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. The nitro radical can then either engage in other redox reactions directly or spontaneously give rise to a nitrite ion and imidazole radical instead. The initial reduction takes place because nitroimidazoles are better electron acceptors for ferredoxin than the natural substrates. In mammals, the principal mediators of electron transport are NAD+/NADH and NADP+/NADPH, which have a more positive reduction potential and so will not reduce nitroimidazoles to the radical form. This limits the spectrum of activity of nitroimidazoles so that host cells and DNA are not also damaged. This mechanism has been well-established for 5-nitroimidazoles such as metronidazole, but it is unclear if the same mechanism can be expanded to 2-nitroimidazoles (including benznidazole).In the presence of oxygen, by contrast, any radical nitro compounds produced will be rapidly oxidized by molecular oxygen, yielding the original nitroimidazole compound and a superoxide anion in a process known as "futile cycling". In these cases, the generation of superoxide is believed to give rise to other reactive oxygen species. The degree of toxicity or mutagenicity produced by these oxygen radicals depends on cells ability to detoxify superoxide radicals and other reactive oxygen species. In mammals, these radicals can be converted safely to hydrogen peroxide, meaning benznidazole has very limited direct toxicity to human cells.
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%.Some studies indicate treatment with benznidazole during the chronic phase, even if incapable of producing parasitologic cure because it reduces electrocardiographic changes and delays worsening of the clinical condition of the patient.Benznidazole has proven to be effective in the treatment of reactivated  T. cruzi  infections caused by immunosuppression, such as in people with AIDS or in those under immunosuppressive therapy related to organ transplants. Children
Benznidazole can be used in children, with the same 5–7 mg/kg per day weight-based dosing regimen that is used to treat adult infections. 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.