The highest approved dose (80 mg) of the cholesterol-lowering drug simvastatin, is tied to higher risk of myopathy or muscle injury, including its most serious form rhabdomyolysis. This is particularly significant in the first 12 months of use, said the US Food and Drug Administration (FDA), who announced safety label changes yesterday. Patients are advised not to stop their medication without first talking to their doctor.

Merck (known as MSD outside the United States and Canada), market simvastatin in the US as the brand Zocor, and in combinaton with another cholesterol-lowering drug ezetimibe, as Vytorin. It is also available with niacin as Abbott’s Simcor and as a single-ingredient generic drug.

About 12% of Americans who take simvastatin in its various forms are on the 80 mg dose, prescriptions for which were issued for. 2.1 million US patients in 2010.

The FDA approved simvastatin under the brand name Zocor in 1991, for use with diet and exercise to reduce the level of LDL-cholesterol (LDL-C, low-density lipoprotein cholesterol), in the blood. High levels of this “bad” cholesterol have been linked to a higher risk of heart attack, stroke and death from cardiovascular causes.

The agency approved the highest dose, 80 mg, in 1998, and a generic version has been available since 2006. Today, estimates suggest the vast majority of Americans who take simvastatin are on on the generic version.

“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,” said Dr Eric Colman, FDA’s deputy director of the Division of Metabolism and Endocrinology Products at the agency’s Center for Drug Evaluation and Research.

The decision follows the FDA’s review of trial data and analyses of adverse events received via its reporting system.

“All showed that patients taking simvastatin 80 mg daily had an increased risk of muscle injury compared to patients taking lower doses of simvastatin or other statin drugs,” said the FDA’s announcement.

The risk of muscle injury is highest during the first year of taking the highest dose, they added, explaining however, that this was mostly as a result of interaction with other drugs, and frequently linked with a genetic predisposition for muscle injury associated with the drug.

The highest dose should no longer be prescribed for new patients, said the FDA.

If the lower 40 mg dose simvastatin is not enough to help patients lower their LDL-C, doctors should not prescribe the 80 mg dose, but instead, put them on another LDL-C reducing drug, they added.

The new label changes will reflect that the FDA recommends the 80 mg dose of simvastatin is only used for patients who have been taking this highest dose for 12 months or more and who have not shown signs or developed symptoms of muscle toxicity.

Where relevant, they will also include contraindications and dose limits for when the patient is also taking other drugs that interact to increase the level of simvastatin in the body, which can increase the risk for muscle injury.

In a press statement Merck said they have updated the US prescribing information.

Their chief medical officer, Dr Michael Rosenblatt, said:

“Many people who take simvastatin will not be affected by these label updates.”

He said patients who think these changes may apply to them should go and see their doctor.

“Patients should talk with their doctor before they stop taking any of their medicines,” he cautioned.

Merck have launched a new website, http://www.simvastatininfocenter.com, to inform patients about the changes.

Sources: FDA, Merck.

Written by: Catharine Paddock, PhD