Simvastatin and Amiodarone: 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
Amiodarone
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.
Let's talk about taking amiodarone (for your heart rhythm) together with simvastatin (for cholesterol). Amiodarone slows down the liver enzyme that normally clears simvastatin from your body. That means more simvastatin builds up than it should.
The main worry with too much simvastatin is muscle problems, things like muscle pain, tenderness, or weakness. In rare cases this can become serious and affect the kidneys. The good news is your care team knows about this pairing and manages it every day, usually by keeping your simvastatin dose lower and watching how your muscles feel. If you notice new muscle aches or weakness, let your doctor or pharmacist know so they can help.
Effect: Amiodarone inhibits CYP3A4, reducing simvastatin metabolism and increasing simvastatin exposure (AUC/Cmax), which raises the risk of myopathy and rhabdomyolysis. Direction is increased statin effect/toxicity; onset rapid; evidence established.
- Dose cap: Do not exceed simvastatin 20 mg daily with concomitant amiodarone.
- Monitor: Muscle pain, tenderness, weakness; check CK if symptomatic. Discontinue if CK markedly elevated or myopathy/rhabdomyolysis is suspected or diagnosed.
- Alternative: Consider a non-CYP3A4 statin such as pravastatin.
Early cessation of one or both agents may halt and potentially reverse rhabdomyolysis progression.
What happens
Increased exposure to simvastatin and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Cases of myopathy and rhabdomyolysis have occurred in patients taking simvastatin together with amiodarone3. One suggested mechanism for this interaction is that amiodarone inhibits the CYP3A4-mediated metabolism of simvastatin 4. When amiodarone is given concurrently, simvastatin should be kept at no more than 20 mg per day 1. Watch for signs and symptoms indicative of myopathy or rhabdomyolysis. Track creatine kinase (CK) levels, and stop therapy if there is a pronounced rise in CK or if myopathy or rhabdomyolysis is either diagnosed or suspected. Stopping amiodarone, simvastatin, or both may arrest and potentially reverse the course of rhabdomyolysis when caught early. As another option, simvastatin can be replaced with a different HMG-CoA inhibitor, for example pravastatin, which does not undergo CYP3A4 metabolism 4. 3.
Why it happens (mechanism)
Inhibition by amiodarone of CYP3A4-mediated simvastatin metabolism
How to manage this interaction
This is a well-recognized combination that your care team can manage safely.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team will typically cap simvastatin at 20 mg daily when you are also on amiodarone.
- They may monitor you more closely, including a blood test (creatine kinase) if muscle symptoms appear.
- Sometimes a different statin that isn't affected the same way, such as pravastatin, is a good alternative. That decision is individualized by your prescriber.
Call your pharmacist or doctor promptly if you notice new muscle pain, tenderness, weakness, or dark urine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) In a pharmacokinetic study, simvastatin exposure rose when simvastatin and amiodarone were given together. Participants took amiodarone 400 mg once daily for 3 days, and on day 3 a single 40-mg dose of simvastatin was given. For simvastatin, the mean ratio (with amiodarone/without amiodarone) was 1.76 for AUC and 1.79 for Cmax. The corresponding ratios for simvastatin acid (the beta-hydroxyacid of simvastatin) were 1.75 for AUC and 1.72 for Cmax 1.
b) Between January 2003 and January 2008, 52 cases of rhabdomyolysis linked to concurrent simvastatin and amiodarone use were reported to the US Food and Drug Administration adverse events reporting database. Patients ranged in age from 50 to 88 years (median age, 73), with 71% male and 19% female. Gender was not reported for 10% of patients. Amiodarone was given alongside a simvastatin dose of 80 mg (50% of patients), 40 mg (25%), 20 mg (8%), and 5 mg (2%). Thirty-seven (71%) patients reported concurrent medications including gemfibrozil, clarithromycin, protease inhibitors, angiotensin-converting enzyme inhibitors, and atorvastatin. In 42% of patients, rhabdomyolysis appeared within 2 months of starting amiodarone and simvastatin therapy (mean onset 5 months), although time to onset was not reported for 40% of patients. Hospitalization was needed in 92% of patients, and 25% of cases were regarded as life-threatening. It was observed that 10% of patients who developed rhabdomyolysis became disabled. One death was reported. Symptoms and laboratory values tended to improve once one or both agents were stopped 3.
