近日，美国食品和药物管理局（FDA）批准benznidazole（苯并乙唑，也叫苯硝唑）用于患有Chagas病的2至12岁儿童。这是美国批准用于治疗查加斯病（也叫恰加斯病，Chagas disease）的首例治疗方法。
FDA药物评估和研究中心的抗菌药物办公室主任爱德华·考克斯（Edward Cox）说：“FDA致力于提供安全有效的治疗热带疾病的治疗方案。
批准日期：2017年8月30日 公司：Exeltis USA, Inc
BENZNIDAZOLE（苯硝唑 Benznidazole）片剂，用于口服
美国最初批准：2017年
作用机制
苯并咪唑是硝基咪唑抗微生物药[见微生物学]。
适应症和用法
苯并咪唑片剂，一种硝基咪唑抗菌剂，适用于2至12岁的儿科患者，用于治疗由克氏锥虫引起的南美锥虫病（美洲锥虫病）。
该指征在加速批准的基础上批准，其基于治疗的患者的数量，其成为针对克氏锥虫的重组抗原阴性的免疫球蛋白G（IgG）抗体。对该指征的持续批准可能取决于确认试验中的临床益处的验证和描述。
剂量和给药
•2至12岁的儿科患者：总日剂量为5mg/kg至8mg/kg，以两个分开的剂量口服给药，间隔约12小时，持续60天。
•有关重要的管理说明，请参阅完整的处方信息。
剂量形式和强度
•片剂：100毫克（功能评分）。
•片剂：12.5mg。
禁忌症
•对苯并咪唑或其他硝基咪唑衍生物的超敏反应史。
•过去两周内使用双硫仑。
•治疗期间和治疗期间至少三天饮用酒精饮料。
警告和注意事项
•遗传毒性和致癌性的潜在风险。
•胚胎-胎儿毒性：可能导致胎儿伤害。建议对有生育潜力的女性进行妊娠试验。告知女性有可能对胎儿造成潜在风险的生殖潜力，并使用有效的避孕措施。
•苯并咪唑引起过敏性皮肤反应。如果出现皮肤反应，出现全身受累的其他症状，如淋巴结肿大，发热和/或紫癜，建议停止治疗。
•苯并咪唑片治疗可能引起感觉异常或周围神经病变症状。在出现神经症状的情况下，建议立即停止治疗。
•有骨髓抑制的血液学表现，如中性粒细胞减少，血小板减少，贫血和白细胞减少。
不良反应
观察到的最常见的不良反应是腹痛，皮疹，体重减轻，头痛，恶心，呕吐，中性粒细胞减少，荨麻疹，瘙痒，嗜酸性粒细胞增多，食欲减退。
要报告疑似不良反应，请致电1-877-324-9349联系Exeltis USA，Inc。或致电1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系FDA。
用于特定人群
哺乳期：不推荐母乳喂养
包装提供/存储和处理
提供
苯并咪唑片（12.5mg或100mg）如下：
•100毫克白色片剂，圆形和功能性两侧十字交叉评分。 每个片剂的直径约10mm，在每个四分之一部分的一侧上用“E”进行压印。
•12.5毫克白色片剂，圆形和未刻痕。 每片直径约5mm，在一侧用“E”压印。
苯并咪唑片100mg可以100片（NDC 0642-7464-10）的瓶装。
苯并咪唑片12.5mg可以100片（NDC 0642-7463-12）的瓶装获得。
存储和处理
储存在20°C至25°C（68°F至77°F）的受控室温下; 允许偏移15°C至30°C（59°F至86°F）[见USP受控室温]。 保持瓶子紧闭，防止受潮。
完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8983d6a0-f63f-4f8e-bba4-38223f39e29b

Benznidazole(Benznidazole Tablets, for Oral Use)
INDICATIONS AND USAGE
Benznidazole Tablets, a nitroimidazole antimicrobial, is indicated in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi.
