FDA: High-dose simvastatin increases risk of muscle injury - caution with lower doses plus Amiodarone, Verapamil, Diltiazem

Based on review of data from a large clinical trial and data from other sources, the U.S. Food and Drug Administration (FDA) is informing the public about an increased risk of muscle injury in patients taking the highest approved dose of the cholesterol-lowering medication, Zocor (simvastatin) 80 mg, compared to patients taking lower doses of simvastatin and possibly other drugs in the "statin" class.

The muscle injury, also called myopathy, is a known side effect with all statin medications. The most serious form of myopathy is called rhabdomyolysis. Patients with myopathy generally have muscle pain, tenderness or weakness, and an elevation of a muscle enzyme in the blood (creatine kinase). The higher the dose of statin used, the greater the risk of developing myopathy. The risk of myopathy is also increased when simvastatin, especially at the higher doses, is used with certain drugs (see Simvastatin Dose Limitations below).

The data come from the SEARCH study, in which myopathy was seen in nearly 1% of patients taking the 80 milligram dose of Zocor but in only 0.02% of patients taking the 20 milligram dose of Zocor.

Update 6/2011: FDA Restricts Use of Simvastatin 80 mg, due to increased risk of muscle damage http://goo.gl/K9O5v

Rhabdomyolysis was rare in the SEARCH study. It happened in only 11 of 6,031 patients (0.02%) in group taking the 80 milligram dose of Zocor, but was not seen in patients taking the 20 milligram dose.

New data also suggest that people of Chinese descent should not take Zocor at the 80 milligram dose -- and should be careful even when taking lower doses -- if they also take niacin-containing products.

Simvastatin Dose Limitations

These limitations apply to ALL patients taking simvastatin.

Do not use simvastatin with these medications:

Itraconazole
Ketoconazole
Erythromycin
Clarithromycin
Telithromycin
HIV protease inhibitors
Nefazodone

Do not use more than 10mg of simvastatin with these medications:

Gemfibrozil
Cyclosporine
Danazol

Do not use more than 20mg of simvastatin with these medications:

Amiodarone
Verapamil

Do not use more than 40mg of simvastatin with this medication:

Diltiazem

References:

FDA Drug Safety Communication: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. FDA.
FDA Warns of Zocor Risk to Muscles. WebMD.

FDA Restricts Use of Simvastatin 80 mg, due to increased risk of muscle damage http://goo.gl/K9O5v

Image source: Simvastatin. Wikipedia, public domain.