Drug Interactions between Eliquis and enzalutamide

GENERALLY AVOID: Coadministration with enzalutamide may decrease the plasma concentrations of apixaban. The proposed mechanism is enzalutamide-mediated induction of CYP450 3A4, the main isoenzyme responsible for the metabolism of apixaban. Enzalutamide is also considered a moderate CYP450 2C9 and 2C19 inducer in vivo; however, since metabolism of apixaban via these pathways is relatively minor, the significance remains unclear. In addition, there is conflicting evidence regarding the clinical effect of enzalutamide and its active metabolite N-desmethyl enzalutamide on the efflux transporter, P-glycoprotein (P-gp), of which apixaban is also a substrate. Both enzalutamide and N-desmethyl enzalutamide have been described in vitro as P-gp inhibitors and inducers. Although some sources propose that P-gp induction occurs in vivo, data from clinical studies evaluating transporter-mediated drug interactions of enzalutamide are not available. It is therefore difficult to predict the nature and magnitude of the effects of enzalutamide on apixaban disposition. When apixaban was coadministered with 600 mg daily of rifampin, a dual potent inducer of CYP450 3A4 and P-gp, mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 54%, respectively.

MANAGEMENT: Due to the potential for enzalutamide to alter the efficacy of apixaban, concomitant use should be avoided if possible. Otherwise, therapeutic monitoring of apixaban is advised, particularly following the initiation or discontinuation of enzalutamide.