Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of darolutamide, which is a substrate of both the isoenzyme and the efflux transporter. Reduced efficacy of darolutamide may occur. When darolutamide was coadministered with rifampin, a dual P-gp and potent CYP450 3A4 inducer, mean darolutamide peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 52% and 72%, respectively, compared to administration of darolutamide alone. The decrease in darolutamide exposure by moderate CYP450 3A4 inducers is expected to be in the range of 36% to 58% according to the prescribing information.

MANAGEMENT: Concomitant use of darolutamide with dual P-gp and potent or moderate CYP450 3A4 inducers should generally be avoided.

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.