Drug Interactions between Erleada and Plavix

GENERALLY AVOID: Coadministration with potent inducers of CYP450 2C19 may enhance the metabolic activation of clopidogrel, resulting in increased platelet inhibition and possibly bleeding risk. Clopidogrel is a prodrug that is converted to its active metabolite (AM) primarily by CYP450 2C19, with contributions from several other CYP450 isoenzymes including CYP450 3A, 2B6, and 1A2. When clopidogrel (600 mg loading dose followed by 75 mg once daily for 7 days) was coadministered with the potent CYP450 2C19 and 3A4 inducer rifampin (300 mg twice daily for 14 days) in twelve healthy volunteers, mean clopidogrel AM peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 3.8-fold. Mean inhibition of platelet aggregation at 4 hours post loading dose was 34% higher in the presence of rifampin compared to clopidogrel administered alone. When clopidogrel (75 mg once daily for 6 days) was coadministered with rifampin (300 mg twice daily for 10 days) in another study of ten healthy volunteers, platelet aggregation was 33% as compared to 56% following clopidogrel alone for 6 days and 94% at baseline.

MANAGEMENT: Concomitant use of clopidogrel with potent CYP450 2C19 inducers should be avoided when possible. If coadministration is required, patients should be monitored closely for signs of bleeding.