Drug Interactions between darolutamide and Vyxeos

MONITOR: The concomitant or sequential administration of multiple antineoplastic agents may result in additive toxicities, particularly in the bone marrow, gastrointestinal tract and heart.

MANAGEMENT: Close clinical and laboratory monitoring for hematologic and nonhematologic toxicities are recommended when antineoplastic agents are administered concurrently or during close intervals. Dosing adjustments may be necessary. The manufacturers' recommendations and institutional protocols for dosage, treatment regimens, monitoring, and management of toxicities should be consulted.

GENERALLY AVOID: Coadministration with darolutamide may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is decreased clearance due to inhibition of BCRP-mediated intestinal and hepatobiliary efflux by darolutamide. 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.

MANAGEMENT: Concomitant use of darolutamide with drugs that are BCRP substrates should be avoided when possible. If coadministration is required, patients should be monitored carefully for increased adverse reactions of these drugs and dosing adjusted as necessary.