Identification
- Summary
Benznidazole is a trypanocidal agent used to treat Chagas disease.
- Generic Name
- Benznidazole
- DrugBank Accession Number
- DB11989
- Background
Benznidazole was granted accelerated approval for the treatment of Chagas disease in children 2-12 years of age by the FDA on August 29, 2017.9 It is the first treatment made available in the United States for Chagas disease.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Benznidazole (DB11989)
- Weight
- Average: 260.253
Monoisotopic: 260.090940262 - Chemical Formula
- C12H12N4O3
- Synonyms
- Benznidazol
- Benznidazole
- Benznidazolum
- External IDs
- NSC-299972
- RO 07-1051
- Ro 71051
Pharmacology
- Indication
For use in the treatment of Chagas disease in children 2-12 years of age 9.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Benznidazole is a trypanocidal agent which kills the causative organism in Chagas disease, Trypanosoma cruzi 1.
- Mechanism of action
Benznidazole is thought to be reduced to various electrophilic metabolites by nitroreductases present in Trypanosoma cruzi 1. These metabolites likely bind to proteins, lipids, DNA, and RNA resulting in damage to these macromolecules. Benznidazole has been found to increase trypanosomal death through interferon-γ which is likely present in increased amounts due to inflammation caused by macromolecule damage 3. DNA in parasites affected by benznidazole has been found to undergo extensive unpacking with overexpression of DNA repair proteins supporting the idea of DNA damage contributing to the mechanism of the drug 2.
- Absorption
Benznidazole has a bioavailability of 91.7% and a Tmax of 2.93 h 4,5.
- Volume of distribution
The apparent volume of distribution is 39.19 L 5.
- Protein binding
Not Available
- Metabolism
Benznidazole is metabolized by nitroreductases in Trypanosoma cruzi and by cytochrome P450 enzymes 5,6.
- Route of elimination
The metabolites of benznidazole appear to be primarily exreted in the urine 6.
- Half-life
The half life of elimination is 13.27 h 5.
- Clearance
The apparent oral clearance is 2.04 L/h 5.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
At clinically relevant dosages, benznidazole can produce hepatotoxicity, peripheral neuropathy, and angioedema 7,8.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Benznidazole which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Benznidazole which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Benznidazole which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Benznidazole which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Benznidazole which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Benznidazole which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Benznidazole which could result in a higher serum level. Acrivastine Acrivastine may decrease the excretion rate of Benznidazole which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Benznidazole which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Benznidazole which could result in a higher serum level. 
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- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Benznidazole Tablet 12.5 mg/1 Oral Exeltis Usa, Inc. 2018-03-30 Not applicable US 
Benznidazole Tablet 100 mg/1 Oral Exeltis Usa, Inc. 2018-03-30 Not applicable US
Categories
- ATC Codes
- P01CA02 — Benznidazole
- Drug Categories
- Agents Against Leishmaniasis and Trypanosomiasis
- Anti-Infective Agents
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Drugs that are Mainly Renally Excreted
- Imidazoles
- Immunologic Factors
- Mutagens
- Nitro Compounds
- Nitroimidazole Antimicrobial
- Nitroimidazole Derivatives
- Noxae
- Toxic Actions
- Trypanocidal Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as nitroaromatic compounds. These are c-nitro compounds where the nitro group is C-substituted with an aromatic group.
