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.

Statins slightly increase risk of cataracts, liver dysfunction, kidney failure and muscle weakness

Statins do NOT prevent a long list of diseases

Statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.

Statins may decrease risk of esophageal cancer

Statin use was associated with decreased risks of oesophageal cancer.

Statins slightly increase the risk of liver dysfunction, kidney failure, muscle weakness and cataracts

Statin use was associated with increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract.

Is the risk the same with all statins?

Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin.

A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year.

How long does the risk last?

After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men.

What was the NNT and NNH?

Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 and for oesophageal cancer was 1266 and for men the respective values were 33 and 1082.

In women the NNH for an additional case of acute renal failure over five years was 434, of moderate or severe myopathy was 259, of moderate or severe liver dysfunction was 136, and of cataract was 33. Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91.

Conclusion

Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified.

Interestingly, the BMJ abstract did not mention increased diabetes risk that was reported in a previous study published in The Lancet.

References:

Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010; 340:c2197 doi: 10.1136/bmj.c2197 (Published 20 May 2010).

Balancing the intended and unintended effects of statins. BMJ 2010; 340:c2240 doi: 10.1136/bmj.c2240 (Published 20 May 2010).

People on statins are 9% more likely to develop diabetes according to a meta-analysis
Cholesterol drug side effects need watching: study. Reuters.

Image source: Simvastatin. Wikipedia, public domain.