Clopidogrel & PPIs

Q: Which of the following Proton Pump Inhibitors (PPIs) is most likely to decrease the effect of clopidogrel? - select one

A) Lansoprazole

B) Omeprazole

C) Pantoprazole

D) Rabeprazole 

Answer: B

The interaction between clopidogrel and PPIs is overrated. Two ways to minimize this interaction are:

1. Avoid omeprazole, as clopidogrel and omeprazole share hepatic CYP2C19 metabolism. Other PPIs like pantoprazole, lansoprazole, and rabeprazole are less likely to interact. 

2. Taking clopidogrel and PPIs four or more hours apart.

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References:

1. Axelsson MAB, Parodi López N, Wikström Jonsson E, Wallerstedt SM. Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis. Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70087. doi: 10.1111/bcpt.70087. PMID: 40685887; PMCID: PMC12277936.

2. Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation 2009; 120:2310.