Drug Interactions between Plavix and ticlopidine

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 2C19 may reduce the efficacy of clopidogrel, whose antiplatelet effect is dependent in part on bioactivation by the isoenzyme to a pharmacologically active metabolite. This is consistent with studies that reported decreased effectiveness of clopidogrel and poorer clinical outcome in patients who have common genetic polymorphisms of CYP450 2C19 resulting in reduced or absent enzyme activity. The interaction has been studied with omeprazole, a potent CYP450 2C19 inhibitor. In 72 healthy subjects administered clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg) simultaneously for 5 days, systemic exposure to the active metabolite of clopidogrel decreased by 46% (Day 1) and 42% (Day 5) during coadministration with omeprazole, while mean inhibition of platelet aggregation (IPA) diminished by 47% (24 hours) and 30% (Day 5). Similar results were reported when the same doses of clopidogrel and omeprazole were administered 12 hours apart in another study.

MANAGEMENT: Based on existing data, patients treated with clopidogrel should preferably avoid the concomitant use of potent CYP450 2C19 inhibitors such as fluconazole, fluoxetine, fluvoxamine, and ticlopidine. Concomitant use of selective serotonin reuptake inhibitors or ticlopidine with clopidogrel may also potentiate the risk of bleeding complications due to additive or synergistic effects on the clotting cascade.