Benznidazole
FDA Drug Information • Also known as: Benznidazole
- Brand Names
- Benznidazole
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
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 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. structure
What Is Benznidazole Used For?
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. Benznidazole Tablets, a nitroimidazole antimicrobial, is indicated in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis), caused by Trypanosoma cruzi ( 1 ). 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 . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials ( 1 , 14 ).
Dosage and Administration
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 )] . Benznidazole Tablets 100 mg are functionally scored tablets which can be split into one-half (50 mg) or one-quarter (25 mg) at the scored lines to provide doses less than 100 mg [see Instructions for Use ] . Benznidazole Tablets 12.5 mg and 100 mg can be made into slurry as an alternative method of administration [see Dosage and Administration ( 2.4 )] . 2.2 Recommended Dosage in Pediatric Patients (2 to 12 Years of Age) The total daily dose for pediatric patients 2 to 12 years of age 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 (see Table 1 ). Table 1: Recommended Dosage of Benznidazole Tablets in Pediatric Patients (2 to 12 Years of Age) Body Weight Range (kg) Dose (mg) Number of Benznidazole Tablets 12.5 mg Number of Benznidazole Tablets 100mg Duration and Frequency of Therapy Less than 15 kg 50 mg 4 tablets ½ tablet Administered twice daily approximately 12 hours apart for 60 days. 15 kg to less than 20 kg 62.5 mg 5 tablets 20 kg to less than 30 kg 75 mg 6 tablets ¾ tablet 30 kg to less than 40 kg 100 mg 1 tablet 40 kg to less than 60 kg 150 mg 1 ½ tablets Greater than or equal to 60 kg 200 mg 2 tablets 2.3 Assessment Prior to Initiating Benznidazole Tablets Obtain a pregnancy test in females of reproductive potential prior to therapy with Benznidazole Tablets [see Use is Specific Populations ( 8.3 )] . 2.4 Preparation of Slurry as an Alternative Method of Administration A. Preparation of Slurry Using Benznidazole Tablets 12.5 mg for the Pediatric Population with Body Weight Less Than 30 kg Benznidazole Tablets 12.5 mg may be made into slurry in a specified volume of water for the pediatric population with body weight less than 30 kg (see Table 2 ). The 12.5 mg tablet slurry is prepared by the following method: Table 2: Preparation and Administration of Slurry Using Benznidazole Tablets 12.5 mg for the Pediatric Population with Body Weight of Less than 30 kg Place the prescribed dose of Benznidazole Tablets 12.5 mg into a cup. Add the specified volume of water per number of 12.5 mg tablets as shown below. Body Weight Range (kg) Dose (mg) Number of Benznidazole Tablets 12.5 mg Quantity of Water for Preparing the Slurry Less than 15 kg 50 mg 4 tablets 40 mL 15 kg to less than 20 kg 62.5 mg 5 tablets 50 mL 20 kg to less than 30 kg 75 mg 6 tablets 60 mL Allow the tablets to disintegrate...