- Kingdom
- Organic compounds
- Super Class
- Organic 1,3-dipolar compounds
- Class
- Allyl-type 1,3-dipolar organic compounds
- Sub Class
- Organic nitro compounds
- Direct Parent
- Nitroaromatic compounds
- Alternative Parents
- N-substituted imidazoles / Benzene and substituted derivatives / Heteroaromatic compounds / Secondary carboxylic acid amides / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic zwitterions show 3 more
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Azole / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Imidazole show 14 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Trypanosoma cruzi
Chemical Identifiers
- UNII
- YC42NRJ1ZD
- CAS number
- 22994-85-0
- InChI Key
- CULUWZNBISUWAS-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H12N4O3/c17-11(14-8-10-4-2-1-3-5-10)9-15-7-6-13-12(15)16(18)19/h1-7H,8-9H2,(H,14,17)
- IUPAC Name
- N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide
- SMILES
- [O-][N+](=O)C1=NC=CN1CC(=O)NCC1=CC=CC=C1
References
- General References
- Maya JD, Cassels BK, Iturriaga-Vasquez P, Ferreira J, Faundez M, Galanti N, Ferreira A, Morello A: Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol A Mol Integr Physiol. 2007 Apr;146(4):601-20. Epub 2006 Mar 12. [Article]
- Rajao MA, Furtado C, Alves CL, Passos-Silva DG, de Moura MB, Schamber-Reis BL, Kunrath-Lima M, Zuma AA, Vieira-da-Rocha JP, Garcia JB, Mendes IC, Pena SD, Macedo AM, Franco GR, de Souza-Pinto NC, de Medeiros MH, Cruz AK, Motta MC, Teixeira SM, Machado CR: Unveiling benznidazole's mechanism of action through overexpression of DNA repair proteins in Trypanosoma cruzi. Environ Mol Mutagen. 2014 May;55(4):309-21. doi: 10.1002/em.21839. Epub 2013 Dec 18. [Article]
- Romanha AJ, Alves RO, Murta SM, Silva JS, Ropert C, Gazzinelli RT: Experimental chemotherapy against Trypanosoma cruzi infection: essential role of endogenous interferon-gamma in mediating parasitologic cure. J Infect Dis. 2002 Sep 15;186(6):823-8. Epub 2002 Aug 16. [Article]
- Raaflaub J, Ziegler WH: Single-dose pharmacokinetics of the trypanosomicide benznidazole in man. Arzneimittelforschung. 1979;29(10):1611-4. [Article]
- Wiens MO, Kanters S, Mills E, Peregrina Lucano AA, Gold S, Ayers D, Ferrero L, Krolewiecki A: Systematic Review and Meta-analysis of the Pharmacokinetics of Benznidazole in the Treatment of Chagas Disease. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7035-7042. Print 2016 Dec. [Article]
- Perin L, Moreira da Silva R, Fonseca KD, Cardoso JM, Mathias FA, Reis LE, Molina I, Correa-Oliveira R, Vieira PM, Carneiro CM: Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02410-16. doi: 10.1128/AAC.02410-16. Print 2017 Apr. [Article]
- Miller DA, Hernandez S, Rodriguez De Armas L, Eells SJ, Traina MM, Miller LG, Meymandi SK: Tolerance of benznidazole in a United States Chagas Disease clinic. Clin Infect Dis. 2015 Apr 15;60(8):1237-40. doi: 10.1093/cid/civ005. Epub 2015 Jan 18. [Article]
- Davies C, Dey N, Negrette OS, Parada LA, Basombrio MA, Garg NJ: Hepatotoxicity in mice of a novel anti-parasite drug candidate hydroxymethylnitrofurazone: a comparison with Benznidazole. PLoS Negl Trop Dis. 2014 Oct 16;8(10):e3231. doi: 10.1371/journal.pntd.0003231. eCollection 2014 Oct. [Article]
- FDA: Benznidazole Announcement [Link]
- FDA Approved Drug Products: Benznidazole tablets for oral use [Link]
- External Links
- KEGG Drug
- D02489
- PubChem Compound
- 31593
- PubChem Substance
- 347828309
- ChemSpider
- 29299
- BindingDB
- 50089916
- 18994
- ChEBI
- 133833
- ChEMBL
- CHEMBL110
- ZINC
- ZINC000000056949
- Wikipedia
- Benznidazole
- MSDS
- Download (133 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Diagnostic Chagas Disease 1 4 Completed Treatment Chagas Disease 2 3 Completed Treatment Cardiovascular Disease (CVD) / Chagas Disease / Trypanosomiasis 1 3 Completed Treatment Chagas Disease 1 3 Recruiting Treatment Chagas Disease 3 2 Active Not Recruiting Treatment Chagas Disease / Trypanosoma Cruzi Infection 1 2 Completed Treatment Chagas Disease 2 2 Unknown Status Treatment Chagas Disease 1 2 Unknown Status Treatment Chagas Disease / Trypanosoma Cruzi Infection 1 2 Unknown Status Treatment Chronic Chagas Disease, Indeterminate 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet Oral 100 mg/1 Tablet Oral 12.5 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 190-192 MSDS - Predicted Properties
Property Value Source Water Solubility 0.383 mg/mL ALOGPS logP 0.92 ALOGPS logP 1.32 Chemaxon logS -2.8 ALOGPS pKa (Strongest Acidic) 13.68 Chemaxon pKa (Strongest Basic) 0.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 90.06 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 67.12 m3·mol-1 Chemaxon Polarizability 24.96 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-00kf-7921100000-e7c8d6322a8bca6ef40f
Drug created at October 20, 2016 21:08 / Updated at January 02, 2022 10:33