Amlodipine increases simvastatin blood levels, raising the risk of myopathy and rhabdomyolysis. The FDA has set a maximum simvastatin dose of 20 mg daily for patients taking amlodipine. Higher simvastatin doses with amlodipine have been associated with an unacceptable risk of muscle damage.
How This Interaction Works (Mechanism)
Amlodipine inhibits CYP3A4, the enzyme primarily responsible for simvastatin metabolism. This increases simvastatin's area under the curve (AUC) by approximately 70 to 80 percent. Higher circulating levels of simvastatin and its active acid metabolite increase the risk of dose-dependent myotoxicity. The mechanism of statin-induced muscle damage involves mitochondrial dysfunction and depletion of coenzyme Q10 in skeletal muscle fibers.
Source: FDA Drug Safety Communication on Simvastatin Dose Limitations, 2011 (reaffirmed 2024)
Do not exceed 20 mg of simvastatin daily when taking amlodipine. If higher statin doses are needed for cholesterol management, switch to a statin that is not metabolized by CYP3A4, such as rosuvastatin or pravastatin. Report any muscle pain, tenderness, or weakness to your doctor promptly. The risk increases with age, female sex, and renal impairment.
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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
Amlodipine and Simvastatin have a moderate interaction that requires caution. While some patients may take both under medical supervision, the combination can cause adverse effects. Talk to your doctor before combining these medications, and do not adjust doses on your own.
Amlodipine increases simvastatin blood levels, raising the risk of myopathy and rhabdomyolysis. The FDA has set a maximum simvastatin dose of 20 mg daily for patients taking amlodipine. Higher simvastatin doses with amlodipine have been associated with an unacceptable risk of muscle damage.
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 Amlodipine and Simvastatin combination is safe for you, or whether adjustments are needed.
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