Amiodarone significantly increases simvastatin blood levels, raising the risk of severe muscle damage (rhabdomyolysis) and kidney failure. The FDA has set a maximum simvastatin dose of 20 mg daily for patients taking amiodarone to reduce this risk.
How This Interaction Works (Mechanism)
Amiodarone is a potent inhibitor of CYP3A4, the primary enzyme responsible for simvastatin metabolism. This inhibition can increase simvastatin plasma levels by 100 to 200 percent, dramatically raising the risk of myopathy and rhabdomyolysis. Simvastatin's active metabolite (simvastatin acid) is particularly susceptible to CYP3A4 inhibition. Rhabdomyolysis involves the breakdown of skeletal muscle fibers, releasing myoglobin into the bloodstream, which can cause acute kidney failure.
Source: FDA Drug Safety Communication on Simvastatin Dose Limitations, 2011 (reaffirmed 2024)
Do not exceed 20 mg of simvastatin daily when taking amiodarone. Better yet, switch to a statin that is not metabolized by CYP3A4, such as pravastatin or rosuvastatin, which are not affected by amiodarone. Report any unexplained muscle pain, tenderness, weakness, or dark urine immediately. Regular creatine kinase (CK) monitoring may be warranted.
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Sources and standards behind this page
What a drug interaction does, and how strongly it is supported, is documented in public labeling and federal safety references rather than in any one summary, and the sources below are the primary ones. They are linked so a reader can check a claim without taking this page's word for it.
- DailyMed carries the current FDA labeling for every marketed drug product, including the warnings and drug interaction sections.
- Drugs@FDA is the federal database of approved drug products and their approval documents.
- FDA: Drug interactions, what you should know explains how drug-drug, drug-food and drug-condition interactions are described on labels.
- FDA Drug Safety Communications publishes the agency's safety alerts and label changes as they are issued.
- FDA MedWatch is the program for reporting and reviewing adverse events, including suspected interactions.
- openFDA provides public access to FDA labeling and adverse event data.
- MedlinePlus drug information is the National Library of Medicine's consumer reference for what a medicine is and how it is taken.
- NIAAA: Harmful interactions documents which medicines interact with alcohol and how.
- NCCIH: Herb-drug interactions summarises the evidence on interactions between herbal products and medicines.
- National Library of Medicine maintains the drug and health databases the sources above draw on.
This page describes how this interaction works and where it is documented. It is not medical advice: a prescriber or pharmacist decides what applies to a particular patient and medication.
Frequently Asked Questions
Simvastatin and Amiodarone have a severe interaction and should generally not be taken together without close medical supervision. The combination can cause serious, potentially life-threatening side effects. Contact your doctor immediately if you are currently taking both medications.
Amiodarone significantly increases simvastatin blood levels, raising the risk of severe muscle damage (rhabdomyolysis) and kidney failure. The FDA has set a maximum simvastatin dose of 20 mg daily for patients taking amiodarone to reduce this risk.
Yes. Anytime you are taking multiple medications, supplements, or substances, you should inform your doctor and pharmacist. They can evaluate your specific risk factors (age, kidney function, other medications, medical conditions) and determine whether the Simvastatin and Amiodarone combination is safe for you, or whether adjustments are needed.
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