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Benznidazole 12.5 mg Tablet, 100-count — NDC 00642-7463-12 package photo

Benznidazole 12.5 mg Tablet, 100-count

by Exeltis USA, Inc. · 1 BOTTLE in 1 CARTON (0642-7463-12) / 100 TABLET in 1 BOTTLE
NDC 00642-7463-12
🏷️ FDA NDC (as labeled) 0642-7463-12 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 10, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 0642-7463-12
Product NDC 0642-7463
11-digit billing NDC 00642746312
NCPDP billing unit EA — each (per item)
RxCUI 430551, 1993222
UNII YC42NRJ1ZD
UPC 0306427463122, 0306427464105
Application # NDA209570
SPL Set ID 8983d6a0-f63f-4f8e-bba4-38223f39e29b
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2018-03-30
Route ORAL
Dosage form TABLET
Substance BENZNIDAZOLE
GCN Seq No 077693
GCN 43796
HICL code 021759
Ingredient (HICL) Benznidazole
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W4
Therapeutic class — intermediate (HIC2) Antiparasitics
HIC3 code W4K
Therapeutic class — specific (HIC3) Antiprotozoal Drugs,Miscellaneous
AHFS code 08:30.16.04
AHFS class Nitroimidazole Derivative, Trypanocidal
FDB label name BENZNIDAZOLE 12.5 MG TABLET
FDB brand name Benznidazole
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0642-7463-12 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00642-7463-12. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Nitroimidazole derivatives class.

Drug family (ATC) Nitroimidazole derivatives
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerExeltis USA, Inc.
Application holderCHEMO RESEARCH SL
FDA applicationNDA209570 (NDA)
Labeler code00642
First marketedMar 2018
Product typeHuman Prescription Drug
Portfolio10 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name BENZNIDAZOLE 12.5 MG TABLET Ingredient Benznidazole
📖 What it is MedlinePlus · NLM

Benznidazole is used to treat Chagas disease (caused by a parasite) in children 2 to 12 years old. Benznidazole is in a class of medications called antiprotozoals. It works by killing the organism that can cause Chagas disease.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Chagas disease is a parasitic infection caused by a tiny organism called Trypanosoma cruzi, usually spread through insect bites. Benznidazole is an antibiotic that targets this par...
  • What is benznidazole actually treating? My child tested positive for something called Chagas disease.
  • Not necessarily. The 100 mg tablets are scored, so they can be split into smaller pieces for an accurate weight-based dose. Both the 12.5 mg and 100 mg tablets can also be dissolve...
  • How do I give this to my child — do they have to swallow a whole tablet?
📖 Read our full Benznidazole guide →
7
Nutrient depletion considerations

Benznidazole may be associated with lower levels of 7 nutrients — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Benznidazole nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color white
ShapeRound
ImprintE
Size1 mm
ScoringScored — splits in 4
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Benznidazole 12.5 mgthis 00642-7463-12 Exeltis 100 tablets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2018
On the market since
Mar 2018
📍
2026
Currently FDA-listed
8 years listed
🔒
·
No generic listed yet
brand only
ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Benznidazole — the ingredient across all brands.

Top reported reactions

Rash18
American Trypanosomiasis16
Nausea10
Drug Interaction9
Headache8
Dizziness5
Hepatotoxicity5

Age at onset

Adult14
Elderly3

Reporter sex

100 reports
Male · 39%
Female · 61%

Serious outcomes

Hospitalization27
Death5
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 21 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00642-7463-12 You're viewing this 1 BOTTLE in 1 CARTON (0642-7463-12) / 100 TABLET in 1 BOTTLE 2018-03-30 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0642-7463-12, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00642-7463-12, written without dashes as 00642746312. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00642-7463-12, the first segment (00642) is the labeler code FDA assigned to Exeltis USA, Inc.; the middle segment (7463) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (12) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Exeltis USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Exeltis USA, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 166 words ▾

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 ~3 min read ▾

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 ).

2.1Important 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 )] .

2.2Recommended 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

2.3Assessment 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 )] .

2.4Preparation 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 in the cup over a period of approximately 1-2 minutes. Shake the contents of the cup gently to mix.

Drink the contents of the cup (slurry of tablets with water) immediately. Rinse the cup with an additional 10 mL of water and drink the whole amount. B.

