Overview
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 C 12 H 12 N 4 O 3 and the molecular weight is 260.246 g/mol. The structural formula is: Figure 1: Benznidazole Structure Benznidazole is a yellowish, practically crystalline powder that is...
Mechanism of Action
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 volunteers ( Table 6 ). Table 6: Summary of Benznidazole Pharmacokinetic (PK) Parameters Following a Single Oral Dose of 100 mg Benznidazole Administered Under Fasting Conditions in Adult Healthy Volunteers.
Indications
- 1 INDICATIONS AND USAGE Benznidazole Tablets are indicated in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi . This indication is approved under accelerated approval based on the number of treated patients who became Immunoglobulin G (IgG) antibody negative against the recombinant antigens of T. cruzi [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Common Doses
- 5 mg
- 8 mg
- 12.5 mg
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION Pediatric patients 2 to 12 years of age: The total daily dose is 5 mg/kg to 8 mg/kg orally administered in two divided doses separated by approximately 12 hours for a duration of 60 days ( 2.2 ). See Full Prescribing Information for important administration instructions ( 2.1 , 2.3 , 2.4 ). 2.1 Important Administration Instructions Benznidazole Tablets (12.5 mg and 100 mg) are for oral use and may be taken with or without food [see Clinical Pharmacology ( 12.3 )] . Benznidazole Tablets are dosed by body weight (kg) [see Dosage and Administration ( 2.2 )] .
Contraindications
- 4 CONTRAINDICATIONS • History of hypersensitivity reaction to benznidazole or other nitroimidazole derivatives ( 4.1 ). • Disulfiram usage within the last two weeks ( 4.2 ). • Patients with Cockayne Syndrome ( 4.3 , 6.2 ). 4.1 Hypersensitivity Benznidazole Tablets are contraindicated in patients with a history of hypersensitivity reaction to benznidazole or other nitroimidazole derivatives. Reactions have included severe skin and soft tissue reactions [see Adverse Reactions ( 6.1 )] . 4.
Side Effects
- 6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling: Potential for Genotoxicity, Carcinogenicity, and Mutagenicity [see Warnings and Precautions ( 5.1 )] Hypersensitivity Skin Reactions [see Warnings and Precautions ( 5.3 )] Central and Peripheral Nervous System Effects [see Warnings and Precautions ( 5.4 )] Hematological Manifestations of Bone Marrow Depression [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS 7.1 Disulfiram Psychotic reactions have been reported in patients who are concurrently taking disulfiram and nitroimidazole agents (structurally related to benznidazole, but not with benznidazole). Benznidazole Tablets should not be given to patients who have taken disulfiram within the last two weeks [see Contraindications ( 4.2 )] . 7.2 Alcohol and Products Containing Propylene Glycol In vitro studies showed that benznidazole, at concentrations from 0.03 μM to 100 μM, does not inhibit the enzymatic activity of human alcohol dehydrogenase (ALDH).