drug interaction

Case: A 62-year-old male with a past medical history of diabetes mellitus, hyperlipidemia, atrial fibrillation, hypertension, and mild renal insufficiency - presented to the ER with severe weakness, anuria, and renal failure. The patient reported extremely dark urine for a few days before presentation. The patient was discharged 5 weeks ago from the hospital with Aspirin, Coumadin, Lopressor, Amiodarone, and simvastatin. ED laboratory workup showed creatine kinase (CK) in the 80,000 U/L range. BUN 65 mg/dL, creatinine 4.6 mg/dL. Liver function tests (LFT) are also moderately elevated. Which drug interactions can be the reason for this life-threatening Rhabdomyolysis?

Answer: Simvastatin-Amiodarone Interaction

Simvastatin is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This drug interaction may cause severe, life-threatening Rhabdomyolysis. The risk is higher in patients, particularly with simvastatin doses greater than 20 mg daily.

#pharmacology

References:

1. Marot A, Morelle J, Chouinard VA, Jadoul M, Lambert M, Demoulin N. Concomitant use of simvastatin and amiodarone resulting in severe rhabdomyolysis: a case report and review of the literature. Acta Clin Belg. 2011 Mar-Apr;66(2):134-6. doi: 10.2143/ACB.66.2.20625533. PMID: 21630612.

2. Ricaurte B, Guirguis A, Taylor HC, Zabriskie D. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother. 2006 Apr;40(4):753-7. doi: 10.1345/aph.1G462. Epub 2006 Mar 14. PMID: 16537817.

3. Borders-Hemphill V. Concurrent use of statins and amiodarone. Consult Pharm. 2009 May;24(5):372-9. doi: 10.4140/tcp.n.2009.372. PMID: 19555146.