A recommendation against prescribing the highest available dose of simvastatin is among the changes in the labeling information for the drug, the Food and Drug Administration announced on June 8.
The 80-mg dose of simvastatin has been associated with an elevated risk of myopathy, particularly during the first 12 months of treatment, so the FDA is now recommending that this dose be used only for patients who have been taking this dose for 12 months or longer and have not had any signs of myopathy, according to a statement issued by the agency.
The increased risk of myopathy with this dose is also often related to interactions with some medications and a genetic predisposition towards simvastatin-related myopathy, the statement said.
The FDA is also advising health care professionals not to start new patients on this dose and to prescribe alternative LDL cholesterol–lowering drugs for patients who do not meet their LDL-cholesterol goal on the 40-mg dose of simvastatin.The 80-mg dose lowers LDL cholesterol by an additional 6% over the 40-mg dose, the statement said.
The 80-mg dose is the highest dose approved for simvastatin, which is marketed as Zocor and is also available in generic formulations. Simvastatin is also available in combination with ezetimibe (Vytorin) and in combination with niacin (Simcor).
"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," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research said in the statement.
The changes are based on the FDA’s review of a 7-year study that found a greater risk of myopathy and rhabdomyolysis (none were fatal) among MI survivors who were treated with 80 mg of simvastatin, compared with those on the 20-mg dosage, and adverse events reported to the FDA’s MedWatch program. In the study, the risk of myopathy was highest during the first 12 months of treatment; an older age, female gender, concomitant use of a calcium channel blocker (Diltiazem in particular) and the presence of a genetic variant that increases plasma levels of simvastatin were also associated with a greater risk of myopathy, defined as unexplained muscle weakness or pain and a serum creatine kinase 10 times the upper limit of normal (JAMA 2004;292:2585-90).
Among the MedWatch reports, there was a higher rate of fatal rhabdomyolysis with the 80-mg dose, compared with lower doses of simvastatin and with other statins.
The recommendations have been incorporated into the label of these products, including the contraindications section. About 2.1 million patients in the United States were prescribed a product that contained 80 mg of simvastatin in 2010, according to the FDA.
The FDA statement is available at www.fda.gov/Drugs/DrugSafety/ucm256581.htm.
Adverse events associated with products that contain simvastatin should be reported online at the FDA’s MedWatch program or by phone at 800-332-1088.