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PPI–Clopidogrel Interaction — PSA MCQ

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ModerateCardiologyPPI–Clopidogrel InteractionPSAMRCGP AKTUKMLA

A 65-year-old man is discharged after an NSTEMI on aspirin and clopidogrel. Because of previous peptic ulcer bleeding, proton-pump inhibitor gastroprotection is indicated. According to UK medicines advice, which pair of PPIs has the lowest probability of a clinically significant interaction with clopidogrel?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: D — Pantoprazole and rabeprazole

D is correct. Clopidogrel is a prodrug activated partly through CYP2C19. Omeprazole and esomeprazole inhibit this enzyme and have the highest probability of reducing exposure to active clopidogrel, so their concurrent use is discouraged. Lansoprazole has an intermediate interaction probability. Pantoprazole and rabeprazole have the lowest probability of a clinically significant interaction and are suitable alternatives when PPI gastroprotection is required. Options A–C each include omeprazole or esomeprazole, while option E includes lansoprazole and therefore does not identify the two lowest-interaction PPIs. The effect of these pharmacokinetic differences on cardiovascular outcomes remains uncertain, but UK prescribing recommendations use them to guide PPI selection.

Reference: NHS Specialist Pharmacy Service. Using clopidogrel with proton pump inhibitors (PPIs), updated 14 September 2023. https://www.sps.nhs.uk/articles/using-clopidogrel-with-proton-pump-inhibitors-ppis/