A 60-year-old man undergoes drug-eluting coronary stent placement and is started on dual antiplatelet therapy (aspirin + clopidogrel). He is also on a PPI. Which PPI interaction is most clinically significant with clopidogrel?

• A Pantoprazole raises gastric pH, reducing clopidogrel absorption by 40%
• B All PPIs equally inhibit CYP2C19 and are equally problematic with clopidogrel
• C Omeprazole significantly inhibits CYP2C19, reducing conversion of clopidogrel to its active metabolite ✓
• D PPIs compete with clopidogrel for platelet P2Y12 receptor binding

Explanation

Clopidogrel is a prodrug requiring bioactivation by CYP2C19 to its active thiol metabolite, which irreversibly alkylates the platelet P2Y12 ADP receptor. Omeprazole and esomeprazole are potent inhibitors of CYP2C19, substantially reducing clopidogrel bioactivation and the degree of platelet inhibition. Pantoprazole and rabeprazole have significantly less CYP2C19 inhibitory activity and are preferred when a PPI is necessary for gastroprotection during dual antiplatelet therapy. The FDA has issued an advisory recommending avoidance of omeprazole/esomeprazole with clopidogrel. Poor metabolizer status for CYP2C19 (pharmacogenomics) produces the same effect endogenously.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.