the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.3-2.79. There are no reports of adverse effects on the breastfed infant and no information on the effects of benznidazole on milk production. Because of the potential for serious adverse reactions, and transmission of Chagas disease, advise patients that breastfeeding is not recommended during treatment with Benznidazole Tablets.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential.
Contraception
Females
Benznidazole Tablets can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Benznidazole Tablets and for 5 days after the final dose.
Infertility
Males
Based on findings in rodents, Benznidazole Tablets may impair fertility in males of reproductive potential. It is not known whether effects on fertility are reversible [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
The safety and effectiveness of Benznidazole Tablets have been established in pediatric patients 2 to 12 years of age for the treatment of Chagas disease. Use in pediatric patients 2 to 12 years of age was established in two adequate and well-controlled trials in pediatric patients 6 to 12 years old with additional safety and pharmacokinetic data from pediatric patients 2 to 6 years of age. [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Studies (14)].
Safety and effectiveness in pediatric patients below the age of 2 years and above the age of 12 years have not been established.
8.6 Hepatic Impairment
Use of Benznidazole Tablets has not been eva luated in patients with hepatic impairment.
8.7 Renal Impairment
Use of Benznidazole Tablets has not been eva luated in patients with renal impairment.
11 DESCRIPTION
Benznidazole Tablets contain benznidazole, a nitroimidazole antimicrobial. The chemical name of benznidazole is N-benzyl-2-(2-nitro-1H-imidazol-1-yl) acetamide. The empirical formula is C12H12N4O3 and the molecular weight is 260.246 g/mol. The structural formula is:
Structural Formula
Figure 1: Benznidazole Structure
Benznidazole is a yellowish, practically crystalline powder that is practically insoluble in water, sparingly soluble in acetone and ethanol, and slightly soluble in methanol.
Benznidazole Tablets are white round tablets each containing 12.5 mg or 100 mg of benznidazole, for oral use. The 100 mg white tablets are round and functionally scored twice as a cross on both sides debossed with “E” on one side of each quarter portion. The 12.5 mg white tablets are round and unscored debossed with “E” on one side.
The inactive ingredients are as follows: magnesium stearate, NF; microcrystalline cellulose, NF; monohydrate lactose, NF; pre-gelatinized corn starch, NF; and sodium croscarmellose, NF.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Benznidazole is a nitroimidazole antimicrobial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
The pharmacodynamics of benznidazole is unknown.
12.3 Pharmacokinetics
Absorption
The absorption of benznidazole from three different 100 mg benznidazole preparations was comparable when administered as a single dose under fasting conditions in adult healthy volunt |
