p; There have been reports of pregnant women with life-threatening symptoms associated with acute Chagas disease who were treated with benznidazole. If a pregnant women presents with acute symptomatic Chagas disease, the risks versus benefits of treatment with Benznidazole Tablets to the mother and the fetus should be eva luated on a case-by-case basis.
Data
Animal Data
In an embryo-fetal toxicity study in pregnant rats, an oral dose of benznidazole of 150 mg/kg/day during organogenesis (days 6-17 of gestation) was associated with maternal weight loss, reduced fetal weights, and smaller litter sizes. Benznidazole was also associated with a low incidence of fetal malformations including anasarca in one fetus at a dose of 50 mg/kg/day and anasarca and eye abnormalities (anophthalmia and microphthalmia) in 5 fetuses in 5 litters at a high dose of 150 mg/kg/day (approximately equivalent to 1 and 3 times, respectively, the MRHD based on whole body surface area comparisons). The No Observed Adverse Effect Level (NOAEL) dose for maternal toxicity in this study, 50 mg/kg/day, is approximately equal to the MRHD based on body surface area comparisons. The NOAEL dose for fetal toxicity was 15 mg/kg/day which is approximately equivalent to 0.3 times the MRHD based on whole body surface area comparisons.
In an embryo-fetal study in pregnant rabbits, oral (gavage) administration of benznidazole during organogenesis (days 6 to 19 of gestation) at a high dose of 25 mg/kg/day was associated with maternal toxicity including reduced weight gain and food consumption and abortions in 2/20 females. Benznidazole was also associated with a low incidence of fetal abnormalities including ventricular septal defect in 2 fetuses in 2 litters at a dose of 7.5 mg/kg/day and in 1 fetus at a dose of 25 mg/kg/day (approximately equivalent to 0.3 and 1 times respectively the MRHD based on whole body surface area comparisons). The NOAEL values for maternal and fetal toxicity in this study were 7.5 and 2.5 mg/kg/day respectively, which are respectively equivalent to approximately 0.3 and 0.1 times the MRHD based on body surface area comparisons.
In a pre- postnatal study in rats, first generation (F1) pups born to dams administered 15, 50, and 75 mg/kg/day benznidazole demonstrated normal pre-weaning behavior, physical and functional development, neurological findings, and reproductive parameters. However, cesarean section data for the pregnant first generation (F1) females in the high-dose group included significantly higher pre-implantation loss and significantly lower mean values for corpora lutea counts, number of implantations, and number of live embryos. Also small testes and/or epididymides were observed in 1/20 and 2/20 first generation males in the mid- and high-dose groups respectively, and two of the affected animals failed to mate or induce pregnancy. However, the mean values for mating performance, fertility index, testes weight, testes and epididymides sperm counts, and epididymal sperm motility and progression were not altered in any of the F1 males in benznidazole treatment groups. The number of live second generation (F2) fetuses born to F1 dams was reduced in the high-dose group. The NOAEL value was considered to be 50 mg/kg/day which is approximately equal to the MRHD based on body surface area comparisons.
8.2 Lactation
Risk Summary
Limited published literature based on breast milk sampling reports that benznidazole is present in human milk at infant doses of 5.5 to 17% of |
