【摘要】 目的系统评价左氧氟沙星全身给药对儿童骨关节不良事件的发生情况。方法计算机检索Pub Med、Cochrane图书馆、OVID、EBSCO、中国知网、中国维普科技期刊数据库和万方数据库,检索时间从1993年1月至2015年1月;同时手工检索中国《药品不良事件信息通报》、WHO Pharmaceuticals Newsletter和FDA Drug Safety Newsletter;还检索美国、中国和欧盟药品监督和管理部门的网站;获得儿童使用左氧氟沙星全身给药的不良事件资料。按照纳入和排除标准筛选文献。对纳入的RCT文献行偏倚风险评价。结果行描述性分析。结果检索获得286篇文献,11篇文献进入系统评价,包括RCT 5篇、病例系列/报告6篇和上市后药物不良事件监测2篇。美国FDA网站检索到25份关于儿童使用左氧氟沙星出现不良事件的报告。1RCT文献:2篇文献结果显示左氧氟沙星组与对照组骨关节不良事件发生率差异无统计学意义,3篇文献未报告骨关节不良事件;2病例系列/报告:3篇涉及左氧氟沙星骨关节不良事件,分别报告14例轻微的骨关节疼痛(14/26),跛行和踝关节痛各1例(2/204),掌指关节炎和踝关节痛各1例(2/5),骨关节炎症状均在停药或疗程结束后消失。3上市后药物不良事件监测:2篇文献(1项研究,n=2 233)报告左氧氟沙星骨关节损害(关节痛、关节炎、跟腱炎和步态异常)发生率在1.7%~3.4%,1年内骨关节损害发生率高于对照组,在2~5年随访时骨关节损害发生率与对照组相近;4美国FDA不良事件报告:8份报告的主要症状呈现为骨关节不良事件,其中6篇报告因信息不完整致因果关系无法评价,2篇评价为可能;5美国和中国FDA均批准>6月龄儿童吸入性炭疽(暴露后)使用左氧氟沙星;欧盟药品管理局批准了6项儿童使用左氧氟沙星治疗囊性纤维化的试验。结论现有证据显示,儿童应用左氧氟沙星骨关节不良事件的发生率较低,且多数在随访中可以缓解;作为充分评估风险和利益后左氧氟沙星超说明书使用时提供参考。更多还原

【Abstract】 Objective To evaluate musculoskeletal adverse drug events( ADEs) of levaquin in children. Methods Clinical studies involving levaquin used in children were identified from Pub Med,Cochrane Library,OVID,EBSCO,CNKI,VIP and Wanfang Database. Other resources were searched manually,including State Food and Drug Adminstration( SFDA),Drug Adverse Event Report,WHO Pharmaceuticals Newsletter and FDA Drug safety Newsletter,and search time was from 1993 to 2015. Data were extracted and evaluated according to the inclusion and exclusion criteria and then the quality of included randomized clinical trials( RCTs) was evaluated. Results A total of 286 studies were found and 11 studies were finally included in the systematic review,including 5 RCTs,6 case series and 2 postmarketing surveillance reports. Quality of 2 of the 5 RCTs was good,and the others were low. Twenty-five reports applying levaquin in children were found in FDA website. Two RCTs showed in levaquin group and control group musculoskeletal ADEs rate was not statistically significant,but others were not,owing to the limitation of low sample size and simple record in follow-up. Three case serieses reported musculoskeletal ADEs,14 with slight bone pain( 14 /26),1claudication,1 ankle pain( 2 /204),1 metacarpophalangeal polyarthritis and 1 ankle arthralgia( 2 /5). The symptoms disappeared after stopping the drug or off the therapy. Two postmarketing surveillance( 1 study,n = 2 233) reports showed musculoskeletal disorder rate of levaquin ranged from 1. 7% to 3. 4%. After 1 year,musculoskeletal disorder rate of levaquin group was higer than that of control group,but in 2 to 5 years follow-up of two groups it became similar. The main symptoms of the 8 reports were musculoskeletal ADEs. Because of the incomplete information,6 reports could not be evaluated,and 2 reports evaluation was possible. Both FDA and CFDA approved children( >6 months) with inhalation anthrax( exposed) using levaquin. EMA allowed to use levofloxacin for the treatments of cystic fibrosis. Conclusion The present profile shows the low musculoskeletal ADEs rate of levaquin and most relief in the follow-up in children to provide the evidence of levaquin off label use after comprehensive risk and benefit assessment.更多还原