c) A 72-year-old man developed rhabdomyolysis, along with renal failure and possible hepatotoxicity, after simvastatin 80 milligrams/day (mg/day) was added to an established regimen of amiodarone 200 mg/day, which had been started following coronary artery bypass. The patient had a history of diabetes, hypertension, hyperlipidemia, and mild azotemia, and had previously taken pravastatin 20 to 40 mg/day and fluvastatin 40 to 80 mg/day without adverse effects. About 1 month after simvastatin was started, the patient developed thigh weakness, achiness, and dark urine. Laboratory testing showed an elevated CK level of 19,620 units/liter (reference range 60 to 224 units/liter), an AST level of 912 units/liter (30 to 60 units/liter), an ALT level of 748 units/liter (30 to 60 units/liter), and markedly elevated serum and urine myoglobin levels. In addition, serum creatinine (2.6 mg/dL or 230 mcmol/L) and BUN (50 mg/dL or 18 mmol/L) were elevated, and the 24-hour urine protein level was 549 mg. Both simvastatin and amiodarone were stopped at once, and the patient received hydration with forced alkaline diuresis. After 13 days, hepatic enzyme levels fell substantially, and 3 months later ALT, AST, and CK levels were 49, 32, and 640 units/liter, respectively. Inhibition of CYP3A4-mediated simvastatin metabolism by amiodarone was suggested as a possible mechanism for this interaction 4.
d) A 63-year-old man developed rhabdomyolysis after amiodarone (1 gram/day for 10 days, then 200 milligrams (mg)/day) was added to an established treatment regimen that included simvastatin 40 mg daily. About 11 days after amiodarone therapy began, the patient showed signs of rapid exertional exhaustion, followed 5 days later by complaints of diffuse muscle pain and generalized weakness. Laboratory testing revealed a creatine phosphokinase (CK) serum concentration of 18,852 units/liter, with aspartate aminotransferase and lactic dehydrogenase serum concentrations of 438 units/liter and 807 units/liter, respectively. Despite discontinuation of simvastatin, serum CK continued to climb, peaking at 40,392 units/liter 3 days later. Amiodarone and phenprocoumon were both stopped and pravastatin 20 mg daily was substituted for simvastatin, after which the patient's serum CK fell to within normal limits and muscle strength slowly improved. The case study authors assigned the proposed interaction a Naranjo causal probability relationship of 'probable' 5.
e) A 72-year-old man receiving simvastatin together with amiodarone and atazanavir experienced rhabdomyolysis and acute renal failure. He presented with a 4-day history of generalized pain, weakness, and fatigue, and a 3-day history of dark orange urine. He had been taking atorvastatin 40 mg daily for 2 years and was switched to simvastatin 80 mg 27 days before this presentation. In addition, amiodarone 400 mg daily was started 19 days before this presentation and then reduced to 200 mg daily after 7 days. His other chronic medications included atazanavir, stavudine, and delavirdine, all taken for 2 years. Laboratory results showed a creatine kinase level of 66,680 units/liter, nearly 300 times the upper limit of normal. The patient was diagnosed with rhabdomyolysis and oliguric acute renal failure. Simvastatin, amiodarone, and the HIV medications were all temporarily stopped, and the patient received forced alkaline diuresis and dialysis. He was discharged on day 9 (creatine kinase level, 1695 units/liter), restarted on amiodarone, and continued outpatient dialysis for one month. His HIV medications were resumed after 6 weeks, but the statin was not restarted. This patient had additional risk factors of advanced age and concurrent atazanavir use, in which atazanavir may have contributed by further reducing simvastatin's metabolism. The Naranjo adverse drug event probability scale indicated a "probable" rating that the effects were due to an interaction between simvastatin and amiodarone/atazanavir 2.
Common questions
Can I take Simvastatin and Amiodarone together?
Amiodarone raises simvastatin levels and the risk of muscle injury, so simvastatin should not exceed 20 mg daily with amiodarone, and any new muscle pain or weakness should be reported right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Amiodarone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Simvastatin and Amiodarone interaction managed?
This is a well-recognized combination that your care team can manage safely. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team will typically cap simvastatin at 20 mg daily when you are also on amiodarone. They may monitor you more closely, including a blood test (creatine kinase) if muscle symptoms appear. Sometimes a different statin that isn't affected the… 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 Simvastatin or Amiodarone 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 (5)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Schmidt GA, Hoehns JD, Purcell JL, et al: Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. J Am Board Fam Med 2007; 20(4):411-416. PubMed
- US Food and Drug Administration: FDA Drug Safety Newsletter. US Food and Drug Administration. Rockville, MD. 2008.
- Ricaurte B, Guirguis A, Taylor HC, et al: Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother 2006; 40(4):753-757. PubMed
- Roten L, Schoenenberger RA, Krahenbuhl S, et al: Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother 2004; 38:978-981. DOI
Keep reading about Amiodarone
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist