Case: 58 years old male is admitted to the ICU with Atrial fibrillation with RVR (rapid ventricular rate). The patient did well with rate control therapy and has been discharged from the hospital on metoprolol, aspirin, lisinopril, simvastatin, and Amiodarone. The patient presented back after 2 weeks to the ED with complaints of severe generalized weakness. The patient was found to be in acute renal failure. Besides hyperkalemia and elevated creatinine, the patient was found to have CPK in the 60,000 range. Troponin is normal. Which two drug interactions may be a culprit?
Answer: Simvastatin with amiodarone.
Simvastatin with amiodarone interaction may cause rhabdomyolysis and lead to acute renal failure. The FDA has already put out a warning regarding this drug interaction. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone.
The precise mechanism is not clearly known, but amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme, which is also the enzyme that metabolizes simvastatin.
Using other statins without relevant CYP metabolism (e.g., pravastatin) should be okay.
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Reference:
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. Roten L, Schoenenberger RA, Krähenbühl S, Schlienger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother. 2004 Jun;38(6):978-81. doi: 10.1345/aph.1D498. Epub 2004 Apr 6. PMID: 15069169.
3. Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, Funck-Brentano C. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther. 2007 May;81(5):679-84. doi: 10.1038/sj.clpt.6100098. Epub 2007 Feb 14. PMID: 17301736.
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