Side Effects (Adverse Reactions)
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 ( 5.5 )] Most common adverse reactions observed were abdominal pain, rash, decreased weight, headache, nausea, vomiting, neutropenia, urticaria, pruritus, eosinophilia, decreased appetite ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Exeltis USA, Inc. at 1-877-324-9349 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Benznidazole was evaluated in two randomized, double-blind, placebo-controlled trials (Trial 1 1 and Trial 2 2 ) and one uncontrolled trial (Trial 3 3 ). Trial 1 was conducted in pediatric patients 6 to 12 years of age with chronic indeterminate Chagas disease in Argentina. The chronic indeterminate form 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 twice daily for 60 days; N= 55) or placebo (N=51) and followed for 4 years. Trial 2 was conducted in pediatric patients 7 to 12 years of age with chronic indeterminate Chagas disease in Brazil. A total of 129 patients were randomized to receive either benznidazole (7.5 mg/kg/day twice daily for 60 days; N = 64) or placebo (N = 65) and followed for 3 years. Trial 3 was an uncontrolled study in pediatric patients 2 to 12 years of age with chronic indeterminate Chagas disease. A total of 37 pediatric patients with Chagas disease were enrolled in this safety and pharmacokinetics study. Patients were treated with benznidazole 5 to 8 mg/kg/day twice daily for 60 days. Adverse Reactions Leading to Discontinuation In Trial 1, benznidazole was discontinued due to an adverse reaction in 5/55 (9%) patients. Some patients had more than one adverse reaction resulting in treatment discontinuation. The adverse reactions included abdominal pain, nausea, vomiting, rash, decreased appetite, headache, and transaminases increased. Common Adverse Reactions in Pediatric Patients The most frequently reported adverse reactions in pediatric patients treated with benznidazole in Trial 1 were abdominal pain (25%), rash (16%), decreased weight (13%), and headache (7%). Table 4 lists adverse reactions occurring at a rate of 1% or greater in pediatric patients with Chagas disease aged 6 to 12 years of age in Trial 1. Table 4: Adverse Reactions Occurring in Pediatric Patients with Chagas Disease aged 6 to 12 Years in Trial 1 Body System Adverse Reaction Benznidazole (N=55) N (%) Placebo (N=51) N (%) Gastrointestinal Abdominal pain 14 (25) 4 (8) Weight decreased 7 (13) 1 (2) Nausea 3 (5) 1 (2) Vomiting 3 (5) 0 Diarrhea 2 (4) 0 Decreased appetite 3 (5) 0 Skin and subcutaneous tissue Rash 9 (16) 0 Metabolism/Laboratory Transaminases increased 3 (5) 0 Nervous system Disorders Dizziness 2 (4) 2 (4) Peripheral neuropathy 1 (2) 0 Tremor 1 (2) 0 In Trial 2, skin lesions were reported in 7 of 64 (11%) pediatric patients treated with benznidazole and in 2 of 65 patients receiving placebo. Adverse reactions reported in fewer than 5% of benznidazole-treated patients included nausea, anorexia, headache, abdominal pain and arthralgia. In a subset of 19 pediatric patients 2 to 6 years of age treated with benznidazole in Trial 3, 6 patients (32%) had the following adverse...
Drug 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). Benznidazole Tablets are not expected to cause alcohol aversion or a disulfiram-like reaction as a result of ethanol ingestion.
Contraindications
4 CONTRAINDICATIONS
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies, Benznidazole Tablets may cause fetal harm when administered to a pregnant woman. Published postmarketing reports on benznidazole use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes. There are risks to the fetus associated with Chagas Disease (see Clinical Considerations ) . In embryo-fetal development studies, benznidazole administered orally to pregnant rats and rabbits during organogenesis was associated with fetal malformations at doses approximately 1-3 times the MRHD in rats (anasarca, anophthalmia, and/or microphthalmia) and doses approximately 0.3-1.0 times the MRHD in rabbits (ventricular septal defect). In pregnant rats administered benznidazole during gestation and through lactation, effects in first generation offspring included reduced fertility in individual males and reduced numbers of live embryos and fetuses in pregnant females at a maternal dose equivalent to approximately 1.5 times the MRHD (see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk Published data from case-control and observational studies on chronic Chagas disease during pregnancy are inconsistent in their findings. Some studies showed an increased risk of pregnancy loss, prematurity and neonatal mortality in pregnant women who have chronic Chagas disease while other studies did not demonstrate these findings. Chronic Chagas disease is usually not life-threatening. Since pregnancy findings are...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Benznidazole Tablets (12.5 mg or 100 mg) are supplied as follows: 100 mg white tablets, round and functionally scored twice as a cross on both sides. Each tablet is about 10 mm in diameter debossed with “E” on one side of each quarter portion. 12.5 mg white tablets, round and unscored. Each tablet is about 5 mm in diameter debossed with “E” on one side. Benznidazole Tablets 100 mg are available in bottles of 100 tablets (NDC 0642-7464-10). Benznidazole Tablets 12.5 mg are available in bottles of 100 tablets (NDC 0642-7463-12). 16.2 Storage and Handling Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep bottle tightly closed and protect from moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.