Clopidogrel and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Clopidogrel
Ketoconazole
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduction in clinical efficacy of clopidogrel
Interaction Deep Dive
Clopidogrel is metabolized to its active metabolite by CYP2C19. Although the interaction between clopidogrel and ketoconazole has not been studied, coadministration of omeprazole, a CYP2C19 inhibitor like ketoconazole, with clopidogrel resulted in reduced clopidogrel active metabolite concentrations and reduced platelet inhibition. A similar interaction would be expected between clopidogrel and other CYP2C19 inhibitors. Because of the potential for reduced clopidogrel efficacy, concomitant use of CYP2C19 inhibitors including ketoconazole, with clopidogrel should be avoided1.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated clopidogrel metabolism to active metabolite by ketoconazole
Literature reports
1 report — tap to read
a) Exposure to the active metabolite of clopidogrel was decreased by 46% on day 1 and 42% on day 5 when healthy subjects were coadministered clopidogrel at a 300-mg loading dose followed by 75 mg/day and omeprazole 80 mg (another CYP2C19 inhibitor like ketoconazole) compared with the same dose of clopidogrel given alone for 5 days in a crossover clinical study (n=72). Mean inhibition of platelet aggregation also decreased by 47% at 24 hours and 30% on day 5 when clopidogrel and omeprazole were given concomitantly. Results were similar when clopidogrel and omeprazole were given at the same doses, but administered 12 hours apart in another study of healthy subjects (n=72). This indicates that an interaction between clopidogrel and omeprazole is not prevented even when administering the drugs at different times 1.
Common questions
Can I take Clopidogrel and Ketoconazole together?
Reduction in clinical efficacy of clopidogrel Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clopidogrel and Ketoconazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Clopidogrel or Ketoconazole need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: PLAVIX(R) oral tablets, clopidogrel bisulfate oral tablets. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Bridgewater, NJ, 2009. DailyMed
Keep reading about Clopidogrel
Keep reading about Ketoconazole
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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