Drug Interactions between clopidogrel and Xtandi

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 2C8 may significantly increase the plasma concentrations of enzalutamide, which is primarily metabolized by the isoenzyme. In healthy volunteers, administration of a single 160 mg oral dose of enzalutamide following multiple oral doses of the potent CYP450 2C8 inhibitor gemfibrozil resulted in a 2.2-fold increase in the composite systemic exposure (AUC) of enzalutamide plus its pharmacologically active metabolite, N-desmethyl enzalutamide, compared to administration of enzalutamide alone. There was minimal effect on the peak plasma concentration (Cmax) of enzalutamide plus N-desmethyl enzalutamide.

MANAGEMENT: The use of enzalutamide in combination with potent CYP450 2C8 inhibitors such as gemfibrozil should generally be avoided. If concomitant use is required, a reduction of the enzalutamide dosage to 80 mg once daily is recommended. Following discontinuation of the potent CYP450 2C8 inhibitor, the enzalutamide dosage should be returned to that used prior to initiation of the inhibitor.