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Simvastatin-Amiodarone Interaction Resulting in Rhabdomyolysis, Azotemia, and Possible Hepatotoxicity

Resident, Internal Medicine, Fairview Hospital and Cleveland Clinic Health System, Cleveland, OH

Amir Guirguis, MD

Assistant Program Director, Internal Medicine, Fairview Hospital and Cleveland Clinic Health System

Harris C Taylor, MD FACP FACE

Clinical Professor Medicine (Endocrinology), Division of Clinical and Molecular Endocrinology, School of Medicine, Case Western Reserve University, and Fairview Hospital and Cleveland Clinic Health System

Don Zabriskie, BSc MBA

Pharmacy Clinical Director for Medication Information, Fairview Hospital and Cleveland Clinic Health System

Reprints: Dr. Taylor, Fairview Hospital, 18101 Lorain Ave., Cleveland, OH 44111-9989, fax 216/476-2944, dkthct62{at}sbcglobal.net

OBJECTIVE: To describe the fifth reported instance, as of February 15, 2006, of a severe interaction between simvastatin and amiodarone and hypothesize inhibition of CYP3A4 as the major mechanism.

CASE SUMMARY: A 72-year-old white man (178 cm, 77.2 kg) with diabetes mellitus, hyperlipidemia, hypertension, and mild azotemia was hospitalized on September 21, 2004, with thigh weakness, achiness, and dark urine for 7 days. Coronary artery bypass had been performed on July 7, 2004. Amiodarone 200 mg/day was started on July 10, and simvastatin 80 mg/day was initiated on August 13. Laboratory testing on the present admission included creatine kinase (CK) 19 620 U/L (reference range 60-224), blood urea nitrogen 50 mg/dL, creatinine 2.6 mg/dL, aspartate aminotransferase (AST) 912 U/L (30-60), alanine aminotransferase (ALT) 748 U/L (30-60), urine myoglobin 71100 µg/L (<50), and serum myoglobin 13 877 µg/L (<110). Simvastatin and amiodarone were discontinued, and the patient was hydrated with forced alkaline diuresis. Thirteen days later, his CK was 323 U/L, creatinine 1.7 mg/dL, ALT 145 U/L, and AST 37 U/L.

DISCUSSION: Simvastatin is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This may, therefore, account for the presumed drug interaction.

CONCLUSIONS: An objective causal assessment suggests that rhabdomyolysis, renal failure, and possibly hepatotoxicity were probably related to an amiodarone-simvastatin interaction.

Key Words: rhabdomyolysis, simvastatin-amiodarone interaction

Published Online, March 14, 2006. www.theannals.com, DOI 10.1345/aph.1G462

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