Drug interaction between clopidogrel and proton pump inhibitors

Dual antiplatelet therapy with aspirin and clopidogrel is essential after percutaneous coronary intervention. Clopidogrel is a prodrug and requires metabolism by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are metabolized by CYP2C19. Concomitant use of PPI in dual antiplatelet therapy diminishes the antiplatelet effect of clopidogrel, although it is controversial whether its clinical efficacy is reduced. The US FDA and European Medicines Agency recommend that PPIs and clopidogrel should not be coadministered routinely, and the 2010 expert consensus of ACCF/AGC/AHA supports this recommendation. On the other hand, histamine receptor type 2 (H2) blockers also reduce gastric acid secretion and are used for the treatment of gastroduodenal ulcers. Famotidine, an H2 blocker, has been shown recently to reduce gastric mucosal injury caused by aspirin therapy, although the protective effects of H2 blockers are weaker than that of PPI. Therefore, H2 blockers except cimetidine, which is inactivated by CYP2C19, could be an alternative for PPI in patients treated with clopidogrel, who are at risk of low gastrointestinal tract bleeding.