Drug Interaction Report

ADJUST DOSE: Coadministration with darolutamide may significantly increase the plasma concentrations of rosuvastatin. The proposed mechanism is darolutamide inhibition of intestinal and hepatobiliary efflux of rosuvastatin via breast cancer resistance protein (BCRP). When rosuvastatin, a known BCRP substrate, was administered concomitantly with darolutamide, mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 5-fold. High levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: The daily dosage of rosuvastatin should not exceed 5 mg when used in combination with darolutamide. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Alternatively, a different HMG-CoA reductase inhibitor that is not a substrate for BCRP may be considered. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

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.