Benznidazole

Indications

Benznidazole is used for: Chagas disease (American trypanosomiasis)

Adult Dose

Child Dose

Chagas Disease Indicated in children aged 2-12 years for treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi <2 years: Safety and efficacy not established 2-12 years: 5-8 mg/kg/day PO divided in 2 doses separated by ~12 hr x 60 days Recommended weight-based doses <15 kg: 50 mg PO q12hr 15 kg to <20 kg: 62.5 mg PO q12hr 20 kg to <30 kg: 75 mg PO q12hr 30 kg to <40 kg: 100 mg PO q12hr 40 kg to <60 kg: 150 mg PO q12hr >60 kg: 100 mg PO q12hr

Renal Dose

Administration

Dosage based on body weight; 100-mg tablets are scored and can be split in half (50 mg) or quarters (25 mg) to enable precise dosing

Contra Indications

Patients who have taken disulfiram within the last 2 weeks; psychotic reactions may occur Consumption of alcoholic beverages or products containing propylene glycol during and for at least 3 days after the last dose; disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) may occur owing to the interaction between alcohol or propylene glycol and benznidazole History of hypersensitivity reaction to benznidazole or other nitroimidazole derivatives; severe skin and soft tissue reactions reported

Precautions

Genotoxicity of benznidazole has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodent Carcinogenicity observed in mice and rats treated chronically with nitroimidazole agents which are structurally similar to benznidazole Embryofetal toxicity may occur

Pregnancy-Lactation

Pregnancy Based on findings from animal studies, can cause fetal harm when administered to pregnant women Obtain pregnancy test in females of reproductive potential before initiating treatment Animal studies Benznidazole administered PO to pregnant rats and rabbits during organogenesis was associated with fetal malformations at doses ~1-3 times the maximum recommended human dose (MRHD) in rats (anasarca, anophthalmia, and/or microphthalmia) and doses ~0.3-1 times the MRHD in rabbits (ventricular septal defect) Contraception Advise females of reproductive potential to use effective contraception during treatment and for 5 days after the final dose Fertility Based on findings in rodents, may impair fertility in males of reproductive potential Unknown whether effects on fertility are reversible Lactation Present in human milk at infant doses of 5.5-17% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.3­2.79 Because of the potential for serious adverse reactions and transmission of Chagas disease, advise patients that breastfeeding is not recommended during treatment

Interactions

Psychotic reactions reported with coadministration of disulfiram and nitroimidazole agents (structurally related to benznidazole); do not coadminister or use in patients who have taken disulfiram within the last 2 weeks

Adverse Effects

Side effects of Benznidazole : >10% Abdominal pain (25%) Rash or skin lesions (11-16%) Weight decreased (13%) 1-10% Nausea (5%) Vomiting (5%) Increased AST/ALT (5%) Diarrhea (4%) Dizziness (4%) Peripheral neuropathy (2%) Tremor (2%)

Mechanism of Action

Nitroimidazole antimicrobial; generates radical species in both aerobic and anaerobic conditions that are capable of damaging parasitic DNA Inhibits DNA, RNA, and protein synthesis within the T cruzi parasite Studies suggest 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