Drug Interactions between darolutamide and Rezulin

MONITOR: Coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of darolutamide, which is a substrate of both the isoenzyme and the efflux transporter. 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 dual P-gp and moderate CYP450 3A4 inducers is expected to be in the range of 36% to 58% according to the prescribing information. The interaction has not been studied with lone inducers of CYP450 3A4 or P-gp. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: The potential for diminished pharmacologic effects of darolutamide should be considered during coadministration with CYP450 3A4 and/or P-gp inducers. Alternative treatments may be required if an interaction is suspected. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath. The prescribing information for the concomitant CYP450 3A4 inducers should be consulted for specific recommendations.

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