International Health Service, Hospital Clinic Barcelona, Barcelona, Spain.
ISGlobal, Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain.
J Antimicrob Chemother. 2018 Apr 1;73(4):1060-1067. doi: 10.1093/jac/dkx516.
Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies.
Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®).
Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly.
We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration.
There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.
苯硝唑是治疗恰加斯病最有效的两种抗寄生虫药物之一。然而，关于其毒性特征的知识主要基于上市后观察性研究。
我们的研究结合了两项旨在评估 ELEA 实验室新生产的药物（Abarax®）安全性的前瞻性临床试验的数据。
在 2013 年至 2016 年期间，使用连续抽样策略从 CINEBENZ 和 BIOMARCHA 研究中选择合格的参与者（EUDRACT 2011-002900-34 和 2012-002645-38，分别和 clinicaltrials.gov NCT01755403 和 NCT01755377）。入组患者接受 5mg/kg/天苯硝唑口服，分两次给药，疗程 8 周，并每两周随访一次。
我们观察到 99 名参与者中的 85 名（85.9%）出现了 305 种不良反应。每位患者的不良反应中位数为 3 种，89.5%为轻度，中位持续时间为 12 天。大多数不良反应出现在治疗的第一个月，除关节炎和周围神经病外。26 名患者未完成治疗：2 名退出，1 名因异位妊娠，1 名因囊虫病导致癫痫复发；2 名失访；22 名因不良反应，其中 2 名严重。我们观察到一些以前未描述过的意外不良反应，如精神症状、勃起功能障碍、月经周期改变和肺浸润。
苯硝唑的不良反应发生率非常高。大多数不良反应为轻度，但治疗负担较大，且不常见的不良反应并不罕见。严重反应并不常见，但可能危及生命。需要进一步研究以优化治疗。
