Cilostazol and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cilostazol
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.
You've been prescribed cilostazol (Pletal), which helps blood flow in your legs, along with simvastatin (Zocor), a cholesterol medicine. Here's the simple version: cilostazol slows down the liver enzyme that normally clears simvastatin. That means more simvastatin can build up in your blood, roughly 1.5 to 1.8 times as much.
Higher simvastatin levels can raise the small chance of muscle problems, like unexplained aching, tenderness, or weakness. This is very manageable. Please tell your pharmacist or doctor you take both, and let them know right away if you notice new muscle pain. Your care team can adjust things and keep an eye on you.
Effect: Cilostazol (weak CYP3A4 inhibitor) reduces CYP3A4-mediated metabolism of simvastatin (CYP3A4 substrate), increasing exposure.
- Magnitude: Simvastatin Cmax up to 1.8-fold, AUC 1.6-fold; simvastatin acid Cmax 1.6-fold, AUC 1.3-fold.
- Direction: Increased simvastatin/simvastatin acid levels, raising risk of myopathy and rhabdomyolysis.
- Onset: Unspecified; evidence: established.
- Management: Monitor for muscle symptoms and CK if indicated. Statin dose may need to be individualized by the care team; consider alternatives per clinical judgment.
What happens
Increased simvastatin exposure
Interaction Deep Dive
When several oral doses of cilostazol were given alongside a single oral dose of simvastatin, the Cmax of simvastatin rose by as much as 1.8-fold, while the Cmax of the active metabolite simvastatin acid increased up to 1.6-fold. The AUC values showed comparable changes during cilostazol coadministration, rising 1.6-fold for simvastatin and 1.3-fold for simvastatin acid. This interaction reflects the fact that cilostazol acts as a weak CYP3A4 inhibitor2, whereas simvastatin serves as a CYP3A4 substrate. Because higher plasma concentrations of simvastatin and simvastatin acid heighten the likelihood of myopathy and rhabdomyolysis 1, this is clinically relevant.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of simvastatin by cilostazol
How to manage this interaction
Good news: this combination can be used safely with a little attention from your care team.
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise.
- Your simvastatin dose may be adjusted and individualized by your care team, since cilostazol raises its levels.
- Your team may monitor you more closely for muscle-related side effects.
- Report promptly any new muscle pain, tenderness, weakness, or dark urine.
- Ask your pharmacist before adding new medicines that also affect the same liver enzyme.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Administration of a single oral 40 mg dose of simvastatin on day 1, oral cilostazol 100 mg twice daily on days 2 through 5, and then a single dose of both cilostazol and simvastatin on day 6 to 17 healthy participants produced increases in the Cmax of simvastatin and simvastatin acid of 1.8-fold and 1.6-fold, respectively. The geometric least squares mean ratios of AUC (infinity) for simvastatin given together with cilostazol versus simvastatin given alone were 1.64 (90% CI, 1.38 to 1.95) for simvastatin and 1.31 (90% CI, 1.04 to 1.66) for simvastatin acid. No serious adverse effects were reported 2.
Common questions
Can I take Cilostazol and Simvastatin together?
Cilostazol raises simvastatin levels and slightly increases the chance of muscle side effects, so keep taking both as prescribed and tell your care team, reporting any new muscle pain right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cilostazol 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 is the Cilostazol and Simvastatin interaction managed?
Good news: this combination can be used safely with a little attention from your care team. Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Your simvastatin dose may be adjusted and individualized by your care team, since cilostazol raises its levels. Your team may monitor you more closely for muscle-related side effects. Report promptly any new muscle… Management is individual — always follow your own care team's guidance.
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 Cilostazol 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 (2)
Keep reading about Cilostazol
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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