Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of darolutamide, which is a substrate of both the isoenzyme and the efflux transporter. When darolutamide was coadministered with itraconazole, a dual P-gp and potent CYP450 3A4 inhibitor, mean darolutamide peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 40% and 70%, respectively, compared to administration of darolutamide alone. The interaction has not been studied with less potent inhibitors or lone inhibitors of CYP450 3A4 or P-gp. Caution is advised when darolutamide is used with CYP450 3A4 or P-gp inhibitors. Patients should be monitored more frequently for adverse effects such as fatigue, hypertension, neutropenia and abnormal liver function tests, and the darolutamide dosage adjusted as necessary in accordance with the product labeling.

ADJUST DOSING INTERVAL: Food enhances the oral absorption of darolutamide. According to the prescribing information, bioavailability of darolutamide increased by 2.0 to 2.5-fold when administered with food. A similar increase in exposure was observed for the active metabolite keto-darolutamide.

MANAGEMENT: Darolutamide should be administered with food.