Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 that can also inhibit P-glycoprotein (P-gp) may significantly 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.

MANAGEMENT: Caution is advised when darolutamide is used with dual P-gp and potent CYP450 3A4 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.

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 absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

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.