Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity

The Annals of Pharmacotherapy
Basma RicaurteDon Zabriskie

Abstract

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. 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 71,100 microg/L (<50), and serum myoglobin 13,877 microg/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. Simvastatin is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This may, therefore, account for the presum...Continue Reading

References

Aug 1, 1981·Clinical Pharmacology and Therapeutics·C A NaranjoD J Greenblatt
Dec 5, 1998·The New England Journal of Medicine·UNKNOWN Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
Jan 5, 2000·Journal of Internal Medicine·A MogyorósiM L Schubert
Mar 7, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·M KatohT Yokoi
Sep 28, 2001·The Annals of Pharmacotherapy·M A OmarT S Cox
Dec 26, 2001·Clinical Pharmacology and Therapeutics·A B MulderI Vermes
Feb 15, 2002·The New England Journal of Medicine·Judy A StaffaLanh Green
Mar 11, 2003·Endocrine Journal·Maria José BarahonaAna María Wägner
Apr 19, 2003·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Pamela Wratchford, Charles D Ponte
Apr 24, 2003·Clinical Cardiology·Antonio M Gotto
Sep 16, 2003·The American Journal of Cardiology·Connie B NewmanMichael Szarek
Sep 16, 2003·The American Journal of Cardiology·David Waters
Apr 8, 2004·The Annals of Pharmacotherapy·Laurent RotenRaymond G Schlienger
Jul 31, 2004·Pharmacogenetics·Kari T KivistöTimo Strandberg
Jan 22, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rahul A NathwaniNeil Kaplowitz
Apr 15, 2005·Medical Reference Services Quarterly·Marie K Saimbert
Apr 30, 2005·Preventive Cardiology·Alawi A Alsheikh-Ali, Richard H Karas
Sep 15, 2005·The Annals of Pharmacotherapy·Uttamlal M ChouhanLaura J Millward
Jun 1, 2002·Journal of Clinical Neuromuscular Disease·Penelope A McKelvie, Xenia Dennett

❮ Previous
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Citations

Feb 21, 2008·Redox Report : Communications in Free Radical Research·Ashutosh LalBruce N Ames
Jun 27, 2009·The Consultant Pharmacist : the Journal of the American Society of Consultant Pharmacists·Vicky Borders-Hemphill
Jan 23, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Beatrice A Golomb, Marcella A Evans
Sep 19, 2009·Pharmacogenomics·Raúl J AndradeM Isabel Lucena
Jun 4, 2010·Clinical Chemistry and Laboratory Medicine : CCLM·Paola BrancaccioNicola Maffulli
Aug 16, 2006·Expert Opinion on Drug Safety·Atul TiwariKasim Mookhtiar
Aug 24, 2007·Expert Opinion on Pharmacotherapy·Jennifer G Robinson
Dec 24, 2009·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Kathy E SietsemaRoger G Ulrich
Apr 17, 2010·Gastroenterology·Naga Chalasani, Einar Björnsson
Sep 2, 2008·The Journal of Emergency Medicine·Alp ArkunRobert H Birkhahn
Jan 22, 2008·Clinics in Sports Medicine·Paola BrancaccioFrancesco Mario Limongelli
Aug 29, 2007·Clinics in Liver Disease·Sidharth S Bhardwaj, Naga Chalasani
Dec 30, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Giuliana PomponioEmanuela Testai
Mar 27, 2007·Pharmacotherapy·Espen Molden, Kirsti Svendsen Andersson
Jun 24, 2009·Orvosi hetilap·György Paragh, Péter Fülöp
Oct 6, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Susanna VichiEmanuela Testai
Sep 4, 2012·The American Journal of Medicine·Alicia LeungNeil J Stone
May 3, 2014·SpringerPlus·Maria Zhelyazkova-SavovaVera Sirakova
Oct 25, 2013·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Anida Causevic-Ramosevac, Sabina Semiz
Apr 25, 2017·Critical Reviews in Toxicology·Ana Margarida AraújoPaula Guedes de Pinho
Nov 19, 2009·The Annals of Pharmacotherapy·James M BackesPatrick M Moriarty
Feb 16, 2007·Clinical Pharmacology and Therapeutics·L BecquemontC Funck-Brentano
Oct 19, 2016·Circulation·Barbara S WigginsUNKNOWN American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology; Council on Hypertension; C
Apr 7, 2007·Current Opinion in Gastroenterology·Cherinne Arundel, James H Lewis
Jun 19, 2008·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Espen MoldenPia Braathen
Aug 29, 2007·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Tonja Merz, Stephen H Fuller
Nov 22, 2016·Lipid Insights·Jonathan T DaviesHollie I Swanson
Oct 23, 2018·SAGE Open Medicine·Ming-Ming YanMing-Kang Zhong
Aug 9, 2020·The Annals of Pharmacotherapy·Emily Cowley, Mohamed A Omar

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