The Food and Drug Administration (FDA) has released its findings of an analysis of 41 long-term, placebo-controlled clinical trials involving 64,000 patients treated with a statin (the class of drugs most commonly used to lower lipid levels) and 56,000 patients taking a placebo to determine whether there was a greater incidence of amyotrophic lateral sclerosis (ALS), known also as Lou Gehrig's disease, in the statin group. The FDA performed the analysis because it had received, through its Adverse Event Reporting System, more than expected reports of ALS cases in patients taking statins. But according to the agency's review, there was no greater incidence of ALS associated with the use of statins (4.2 cases per 100,000 patient-years among patients taking statins, compared with five cases per 100,000 patient-years among those taking a placebo). Statins are widely used, and in the next few months the FDA is expecting the results of an epidemiologic study of the association between their use and ALS conducted by Lorene Nelson of the Stanford University School of Medicine.

Health care professionals should be aware that the FDA continues to receive reports of rhabdomyolysis as a severe adverse effect in the use of simvastatin (Zocor) or in combination products containing it (simvastatin plus ezetimibe [Vytorin] and simvastatin plus niacin [Simcor]) when taken concurrently with the antiarrhythmic agent amiodarone (Cordarone, Pacerone).

Rhabdomyolysis is an acute, sometimes fatal disease in which there is direct injury to the plasma membrane of the skeletal muscle (as manifested by elevated levels of creatine kinase, also called creatine phosphokinase). The damage to the skeletal muscle precipitates leakage of the protein myoglobin into the blood or the urine, the latter of which usually becomes dark reddish brown or the color of cola. The disease, which can lead to acute renal failure and death, is diagnosed when the creatine kinase level is higher than 10,000 times the upper limit of normal regardless of any change in renal function, or when it is higher than 10 times the upper limit of normal in the presence of worsening renal function or a medical necessity for IV hydration therapy or both.

Rhabdomyolysis can occur with the use of any statin, but its incidence is quite rare and it is most likely to develop if the circulating drug level is high, as would be expected in the administration of a high daily dose. Because simvastatin, like other statin drugs, is metabolized through the cytochrome P (CYP)-450 isoenzyme pathway CYP3A4, concurrent administration of a drug that inhibits that isoenzyme decreases the metabolism of simvastatin, consequently increasing its circulating level. The drug amiodarone inhibits CYP3A4, and the risk of rhabdomyolysis seems to be greatest when the patient takes a high dose of simvastatin or a drug containing it concurrently with amiodarone. Therefore, the FDA recommends that patients taking both drugs should take no more than 20 mg of simvastatin daily; the maximum recommended daily dose is 80 mg. Nurses should check the daily simvastatin dosage if the patient is also taking amiodarone, and patients who complain of muscle pain or weakness or both should be evaluated for rhabdomyolysis--the creatine kinase level should be assessed and any change in the urine color should be noted. Consult the prescriber if there is any indication of the presence of the disease. The effects of using other statins concurrently with amiodarone are not known.

Aschenbrenner DS, Venable SJ. Drug therapy in nursing. 3rd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins; 2009; Center for Drug Evaluation and Research. Postmarketing reviews: interaction between amiodarone (marketed as Cordarone and Pacerone) and simvastatin (marketed as Zocor and generics) or simvastatin-combination products (marketed as Vytorin and Simcor). FDA Drug Safety Newsletter 2008;1(4). http://www.fda.gov/cder/dsn/2008_summer/postmarketing.htm#amiodarone_simvastatin; U.S. Food and Drug Administration. FDA analysis shows cholesterol lowering medications do not increase the risk of "Lou Gehrig's Disease": Agency recommends no change in prescribing and use of statins [press release]. FDA News 2008 Sept 29. http://www.fda.gov/bbs/topics/NEWS/2008/NEW01892.html.