替比夫定致患者横纹肌溶解不良反应的文献分析

Analysis on Literatures of Adverse Drug Reactions Induced by Tibioftin in Patients with Rhabdomyolysis

目的:分析替比夫定致患者横纹肌溶解不良反应的临床特点与预后及相关因素,为临床安全用药提供参考。方法:检索国内外公开发表的替比夫定致横纹肌溶解的案例,分析纳入患者的一般情况、用药情况、不良反应的发生时间及症状、实验室检查、肌活检和预后等资料。结果:纳入的13份案例中,涉及患者13例,所有患者均为男性,平均年龄为(29.8±9.9)岁;其发生不良反应的中位时间为11月,症状初始表现以双下肢无力、疼痛为主,常伴有恶心、呕吐;初始表现为反复恶心、呕吐的有3例患者,其中2例患者表现为双下肢肿胀;所有患者的肌酸激酶(CK)均明显升高,部分患者的血乳酸值(LA)也明显升高;经停药及其他对症处理后3例患者病死。结论:替比夫定致患者横纹肌溶解不良反应的潜伏期较长,单独使用或与其他抗病毒药物联用均可导致该不良反应的发生。CK值的监测可能具有预防横纹肌溶解发生的作用,但不可完全依赖;在诊治过程中注意监测LA,警惕合并乳酸酸中毒,线粒体的毒性可能是替比夫定致患者横纹肌溶解的病理机制之一。

Objective:To analyze the clinical characteristics, prognosis and related factors induced by tibioftin in patients with rhabdomyolysis, and to provide a reference for the clinical safety of drug usage. Methods:Reports of telbivudine associated rhabdomyolysis were retrieved in domestic and foreign medical literature databases. The general information, medication, occurrence time and symptoms of adverse reactions, results of laboratory examination and muscle biopsy, and prognosis were collected and analyzed. Results:A total of 13 articles entered this investigation and involving 13 patients. The sexes of all patients were male. The average age of them was 29.77±9.91, and the median time of adverse reactions’ latent period was 11 months. The initial manifestations of most patients were myalgia and muscle weakness of lower limbs, often accompanied by nausea and vomiting. Three patients’ initial manifestations were recurrent nausea and vomiting, and two patients’ were swelling of lower limbs. The CK values of all patients were significantly increased, and LA values in some patients increased significantly also. The therapeutic measures were stopping telbivudine and providing symptomatic treatment, and 3 patients died finally. Conclusion:The latent period of telbivudine associated rhabdomyolysis is comparatively long, and this adverse reaction can be induced by telbivudine alone or combines with other antiviral drugs. Monitoring CK values might be an effective precautionary measure, but with low reliability. LA values should be monitored during the treatment of rhabdomyolysis, and be vigilant against lactic acidosis. Mitochondrial toxicity might be one of the pathological mechanisms of telbivudine induced rhabdomyolysis.