From the Guidelines
Omeprazole should be avoided in patients taking clopidogrel due to a significant drug interaction that reduces clopidogrel's effectiveness. This interaction is attributed to omeprazole's inhibition of the CYP2C19 enzyme, which is necessary to convert clopidogrel (a prodrug) into its active form 1. The use of omeprazole with clopidogrel can increase the risk of cardiovascular events like heart attacks and strokes in patients taking clopidogrel for prevention.
Alternatives to Omeprazole
If a patient on clopidogrel requires a proton pump inhibitor for gastric protection, alternatives such as pantoprazole or dexlansoprazole are preferred as they have less impact on CYP2C19 1.
Monitoring and Considerations
The timing of administration (separating doses by 12 hours) does not reliably prevent this interaction with omeprazole because it irreversibly binds to the enzyme. For patients who absolutely require both medications, close monitoring for cardiovascular events is necessary, and healthcare providers should consider whether the benefits outweigh the risks 1. This interaction is particularly important for high-risk patients such as those with recent stent placement or acute coronary syndrome.
Evidence Summary
The evidence from various studies, including those published in Circulation and the Journal of the American College of Cardiology, suggests that while there is a pharmacodynamic interaction between omeprazole and clopidogrel, the clinical relevance of this interaction remains uncertain 1. However, given the potential risks, it is recommended to avoid the use of omeprazole in patients taking clopidogrel whenever possible.
Key Points
- Omeprazole inhibits the CYP2C19 enzyme, reducing clopidogrel's effectiveness.
- Alternatives like pantoprazole or dexlansoprazole are preferred for patients requiring a proton pump inhibitor.
- Close monitoring is necessary for patients taking both omeprazole and clopidogrel.
- The interaction is particularly important for high-risk patients, such as those with recent stent placement or acute coronary syndrome.
From the FDA Drug Label
- 6 Interaction with Clopidogrel Avoid concomitant use of omeprazole with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using omeprazole, consider alternative anti-platelet therapy [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
The interaction between clopidogrel and omeprazole is that concomitant use of these two medications should be avoided because omeprazole can impair the metabolism of clopidogrel to its active metabolite, thereby reducing the pharmacological activity of clopidogrel.
- Key points:
- Omeprazole inhibits CYP2C19 activity, which is necessary for clopidogrel activation.
- Concomitant use of clopidogrel with omeprazole reduces the effectiveness of clopidogrel.
- Alternative anti-platelet therapy should be considered when using omeprazole 2.
- Clinical decision: Avoid concomitant use of omeprazole and clopidogrel due to the potential reduction in clopidogrel's effectiveness 3.
From the Research
Interaction between Clopidogrel and Omeprazole
The interaction between clopidogrel, an antiplatelet agent, and omeprazole, a proton pump inhibitor (PPI), has been a subject of interest due to concerns that omeprazole may decrease the efficacy of clopidogrel.
- Clopidogrel is converted to its active metabolite by cytochrome P450 (CYP) enzymes, specifically CYP2C19 4.
- Omeprazole, a PPI, is also metabolized by CYP2C19, leading to the hypothesis that it may interfere with clopidogrel's action by competing for the same enzyme 4, 5.
- Some studies have suggested that concomitant use of clopidogrel and omeprazole may lead to decreased antiplatelet effects of clopidogrel, potentially increasing the risk of cardiovascular events 5, 6.
- However, other studies have found no significant interaction between clopidogrel and omeprazole in terms of cardiovascular outcomes 4, 7.
Pharmacokinetic and Pharmacodynamic Effects
- A pharmacokinetic model of the drug-drug interaction between clopidogrel and omeprazole at CYP2C19 in humans has been developed, which suggests that omeprazole can decrease the plasma levels of the active metabolite of clopidogrel, thereby reducing its antiplatelet activity 8.
- A prospective randomized crossover study found that omeprazole impairs clopidogrel-induced antiplatelet effects in the maintenance phase of treatment, regardless of the timing of their administration 6.
Clinical Implications
- The US Food and Drug Administration (FDA) recommends that concomitant use of drugs that inhibit CYP2C19, such as omeprazole, should be discouraged 4.
- However, some studies suggest that separating the administration of clopidogrel and omeprazole by 12-20 hours may minimize any potential interaction 4.
- The American Heart Association/American College of Cardiology guidelines recommend initiating a PPI, such as omeprazole, to prevent gastrointestinal bleeding in patients receiving concomitant therapy with clopidogrel and aspirin 5.