Tufan Abdurrahman, Dede Didem Sener, Cavus Safak, Altintas Neriman Defne, Iskit Alper Bektas, Topeli Arzu
Faculty of Medicine, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.
Ann Pharmacother. 2006 Jul-Aug;40(7-8):1466-9. doi: 10.1345/aph.1H064. Epub 2006 Jun 13.
To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment.
A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis.
Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities.
We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.
报告一例在接受常规秋水仙碱治疗的患者中服用阿托伐他汀后发生严重横纹肌溶解的病例。
一名患有肾病综合征和淀粉样变性的45岁男性出现呼吸困难、意识改变和严重疲劳。他因淀粉样变性服用秋水仙碱1.5毫克/天，持续3年，无不良反应。入院前一个月，因高胆固醇血症开始服用阿托伐他汀10毫克/天。阿托伐他汀治疗2周后，他开始出现肌痛和肌肉力量下降。入院时肌酐和肌酸激酶浓度分别为8.1毫克/分升和9035单位/升。患者被诊断为横纹肌溶解，伴有肌红蛋白尿性少尿性急性肾衰竭，肌酸激酶浓度升高超过50倍。停用阿托伐他汀和秋水仙碱后，他的肌肉力量有所改善。然而，他因住院期间发生的医院获得性肺炎死亡。Naranjo概率量表显示阿托伐他汀和秋水仙碱可能是横纹肌溶解的原因。
阿托伐他汀和秋水仙碱具有众所周知的肌毒性不良反应。尽管阿托伐他汀已被证明安全，但与某些药物（如秋水仙碱）联合使用时，它成为一种潜在的肌毒性药物。这可能是因为他汀类等P-糖蛋白底物与作为P-糖蛋白抑制剂的秋水仙碱联合给药，通过增加底物的生物利用度和器官摄取来改变药代动力学，导致更多不良反应和毒性。
我们建议在同时开具2种或更多潜在肌毒性药物后1周、肌毒性药物剂量增加后或向已使用其他肌毒性药物的患者开具新药后检查肌酸激酶水平。
