Benznidazole

Benznidazole has a significant activity during the acute phase of Chagas disease, with a success rate of up to 80%. Its curative capabilities during the chronic phase are, however, limited. Some studies have found parasitologic cure (a complete elimination of T. cruzi from the body) in children during the early stage of the chronic phase, but overall failure rate in chronically infected individuals is typically above 80%. A formulation for children up to two years of age is available. It was added to the WHO Essential Medicines List for Children in 2013. Children are found to be at a lower risk of adverse events compared to adults, possibly due to increased hepatic clearance of the drug. The most prevalent adverse effects in children were found to be gastrointestinal, dermatologic, and neurologic in nature. However, the incidence of severe dermatologic and neurologic adverse events is lower in the pediatric population compared to adults. It use for Chagas in children was approved by the FDA in the US in 2017. Pregnant women Studies in animals have shown that benznidazole can cross the placenta. Due to its potential for teratogenicity, use of benznidazole in pregnancy is not recommended. ==Side effects==

Side effects tend to be common and occur more frequently with increased age. Benznidazole may cause photosensitization of the skin, resulting in rashes. Rashes usually appear within the first 2 weeks of treatment and resolve over time. In rare instances, skin hypersensitivity can result in exfoliative skin eruptions, edema, and fever. Peripheral neuropathy may occur later on in the treatment course and is dose dependent. It is not permanent, but takes time to resolve. Other adverse reactions include anorexia, weight loss, nausea, vomiting, insomnia, and dysgeusia, and bone marrow suppression. Gastrointestinal symptoms usually occur during the initial stages of treatment and resolves over time. Bone marrow suppression has been linked to the cumulative dose exposure. == Contraindications ==

Benznidazole should not be used in people with severe liver and/or kidney disease. == Pharmacology ==

Mechanism of action Benznidazole is a nitroimidazole antiparasitic with good activity against acute infection with Trypanosoma cruzi, commonly referred to as Chagas disease. The mechanism by which nitroimidazoles do this seems to depend on whether or not oxygen is present. This is particularly relevant in the case of Trypanosoma species, which are considered facultative anaerobes. Under anaerobic conditions, the nitro group of nitroimidazoles is believed to be reduced by the pyruvate:ferredoxin oxidoreductase complex to create a reactive nitro radical species. 5% of the parent drug is excreted unchanged in the urine, which implies that clearance of benznidazole is mainly through metabolism by the liver. Its elimination half-life is 10.5-13.6 hours. == Interactions ==

Benznidazole and other nitroimidazoles have been shown to decrease the rate of clearance of 5-fluorouracil (including 5-fluorouracil produced from its prodrugs capecitabine, doxifluridine, and tegafur). While co-administration of any of these drugs with benznidazole is not contraindicated, monitoring for 5-fluorouracil toxicity is recommended in the event they are used together. The GLP-1 receptor agonist lixisenatide may slow down the absorption and activity of benznidazole, presumably due to delayed gastric emptying. Because nitroimidazoles can kill Vibrio cholerae cells, use is not recommended within 14 days of receiving a live cholera vaccine. Alcohol consumption can cause a disulfiram like reaction with benznidazole. == References ==