The Effects of Lansoprazole on Clopidogrel vs. Prasugrel

the MPR take:

Clopidogrel, a P2Y12 platelet inhibitor, is metabolized to its active metabolite in part by CYP2C19. Concomitant use of certain drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. The prescribing information for clopidogrel states that the concomitant use of clopidogrel with omeprazole and esomeprazole should be avoided. Lansoprazole appears to have less of an effect, yet a new study published in the European Journal of Clinical Pharmacology states that even after doubling the clopidogrel maintenance dose (150mg), the higher platelet inhibitory effect was completely neutralized by co-administration of lansoprazole. This interaction however was not seen when lansoprazole was administered with prasugrel, also a P2Y12 platelet inhibitor. The prescribing information for prasugrel states that the drug can be administered with proton pump inhibitors, while the literature for clopidogrel says to consider using other acid-reducing agents with minimal or no CYP2C19 inhibitory effect.

Aims: The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150mg) would be less effective than switching to prasugrel 10mg maintenance dose (MD) to overcome this negative interaction.