{"id":8775,"date":"2011-06-15T18:58:56","date_gmt":"2011-06-15T22:58:56","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?p=8775"},"modified":"2011-07-19T17:44:22","modified_gmt":"2011-07-19T21:44:22","slug":"nejm-fda-officials-explain-the-new-simvastatin-label","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2011\/06\/15\/nejm-fda-officials-explain-the-new-simvastatin-label\/","title":{"rendered":"NEJM: FDA Officials Explain the New Simvastatin Label"},"content":{"rendered":"

In a perspective published in the New England Journal of Medicine<\/em><\/a>, two FDA officials, Amy Egan and Eric Colman, explain in some detail the recent changes made by the FDA regarding simvastatin. They note that in the SEARCH trial, myopathy developed in 52 (0.9%) patients in the 80-mg group compared with only 1 (0.02%) patient in the 20-mg group. There were 22 cases of rhabdomyolysis with the high dose versus no cases with the low dose. Further, patients at high risk usually developed myopathy early in the course of treatment.<\/p>\n

In addition, because simvastatin is “particularly prone to drug-drug interactions,” the risk for myopathy is increased in patients taking high-dose simvastatin who are also taking other drugs, including several commonly used cardiovascular drugs such as amiodarone, diltiazem, and amlodipine.<\/p>\n

Finally, the FDA authors summarize data from adverse event reports from all the statins, noting that rates of fatal rhabdomyolysis have been higher with simvastatin 80 mg than with atorvastatin 80 mg or rosuvastatin 40 mg.<\/p>\n

The following chart provides a summary of the FDA action:
\n<\/a><\/p>\n\n\n\n\n\n\n\n\n\n
Key Components of Recent Safety-Labeling Changes for Simvastatin<\/strong><\/td>\n<\/tr>\n
1. Use of the 80-mg dose of simvastatin should be restricted to patients who have been taking it for a long time (e.g., 12 months or more) without signs or symptoms of clinically significant toxic effects on muscle. <\/p>\n

2. Patients who are currently taking an 80-mg dose of simvastatin without adverse effects but who need to begin taking an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for a drug\u2013drug interaction.<\/p>\n

3. Patients in whom the LDL cholesterol goal cannot be achieved with a 40-mg dose of simvastatin should instead be given other appropriate LDL cholesterol\u2013lowering therapy (e.g., a more potent statin that poses a lower risk of myopathy, such as atorvastatin or rosuvastatin).<\/td>\n<\/tr>\n

Drug Interactions Associated with Increased Risk of Myopathy and Rhabdomyolysis<\/strong><\/td>\n<\/tr>\n
 <\/p>\n

Interacting Agents<\/strong><\/p>\n

 <\/p>\n

Itraconazole<\/p>\n

Ketoconazole<\/p>\n

Posaconazole<\/p>\n

Erythromycin<\/p>\n

Clarithromycin<\/p>\n

Telithromycin<\/p>\n

HIV protease inhibitors<\/p>\n

Nefazodone<\/p>\n

Gemfibrozil<\/p>\n

Cyclosporine<\/p>\n

Danazol<\/td>\n

 <\/p>\n

Prescribing Recommendations<\/strong><\/p>\n

 <\/p>\n

Contraindicated with simvastatin<\/td>\n<\/tr>\n

 <\/p>\n

Amiodarone<\/p>\n

Verapamil<\/p>\n

Diltiazem<\/td>\n

 <\/p>\n

Do not exceed 10 mg of simvastatin daily<\/td>\n<\/tr>\n

 <\/p>\n

Amlodipine<\/p>\n

Ranolazine<\/td>\n

 <\/p>\n

Do not exceed 20 mg of simvastatin daily<\/td>\n<\/tr>\n

 <\/p>\n

Grapefruit juice<\/td>\n

 <\/p>\n

Avoid large quantities of grapefruit juice<\/p>\n

(>1 qt daily)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

In a perspective published in the New England Journal of Medicine, two FDA officials, Amy Egan and Eric Colman, explain in some detail the recent changes made by the FDA regarding simvastatin. They note that in the SEARCH trial, myopathy developed in 52 (0.9%) patients in the 80-mg group compared with only 1 (0.02%) patient […]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,7],"tags":[],"class_list":["post-8775","post","type-post","status-publish","format-standard","hentry","category-general","category-prevention"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/8775","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=8775"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/8775\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=8775"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=8775"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=8775"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}