European Journal of Internal Medicine 17 (2006) 148 www.elsevier.

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Letter to the Editor

Myopathy from the combination of simvastatin and amiodarone

W.R. Saliba *, M. Elias
Department of Internal Medicine C, HaemeK Medical Center, Afula 18101, Affiliated to the Technion-Israel Institute of Technology, Faculty of Medicine, Haifa, Israel Received 16 September 2005; accepted 26 September 2005

Keywords: Myopathy; Simvastatin; Statin; Amiodarone

Treatment with statins has been associated with myopathy ranging from myalgia to severe, life-threatening rhabdomyolysis [1]. Only a minority of patients develop myopathy in response to lipid-lowering agents [1]. The incidence of myopathy is probably similar for all lipid-lowering agents, in the range of 0.1 0.5%. This risk is increased in patients who receive other drugs that may interfere with statin metabolism. The co-administration of amiodarone with simvastatin has seldom been associated with myopathy [2]. We present a patient who developed myopathy from the co-administration of amiodarone and simvastatin. A 74-year-old woman presented complaining of dizziness. Her past medical history was remarkable for type 2 diabetes mellitus with end-organ damage including nephropathy and retinopathy. In addition, she had hypertrophic nonobstructive cardiomyopathy and diastolic congestive heart failure. Her medications included aspirin, simvastatin, carvidolol, insulin, and furosemide. An electrocardiogram revealed a rapid, newly diagnosed atrial fibrillation that converted spontaneously to a normal sinus rhythm. Upon restoration of the normal cardiac rhythm, her symptoms improved dramatically. The patient was placed on warfarin and amiodarone for rhythm control. Six days later, she presented with complaints of effort dyspnea without chest pain. An electrocardiogram showed sinus bradycardia, 50 bpm, without ischemic changes. Laboratory tests showed white blood cells 6330/ mm3, hemoglobin 10.7 g/dL, platelets 183 000/mm3, urea 145 mg/dL, creatinine 2.5 mg/dL, creatine phosphokinase (CPK) 730 IU/L, lactate dehydrogenase (LDH) 1400 IU/L,
* Corresponding author. Tel.: +972 4 6495139; fax: +972 4 6495127. E-mail address: salibuss@yahoo.com (W.R. Saliba).

alanine aminotransferase 137 IU/L, aspartate aminotransferase 112 IU/L, and alkaline phosphatase 151 IU/L. The CPKMB fraction and troponin T levels were not increased. The patient denied strenuous exercise, recent trauma, or intramuscular drug injection. The elevated LDH and the CPK levels with a normal CPK-MB fraction and troponin without evidence of ischemia on electrocardiogram, in addition to the concomitant elevation in transaminases, argue against ischemia as a cause for the elevation of these enzymes. On the other hand, the elevated level of these enzymes 6 days after treatment with amiodarone strongly suggests amiodarone as the cause of these abnormalities. HMG-CoA reductase inhibitors are primarily metabolized by the cytochrome P450, isoenzyme CYP3A4 [1]. By inhibiting CYP3A4, amiodarone increases the plasma concentration of simvastatin and significantly increases the risk of myopathy [2]. The co-administration of statins and amiodarone is frequent in patients with heart disease. Doctors should be aware of the risk of myopathy when combining the two. For patients who need to be treated with a combination of statins and amiodarone, we recommend either reducing the statin dosage or using another statin that is not metabolized by the CYP3A4.

References
[1] Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003;289:1681 90. [2] Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother 2004;38:978 81.

0953-6205/$ - see front matter D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2005.09.018