This indication is approved under accelerated approval based on the number of treated patients who became Immunoglobulin G (IgG) antibody negative against the recombinant antigens of T cruzi. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
Contraindications
Benznidazole Tablets are contraindicated in patients with a history of hypersensitivity reactions to benznidazole or other nitroimidazole derivatives. Reactions have included severe skin and soft tissue reactions. Benznidazole Tablets is also contraindicated in patients who have taken disulfiram within the last two weeks. Psychotic reactions may occur in patients who are using benznidazole and disulfiram concurrently. Consumption of alcoholic beverages or products containing propylene glycol is contraindicated in patients during and for at least 3 days after therapy with Benznidazole Tablets. A disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) may occur due to the interaction between alcohol or propylene glycol and benznidazole.
Warnings and Precautions
Potential for Genotoxicity and Carcinogenicity: Genotoxicity has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodents. A study evaluating the cytogenetic effect of benznidazole in pediatric patients ranging from 11 months to 11 years of age (the safety and effectiveness of Benznidazole Tablets in patients less than 2 years old has not been established) with Chagas disease demonstrated a two-fold increase in chromosomal aberrations. In pediatric patients with Chagas disease who were treated with benznidazole, the median incidence of micronucleated interphase lymphocytes in 20 patients increased two-fold compared to pre-dose values. In the same study, the mean incidence of chromosomal aberrations in 10 patients also increased two-fold compared to pre-dose values.
Carcinogenicity has been observed in mice and rats treated chronically with nitroimidazole agents, which are structurally similar to benznidazole. Similar data have not been reported for benznidazole. It is not known whether benznidazole is associated with carcinogenicity in humans.
Embryo-Fetal Toxicity: Based on animal studies, Benznidazole Tablets can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for women of reproductive potential prior to Benznidazole Tablets therapy. Advise women of reproductive potential to use effective contraception during treatment with Benznidazole Tablets and for 5 days after the last dose.
Hypersensitivity Skin Reactions: Serious skin and subcutaneous disorders, including acute generalized exanthematous pustulosis (AGEP), toxic epidermal necrolysis (TEN), erythema multiforme, and eosinophilic drug reactions, have been reported with benznidazole. Discontinue treatment at first evidence of these serious cutaneous reactions. Extensive skin reactions, such as rashes, have also been reported. Most cases occurred after approximately 10 days of treatment with benznidazole. Most rashes resolved with treatment discontinuation. In case of skin reactions presenting with additional symptoms or signs of systemic involvement, such as lymphadenopathy, fever, and/or purpura, discontinuation of treatment is recommended.
Central and Peripheral Nervous System Effects: Benznidazole Tablets can cause paresthesia or symptoms of peripheral neuropathy that may take several months to resolve. Headache and dizziness have been reported. In cases where neurological symptoms occur, immediate discontinuation of treatment is recommended. In most cases, symptoms occur late in the course of treatment.
Hematological Manifestations of Bone Marrow Depression: There have been reports of hematological manifestations of bone marrow depression, such as neutropenia, thrombocytopenia, anemia, and leukopenia, which resolved after treatment discontinuation. Patients with hematological manifestations of bone marrow depression must take Benznidazole Tablets only under strict medical supervision. Monitor complete blood count. Total and differential leukocyte counts are recommended before, during, and after therapy.
Adverse Reactions
The most common adverse reactions observed were abdominal pain (25%), rash (16%), decreased weight (13%), and headache (7%).
Use in Specific Populations
Lactation Risk: Limited published literature based on breast milk sampling reports that benznidazole is present in human milk. There are no reports of adverse effects on the breastfed infant and no information on the effects of benznidazole on milk production. Because of the potential for serious adverse reactions, and transmission of Chagas disease, advise patients that breastfeeding is not recommended during treatment with Benznidazole Tablets.
Male Infertility: Based on findings in rodents, Benznidazole Tablets may impair fertility in males of reproductive potential. It is not known whether effects on fertility are reversible.