FDA Restricts Use of Simvastatin 80 mg
June 8, 2011 (Silver Spring, Maryland) ”” The Food and Drug Administration is recommending that physicians restrict prescribing high-dose simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage . The new FDA drug safety communication, issued today, states that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.
“Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug,” the agency states.
In addition, the FDA is requesting that additional changes be made to the drug’s label. The label will be changed to include the new dosing recommendations, as well as warnings not to use the drug with various medications, including itraconazole(Sporanox, Jannsen Pharmaceutica), ketoconazole (Nizoral by Ortho-McNeil Pharmaceutical), posaconazole (Noxafil, Merck), erythromycin, clarithromycin, telithromycin (Ketek, Sanofi-Aventis), HIV protease inhibitors, nefazodone,gemfibrozil, cyclosporine, and danazol.
In addition, the 10-mg dose should not be exceeded in patients taking amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc, Pfizer) and ranolazine (Ranexa, Gilead).
The changes to the label are based on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire . In that trial, 52 patients taking the 80-mg dose developed myopathy compared with one patient treated with the 20-mg dose. In addition, 22 patients treated with the high dose of simvastatin developed rhabdomyolysis compared with none treated with the 20-mg dose.
The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year and that older age and female sex increased the risks.
In statement released today following the FDA alert , Merck notes that it has launched a new information website and is encouraging patients who think the prescribing changes might affect them to speak with their doctors.
Dr Steven Nissen (Cleveland Clinic, OH), who wrote an editorial accompanying the 2004 publication of the A to Z trial, a study that tested high-dose simvastatin in acute coronary syndrome patients, who was critical of the high rate of myopathy in that study, called the FDA decision “appropriate” but said it comes late.
“Most knowledgeable lipid experts stopped administering the 80-mg dosage of simvastatin years ago,” he said in an email toheartwire . “Unfortunately, once again the FDA has been too slow to react to a serious drug safety problem. We currently have more than two million Americans taking an unsafe dosage of simvastatin when there are safer alternatives. I’m glad the FDA acted but wish they hadn’t taken so long.”
- Food and Drug Administration. FDA drug safety communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. June 8, 2011. Available here.
- Merck. US prescribing information for simvastatin revised to include new limits on the use of the highest dose–80 mg–and updated drug interaction information [press release]. June 8, 2011. Available here.
FDA Warns of Serious Risks Associated With Liraglutide
June 13, 2011 (updated June 24, 2011) ”” The US Food and Drug Administration (FDA) today warned healthcare professionals to closely monitor patients with diabetes receiving liraglutide injections (Victoza, Novo Nordisk) for thyroid C-cell tumors and acute pancreatitis.
Novo Nordisk said in a letter that a recent assessment showed that some primary care providers are not fully aware that use of liraglutide is associated with serious risks, which were known at the time of the drug’s approval in January 2010. Today’s warning is part of an ongoing risk evaluation and mitigation strategy (REMS) to “ensure that the benefits of the drug outweigh the risk,” according to the FDA.
Liraglutide is the first once-daily human glucagon-like peptide 1 analog indicated for the treatment of type 2 diabetes. The treatment is indicated in conjunction with diet and exercise to improve blood glucose control in adults with type 2 diabetes failing first-line therapy.
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both sexes of rats and mice, according to an alert sent today from MedWatch, the FDA’s safety information and adverse event reporting system. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans, as human relevance could not be ruled out by clinical or nonclinical studies. In addition, in clinical trials studying liraglutide, there were more cases of pancreatitis in patients treated with liraglutide than in patients treated with comparable medications.
The FDA recommends that patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinologist for further evaluation.
Although routine monitoring of serum calcitonin is of uncertain value in patients treated with liraglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation, the FDA said.
Both after initiation of liraglutide therapy and after dose increases, the FDA urges physicians to observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting).
The FDA is requiring a cardiovascular safety study to specifically evaluate the safety of liraglutide in a higher-risk population. The company also is required to conduct a 5-year epidemiologic study using a health claims database to evaluate thyroid and other cancer risks in addition to risks for hypoglycemia, pancreatitis, and allergic reactions.
Adverse events related to liraglutide should be reported to MedWatch by telephone at 1-800-332-1088, by fax at 1-800-332-1078, online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm, or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20857.