长期使用氯喹/羟氯喹不良反应/事件病例分析与药物相互作用

目的检索与分析长期应用氯喹/羟氯喹(CQ/HCQ)可能导致的药品不良反应/事件(ADR/AE)及相关影响因素,总结常见药物相互作用,为临床合理用药提供参考。方法通过检索PubMed、中国期刊全文数据库(CNKI)、万方数据库从建库至今CQ/HCQ引起的药物不良反应/事件的个案报道文献,设定服药3个月以上出现的ADR/AE为长期应用导致的ADR/AE,总结与CQ/HCQ可能产生严重相互作用的药物。结果共检索到文献1280篇,最终纳入85篇,其中视觉损伤51篇,出现黄斑病变35例,视力下降15例,视网膜病变1例,色盲1例,失明2例,停药后好转15例,未恢复38例,长期用药>5年、累积剂量超过1000 g的视觉损伤多不可恢复。心脏ADR/AE共24篇,病例31例,ADR/AE包括传导阻滞25例,心肌损伤17例,心衰15例;其中死亡4例,植入起搏器6例,心脏移植4例。皮肤ADR/AE纳入5篇,其他ADR/AE纳入5篇,主要表现为听力减退。结论临床长期使用CQ/HCQ可出现严重ADR/AE,包括心脏毒性、黄斑变性、听力减退等需注意监测;CQ/HCQ主要经CYP450酶代谢,使用过程中应注意药物相互作用的影响。

Common Adverse Drug Events due to Long-term Medication with Chloroquine/Hydroxychloroquine and Drug Interactions

Objective To investigate the possible adverse drug reactions caused by long-term use of chloroquine/hydroxychloroquine(CQ/HCQ)and related risk factors in order to provide evidence for rational clinical applications of these drugs.Methods Electronic databases including PubMed,CNKI and Wanfang were searched for possible ADR/AE caused by CQ/HCQ administration.ADR/AE that occurred more than 3 months after medication were identified as long-term ADR/AE.Results A total of 1280 articles were retrieved,85 of which were adopted.Among the 85 articles,51 involved visual impairment,including 35 cases of maculopathy,15 cases of vision decline,1 case of retinopathy,1 case of color blindness,and 2 cases of blindness.There were 15 cases of improvement after drug withdrawal,but 38 patients didn’t recover.Most of the cases of visual impairment could not recover with a cumulative dose>1000 g and after more than 5 years of medication.There were also 24 articles on heart related ADR/AE involving 31 patients.These ADR/AE involved 25 cases of conduction block,17 cases of myocardial injury and 15 cases of heart failure.There were 4 cases of death,6 cases of implantation with pacemakers and 4 cases of heart transplantation.There were 5 articles related to skin ADR/AE and another 5 ones related to other ADR/AE.Conclusion CQ/HCQ can cause serious ADR/AE,including cardiotoxicity,maculopathy,and hypoacusis.CQ/HCQ is mainly metabolized by CYP450 enzyme,so drug interactions deserve attention.