Schmidt Ginelle A, Hoehns James D, Purcell Jessica L, Friedman Robert L, Elhawi Yasir
Department of Pharmacy, University of Iowa College of Pharmacy, Iowa City, IA, USA.
J Am Board Fam Med. 2007 Jul-Aug;20(4):411-6. doi: 10.3122/jabfm.2007.04.060187.
To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure.
A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered.
The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors.
Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.
报告一例辛伐他汀、胺碘酮和阿扎那韦严重相互作用导致横纹肌溶解和急性肾衰竭的病例。
一名72岁白人男性，患有人类免疫缺陷病毒、心房颤动、冠状动脉疾病和高脂血症，出现全身疼痛、疲劳和深橙色尿液3天。患者睡前服用80毫克辛伐他汀（27天前开始）；胺碘酮，剂量为每日400毫克，共7天，然后每日200毫克（19天前开始）；以及每日400毫克阿扎那韦（至少2年前开始）。实验室检查显示肌酸激酶66,680 U/L、血尿素氮93 mg/dL、肌酐4.6 mg/dL、天冬氨酸氨基转移酶1579 U/L和丙氨酸氨基转移酶738 U/L。辛伐他汀、胺碘酮和患者的人类免疫缺陷病毒药物均暂时停用，患者接受强制碱性利尿并开始透析。9天后，患者的肌酸激酶降至1695 U/L，肌酐为3.3 mg/dL。患者出院后继续门诊透析1个月，直至肾功能恢复。
同时使用抑制辛伐他汀代谢的药物会增加横纹肌溶解的风险。辛伐他汀由CYP3A4代谢。胺碘酮和阿扎那韦是公认的CYP3A4抑制剂。
他汀类药物的药代动力学差异是评估潜在药物相互作用风险的重要考虑因素。在需要同时使用他汀类药物和CYP3A4抑制剂的患者中，普伐他汀、氟伐他汀和瑞舒伐他汀发生药物相互作用的风险最低；阿托伐他汀风险中等，而辛伐他汀和洛伐他汀风险最高，服用CYP3A4抑制剂的患者应避免使用。
