General Information

Benznidazole is a nitroimidazole antimicrobial.

Benznidazole is specifically indicated for use in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis), caused by Trypanosoma cruzi.

Benznidazole is supplied as a tablet for oral administration. Benznidazole Tablets are dosed by body weight. The total daily dose for pediatrics 2 to 12 years of age is 5mg/kg to 8mg/kg orally administered in two divided doses separated by approximately 12 hours, for a duration of 60 days. Please see drug label for specific dosing based on weight.

Mechanism of Action

Benznidazole is a nitroimidazole antimicrobial. Benznidazole inhibits the synthesis of DNA, RNA, and proteins within the T. cruzi parasite. Studies suggest that benznidazole is reduced by a Type I nitroreductase (NTR) enzyme of T. cruzi producing a series of short-lived intermediates that may promote damage to several macromolecules including DNA. In mammalian cells, however, benznidazole is metabolized by reduction of the nitro group to an amino group by a Type II NTR enzyme. The precise mechanism of action is not known.

Clinical Trial Results

The FDA approval of benznidazole was based on two adequate and well-controlled trials (Trial 1 and Trial 2): Trial 1 was a randomized, double-blind, placebo-controlled trial in children 6 to 12 years of age with chronic indeterminate Chagas disease conducted in Argentina. The chronic indeterminate form of Chagas disease includes patients with serologic evidence of T. cruzi infection without symptoms of cardiac or gastrointestinal disease. A total of 106 patients were randomized to receive either benznidazole (5 mg/kg/day for 60 days) or placebo and followed for 4 years. Patients with at least two positive conventional serologic tests for antibodies to T. cruzi were included in the study. The conventional serologic tests used include indirect hemagglutination assay (IHA), immunofluorescence antibody assay (IFA), and/or enzyme linked immunosorbent assay (ELISA) and were based on the detection of antibodies against T. cruzi parasites. Trial 2 was a randomized, double-blind, placebo-controlled trial in pediatric patients 7 to 12 years of age with chronic indeterminate Chagas disease conducted in Brazil. A total of 129 patients were randomized to receive either benznidazole (7.5 mg/kg/day for 60 days) or placebo and followed for 3 years. Patients with three positive conventional serologic tests for antibodies to T. cruzi were included in the study. The conventional serologic tests include IHA, IFA, and/or ELISA and were based on the detection of antibodies against T. cruzi parasites. In the first trial, approximately 60% of children treated with benznidazole had an antibody test change from positive to negative compared with about 14% of who received a placebo. In the second trial approximately 55% of children treated with benznidazole had an antibody test change from positive to negative compared with 5% who received a placebo. An additional study of the safety and pharmacokinetics of benznidazole in children aged 2 to 12 years supports the dosing recommendations down to 2 years of age.