Clopidogrel and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Clopidogrel
Simvastatin
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
Decreased formation of clopidogrel active metabolite resulting in high on-treatment platelet reactivity
Interaction Deep Dive
Patients treated with clopidogrel, which is partially metabolized to its active metabolite by CYP3A4 and P-glycoprotein efflux transport, may develop high on-treatment platelet reactivity with concomitant use of a CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin). In a clinical study, patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity during concurrent use of clopidogrel and atorvastatin demonstrated a significant reduction in platelet reactivity and enhanced clinical response to clopidogrel after switching to pravastatin or rosuvastatin (both non-CYP3A4-metabolized statins). If a patient develops high on-treatment platelet reactivity during concomitant treatment with clopidogrel and a CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin), consider discontinuation of that statin, and substitution with a statin that is not metabolized by CYP3A4 (ie, pravastatin or rosuvastatin)1.
Why it happens (mechanism)
Competition with CYP3A4-mediated metabolism and inhibition of P-glycoprotein efflux transport of clopidogrel by CYP3A4-metabolized statins
Literature reports
1 report — tap to read
a) Patients undergoing percutaneous coronary intervention (PCI) with high on-treatment platelet reactivity (HPR; defined as 20 micromoles adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA) greater than 50%) received chronic atorvastatin 10 mg daily and clopidogrel 75 mg daily and then were randomly assigned to receive 15 days of either rosuvastatin 10 mg (n=25) or pravastatin 20 mg (n=25) daily instead of atorvastatin. After switching statins, MPA levels after stimuli with 20 and 5 micromolar ADP decreased by 6.6% (95% CI, 3.2%% to 10.1%; p less than 0.001) in the rosuvastatin group and by 6.3% (95% CI, 2.5 to 10.2%; p=0.002) in the pravastatin group and the prevalence of HPR decreased by 24% (p less than 0.001) 1.
Common questions
Can I take Clopidogrel and Simvastatin together?
Decreased formation of clopidogrel active metabolite resulting in high on-treatment platelet reactivity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clopidogrel and Simvastatin interaction?
It is rated moderate. Can be significant — usually manageable with 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 "established". Well documented — supported by controlled studies or strong clinical data.
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 Simvastatin 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 anything you'd monitor while I'm on both?
References (1)
- Park Y, Jeong YH, Tantry US, et al: Accelerated platelet inhibition by switching from atorvastatin to a non-CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study. Eur Heart J 2012; 33(17):2151-2162. PubMed
Keep reading about Clopidogrel
Keep reading about Simvastatin
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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