meal (900 kcal; 500 kcal from fat), elbasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 15% and 11%, respectively, while grazoprevir Cmax and AUC increased by 2.8- and 1.5-fold, respectively, compared to administration under fasting conditions. According to the product labeling, elbasvir-grazoprevir may be administered with or without food.