FDA Warns of Risks Associated With Simvastatin

There is an increased risk of muscle injury in patients taking the highest approved dose of simvastatin compared to patients taking lower doses of the drug -- which is marketed as Zocor -- or other statins, according to a March 19 FDA safety alert.

Although myopathy is a known side effect of statin medications, the FDA said patients taking an 80 mg dose of simvastatin are at increased risk. In addition, the risk increases when simvastatin, especially at higher doses, is used with certain other drugs. Symptoms of myopathy include muscle pain, tenderness or weakness, and an elevation of the enzyme creatine kinase in the blood.

Patients with rhabdomyolysis, the most serious form of myopathy, may have dark or red urine and fatigue in addition to muscle symptoms, the FDA said. Rhabdomyolysis, which is a rare adverse event reported with all statins, also can lead to kidney damage, kidney failure and death. Patients who are 65 years and older or who have hypothyroidism or poor kidney function are at increased risk for rhabdomyolysis.

The FDA advised patients to contact their physicians if they experience any of the aforementioned symptoms. Patients should not stop taking simvastatin unless instructed to do so by their physician.

A review of prescription drug use data by the FDA found that despite dose limitations and interaction precautions included on the simvastatin drug label, physicians are prescribing higher doses of simvastatin with other medications that are known to increase the risk for rhabdomyolysis.

Physicians should consider potential risks and benefits of simvastatin compared to other cholesterol-lowering therapies when prescribing the drug, said the FDA. Physicians also should review patients' medications for potential drug interactions before prescribing simvastatin.

The agency also noted that simvastatin should not be used in combination with

Furthermore, the FDA said no more than 10 mg of simvastatin should be used with

No more than 20 mg of simvastatin should be used with amiodarone, which is marketed as Cordarone, and verapamil, which is marketed as Isoptin, Verelan, Verelan PM, Calan, Bosoptin and Covera-HS, according to the FDA. In addition, no more than 40 mg of simvastatin should be used with diltiazem, which is marketed as Cardizem, Dilacor and Tiazac.

Finally, the FDA recently approved a labeling revision for simvastatin based on interim results from an ongoing clinical trial. Patients of Chinese descent should not receive simvastatin 80 mg with cholesterol-modifying doses of niacin-containing products.
The revised label recommends caution when these patients are treated with simvastatin 40 mg or less in combination with cholesterol-modifying doses of niacin-containing products.

Physicians are asked to report any adverse events associated with the use of simvastatin to the FDA's MedWatch program.