The U.S. Food and Drug Administration today is announcing safety label changes for the cholesterol-lowering medication simvastatin" data-scaytid="1">simvastatin because the highest approved dose--80 milligram (mg)--has been associated with an elevated risk of muscle injury or myopathy, particularly during the first 12 months of use.
[12-15-2011] The U.S. Food and Drug Administration (FDA) is notifying the public that it has revised the dose limitation for the cholesterol-lowering drug simvastatin from 10 mg to 20 mg when it is co-administered with the cardiac drug amiodarone" data-scaytid="9">amiodarone. In June 2011, FDA previously recommended that the dose limitation for simvastatin be decreased from 20 mg to 10 mg, and has now reconsidered that recommendation.
In patients who are taking both simvastatin and amiodarone, the dose of simvastatin should not exceed 20 mg per day. The simvastatin drug labels (Zocor" data-scaytid="19">Zocor and generics, Vytorin" data-scaytid="23">Vytorin) have been updated to reflect this correction.
In June 2011, FDA restricted the use of the highest approved dose of simvastatin (80 mg) to reduce the risk of muscle injury (myopathy). Therefore the 40-mg dose became the maximum safe dose of simvastatin. At the same time, FDA also proportionally lowered (i.e., a 50% reduction or more) all the maximum safe doses of simvastatin when it is taken with certain interacting drugs (i.e., drugs that can raise simvastatin blood levels). However, the simvastatin dose limitation when taken with amiodarone (in which the simvastatin dose was lowered from 20 mg to 10 mg) was made in error. Unlike other interacting drugs, there were no pharmacokinetic or clinical trial data to support the simvastatin dose reduction approved with amiodarone. Therefore FDA has determined that the simvastatin dose limitation, when taken with amiodarone, should be restored to 20 mg. [End update]
The agency is recommending that simvastatin 80 mg be used only in patients who have been taking this dose for 12 months or more and have not experienced any muscle toxicity. It should not be prescribed to new patients. There are also new contraindications and dose limitations for when simvastatin is taken with certain other medications.
Simvastatin is used together with diet and exercise to reduce the amount of “bad cholesterol” (low-density lipoprotein cholesterol or LDL-C) in the blood. High levels of LDL-C are linked to a higher risk of heart attack, stroke and cardiovascular death. In 2010, about 2.1 million patients in the United States were prescribed a product containing simvastatin 80 mg.
“The FDA has completed its review of the safety of high-dose simvastatin and is making label changes to reduce the risk of statin-associated muscle injury,” said Eric Colman, M.D., deputy director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “We want to ensure that patients and health care professionals are aware of the new labeling changes to simvastatin, including the increased risk of myopathy when using the 80 mg dose of simvastatin.”
The changes to the label for simvastatin-containing medications are based on the FDA’s review of the results of the seven-year Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine clinical trial, other clinical trial data, and analyses of adverse events submitted to the FDA’s Adverse Event Reporting System. All showed that patients taking simvastatin 80 mg daily had an increased risk of muscle injury compared to patients taking lower doses of simvastatin or other statin drugs. The risk of muscle injury is highest during the first year of treatment with the 80 mg dose of simvastatin, is often the result of interactions with certain other medicines, and is frequently associated with a genetic predisposition for simvastatin-related muscle injury.
Simvastatin is sold under the brand-name Zocor and as a single-ingredient generic product. It is also sold in combination with ezetimibe as Vytorin and in combination with niacin as Simcor" data-scaytid="113">Simcor.
The FDA has revised the drug labels for simvastatin and Vytorin to include the new 80 mg dosing restrictions. The agency also revised the labels for simvastatin, Vytorin and Simcor to include new dosing recommendations when these drugs are used with certain medications that interact to increase the level of simvastatin in the body, which can increase the risk for myopathy. Patients who are unable to adequately lower their level of LDL-C on simvastatin 40 mg should not be given the higher 80 mg dose of simvastatin; instead, they should be placed on an alternative LDL-C-lowering treatment(s).
For more information:
- FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury
- FDA Consumer Update: Limit use of 80 mg simvastatin
- Previous FDA Drug Safety Communication: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury
- FDA Warns about Increased Risk of Muscle Injury with Zocor
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.