FDA Recommends Dose Limitations for Zocor (simvastatin) To Reduce Muscle Injury

by Dr Sam Girgis on June 9, 2011

Zocor, generically known as simvastatin, is used by millions of people throughout the world to lower the levels of low density lipoprotein (LDL) cholesterol.  LDL cholesterol, known as the ‘bad’ cholesterol, contributes to the development of atherosclerosis which leads to heart attack and stroke.  In combination with diet and exercise, cholesterol lowering medications can decrease the risk of heart attack, stroke, and other cardiovascular diseases.  We have previously discussed recent results that caused the NIH to stop the AIM-HIGH clinical trial 18 months ahead of schedule because niacin did not show any benefit for heart disease patients.  On June 8, 2011, the Food and Drug Administration (FDA) released a drug safety communication and recommended limiting the use of the highest dose (80mg) of simvastatin because of the increased risk of muscle injury.  Simvastatin is also sold in combination with ezetimibe as Vytorin, and niacin as Simcor.  The FDA is estimating that about 2.1 million patients in the United States were prescribed a product containing 80mg of simvastatin in 2010.  The 80mg dose of simvastatin should only be used for those patients who have been taking it for over one year without signs of muscle damage.  New patients should not be started on 80mg of simvastatin.  In addition, the FDA is making changes to the drug label emphasizing that its use is contraindicated for use with certain medications.  Myopathy, or muscle pain, caused by simvastatin is characterized by tenderness, weakness, aches, and elevated blood levels of a muscle protein called creatine kinase (CK).  A more serious and sometimes fatal form of myopathy, known as rhabdomyolysis, can result from simvastatin use and results in the development of electrolyte abnormalities and kidney damage, which can progress to kidney failure requiring dialysis.  Patients who are currently taking the 80mg dose of simvastatin should not stop taking the medication until consulting with their physician.  In addition, they should report muscle pain, aches, tenderness, weakness, fatigue, and dark colored urine to their healthcare professional.  Physicians who have patients that are not meeting their cholesterol goals with 40mg of simvastatin should switch them to a different cholesterol lowering medication instead of increasing the dose to 80mg.  In addition, physicians who prescribe medications that interact with simvastatin should also switch their patients to different cholesterol lowering medications.  The FDA made the changes to their recommendations based on the results of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial.  The SEARCH trial was a seven year randomized double blind study comparing the efficacy and safety of 80mg of simvastatin to 20mg of simvastatin, with or without vitamin B12 and folate in patients who had heart attacks.  Fifty two patients in the 80mg group developed symptoms of myopathy.  In the 20mg group, only one patient developed symptoms of myopathy.  Twenty two patients in the 80mg group developed rhabdomyolysis, while none in the 20mg group developed the condition.  The risk of myopathy or rhabdomyolysis was highest in the first year, among females, in older patients, and in patients taking blood pressure medications of the calcium channel blocker class, particularly diltiazem.  Interestingly, a genetic variant of a liver transporter that is involved in the uptake of simvastatin was found in over 60% of patients with myopathy.  It is thought that this genetic variant transports less simvastatin into the liver, and thus causes elevated serum levels of simvastatin which raise the risk of myopathy.  Tests for this and other genetic variants may become routine, as the metabolism of these medications is better understood.  Many researchers and physicians have warned of the adverse effects of high doses of simvastatin and have stated that this dose limitation should have occurred many years ago.

For more information on Zocor (simvastatin), see Merck’s website on the drug.

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