Simvastatin and Dronedarone: 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
Dronedarone
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.
Taking dronedarone (Multaq) with simvastatin needs some care. Dronedarone slows down the body system that normally breaks down simvastatin. That means more simvastatin can build up in your blood than expected.
When simvastatin levels get too high, it raises the chance of muscle problems. Watch for unusual muscle pain, tenderness, or weakness, especially if it comes with dark or brown urine. In rare cases this muscle damage can get serious.
The good news: this is very manageable. Your care team often keeps the simvastatin dose low (usually no more than 10 mg a day) when it is used with dronedarone. Please don't change anything on your own, just check with your pharmacist or doctor about your dose.
Interaction: Dronedarone increases simvastatin exposure via inhibition of CYP3A4-mediated metabolism and P-gp-mediated efflux, raising the risk of myopathy and rhabdomyolysis.
- Magnitude: Dronedarone 400 mg BID + simvastatin 40 mg QD x14 days increased simvastatin AUC ~3.9-fold and Cmax ~3.75-fold; simvastatin acid AUC ~1.96-fold, Cmax ~2.14-fold.
- Direction: Increased simvastatin effect/toxicity (neither drug is a prodrug in the relevant sense).
- Evidence: Probable; severity major.
- Management: If coadministration is necessary, limit simvastatin to no more than 10 mg/day. Monitor for muscle symptoms and consider CK if symptomatic.
What happens
Increased simvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Deep Dive
Taking dronedarone together with simvastatin 40 mg orally once daily produced a marked rise in both the Cmax and AUC of simvastatin 3. This combination may heighten the likelihood of myopathy and rhabdomyolysis 1. If the two drugs must be given together, simvastatin should be capped at a maximum of 10 mg/day 132. A drug interaction study in which dronedarone 400 mg BID was administered with simvastatin 40 mg QD over 14 days showed that the AUC of simvastatin and of its active metabolite simvastatin acid rose by factors of 3.90 and 1.96, while their Cmax values increased by 3.75 and 2.14, respectively 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated simvastatin metabolism; inhibition of P-gp-mediated efflux transport of simvastatin metabolism
How to manage this interaction
This interaction is manageable with the right dose and monitoring.
- Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- When these two are used together, care teams typically limit the simvastatin dose to no more than 10 mg per day to reduce risk.
- Your team may monitor you more closely for muscle-related side effects.
- Report any unexplained muscle pain, tenderness, weakness, or dark urine to your pharmacist or doctor promptly.
- Ask your pharmacist or prescriber to confirm your simvastatin dose is appropriate with dronedarone, or whether a different statin may suit you better.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Simvastatin and Dronedarone together?
Dronedarone raises simvastatin levels and the risk of muscle damage, so if the two are used together the simvastatin dose is usually kept at no more than 10 mg per day. Don't change anything yourself; confirm your dose with your pharmacist or doctor and report any muscle pain. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Dronedarone 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 is the Simvastatin and Dronedarone interaction managed?
This interaction is manageable with the right dose and monitoring. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. When these two are used together, care teams typically limit the simvastatin dose to no more than 10 mg per day to reduce risk. Your team may monitor you more closely for muscle-related side effects. Report any unexplained muscle pain, te… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Simvastatin or Dronedarone 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 (3)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Product Information: MULTAQ(R) oral tablets, dronedarone oral tablets. sanofi-aventis US LLC (per manufacturer), Bridgewater, NJ, 2017. DailyMed
Keep reading about Dronedarone
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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