Tuesday, August 12, 2008

Tuesday August 12, 2008

Case: 58 year old male is admitted to ICU with Atrial fibrillation with RVR (rapid ventricular rate). Patient did well with rate control therapy and has been discharged from hospital on metoprolol, aspirin, lisinopril, simvastatin and Amiodarone. Patient presented back after 2 weeks to ED with complain of severe generalized weakness. Patient was found to be in acute renal failure. Beside hyperkalemia and elevated creatinine, patient found to have CPK in 60,000 range. Troponin is normal. Your diagnosis ?



Answer: Acute renal failure secondary to rhabdomyolysis caused by simultaneous use of simvastatin with amiodarone.

Though it has been reported in literature earlier, FDA recently issued warning regarding above drug interaction 1. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone.

Precise mechanism is not clearly known, but amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme. This is the same enzyme that metabolizes simvastatin
2.

Use of other statins without relevant CYP metabolism (eg, pravastatin) should be ok.


Reference: click to get abstract

1. Simvastatin (marketed as Zocor and generics), Ezetimibe/Simvastatin (marketed as Vytorin), Niacin extended-release /Simvastatin (marketed as Simcor), used with Amiodarone (Cordarone, Pacerone) - fda.gov

2.
Rhabdomyolysis in Association with Simvastatin and Amiodarone - The Annals of Pharmacotherapy: Vol. 38, No. 6, pp. 978-981.

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