Merck announces changes to high-dose simvastatin prescribing information in the U.S.

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced changes to the prescribing information in the United States for the highest dose of simvastatin, 80 mg, and the use of simvastatin with certain other medicines. Simvastatin is a cholesterol-lowering medicine developed by Merck (marketed as ZOCOR^®) that is now widely available in generic form; simvastatin is also a component of VYTORIN^® (ezetimibe/simvastatin), another cholesterol-lowering medicine from Merck. The revised U.S. prescribing information for ZOCOR and VYTORIN reflecting the changes regarding the 80 mg dose of simvastatin and the drug interaction updates are posted at www.merck.com.

The changes follow a U.S. Food and Drug Administration (FDA) review, announced by the agency in March 2010, of the risk of muscle injury (called myopathy, including its most serious form, rhabdomyolysis) with the highest dose of simvastatin. Merck has updated the U.S. prescribing information:

• To limit the use of the high dose of simvastatin, 80 mg, which is taken by approximately 12 percent of U.S. simvastatin users, to patients who have been taking that prescribed amount chronically (e.g., for 12 months or more) without evidence of muscle toxicity; and, in addition,
• To contraindicate and/or limit the dose of simvastatin when used with certain drugs where the combined use may increase the risk of myopathy and rhabdomyolysis.

These updates are described further below.

"Nothing is more important to Merck than the safety of our medicines and the well-being of the patients who take them," said Michael Rosenblatt, M.D., chief medical officer for Merck. "We are proud of the role that simvastatin plays along with a healthy diet for patients with high cholesterol and those at high risk for heart attacks and strokes. Many people who take simvastatin will not be affected by these label updates. We encourage those who think these changes might affect them to talk to their doctor. Patients should talk with their doctor before they stop taking any of their medicines. We are committed to communicating these changes to help physicians and their patients understand the updated recommendations for use of this important medicine."

As part of that commitment, Merck has launched a new website, www.simvastatininfocenter.com, with information for patients on these updates.

Prescribing information for ZOCOR has included information about the risk of myopathy and rhabdomyolysis since the initial approval of the medicine in 1991 and has described the dose-related nature of this risk since 2002. The FDA's review concluded that there is an increased risk of myopathy, including rhabdomyolysis, with simvastatin 80 mg compared with other statin therapies that can provide similar or greater reduction in LDL cholesterol and compared with lower doses of simvastatin. This increased risk is highest during the first year of treatment and then notably decreases.

In addition to limiting use of the 80 mg dose, the updated U.S. prescribing information modifies limitations on concomitant use of simvastatin with certain drugs:

• the use of simvastatin is contraindicated with certain azole antifungals and antibiotics, with HIV protease inhibitors, and with the drugs nefazodone, gemfibrozil, cyclosporine, and danazol; and
• the maximum recommended doses of simvastatin have been revised when used with amiodarone, ranolazine, and the calcium channel blockers verapamil, diltiazem and amlodipine.

Merck will be communicating to physicians about the changes, and also will communicate with managed care organizations and others to support efforts to implement the revised recommendations for use.