Preparation of Slurry Using Benznidazole Tablets 100 mg for the Pediatric Population with Body Weight (30 kg or greater) Benznidazole Tablets 100 mg may be made into a slurry in a specified volume of water for the pediatric population with body weight of 30 kg or greater (see Table 3 ). The 100 mg tablet slurry is prepared as follows: Table 3: Preparation and Administration of Slurry Using Benznidazole Tablets 100 mg for the Pediatric Population with Body Weight 30 kg or greater Place the prescribed dose of Benznidazole Tablets 100 mg tablets into a cup.

Add the specified volume of water per number of 100 mg tablets as shown below. Body Weight Range (kg) Dose (mg) Number of Benznidazole Tablets 100 mg Quantity of Water for Preparing the…

💊 Dosage Forms and Strengths 72 words ▾

3 DOSAGE FORMS AND STRENGTHS Benznidazole Tablets are available as 100 mg and 12.5 mg tablets. 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. Tablets: 100 mg (functionally scored) ( 3 ). Tablets: 12.5 mg ( 3 ).

⛔ Contraindications 158 words ▾

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 ).

4.1Hypersensitivity 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 )] .

4.2Disulfiram Benznidazole Tablets are contraindicated in patients who have taken disulfiram within the last two weeks. Psychotic reactions may occur in patients who are using benznidazole and disulfiram concurrently [see Drug Interactions ( 7.1 )] .

4.3Patients with Cockayne Syndrome Benznidazole Tablets are contraindicated in patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole, another nitroimidazole drug, structurally related to benznidazole in patients with Cockayne syndrome [see Adverse Reactions ( 6.2 )] .

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Potential Risk for Genotoxicity and Carcinogenicity ( 5.1 ). Embryo-Fetal Toxicity: Can cause fetal harm. Pregnancy testing is recommended for females of reproductive potential.

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception ( 2.3 , 5.2 , 8.1 , 8.3 ). Hypersensitivity skin reactions have been reported with benznidazole. In case of skin reactions, presenting with additional symptoms of systemic involvement such as lymphadenopathy, fever and/or purpura, discontinuation of treatment is recommended ( 5.3 ).

Treatment with Benznidazole Tablets can potentially cause paresthesia or symptoms of peripheral neuropathy. In cases where neurological symptoms occur, immediate discontinuation of treatment is recommended ( 5.4 ). There have been hematological manifestations of bone marrow depression, such as neutropenia, thrombocytopenia, anemia, and leukopenia ( 5.5 ).

5.1Potential for Genotoxicity and Carcinogenicity Genotoxicity Genotoxicity of benznidazole has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodents [see Nonclinical Toxicology ( 13.1 )] . A study evaluating the cytogenetic effect of benznidazole in pediatric patients ranging from 11 months to 11 years of age (the safety and effectiveness of Benznidazole Tablets in patients less than 2 years old has not been established) with Chagas disease demonstrated a two-fold increase in chromosomal aberrations.

In pediatric patients with Chagas disease who were treated with benznidazole, the median incidence of micronucleated interphase lymphocytes in 20 patients increased 2-fold compared to pre-dose values. In the same study, the mean incidence of chromosomal aberrations in 10 patients also increased 2-fold compared to pre-dose values. Carcinogenicity Carcinogenicity has been observed in mice and rats treated chronically with nitroimidazole agents which are structurally similar to benznidazole.

Similar data have not been reported for benznidazole [see Nonclinical Toxicology ( 13.1 )] . It is not known whether benznidazole is associated with carcinogenicity in humans.

5.2Embryo-Fetal Toxicity Based on findings from animal studies, Benznidazole Tablets can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, benznidazole administered orally to pregnant rats and rabbits during organogenesis was associated with fetal malformations at doses approximately 1-3 times the maximum recommended human dose (MRHD) in rats (anasarca, anophthalmia, and/or microphthalmia) and doses approximately 0.3-1 times the MRHD in rabbits (ventricular septal defect). In rats, reduced maternal weights and smaller litter sizes occurred at a dose approximately 3 times the MRHD.

In rabbits, reduced maternal weight gain, and abortions in 2/20 females occurred at a dose approximately equal to the MHRD [see Use in Specific Populations ( 8.1 )] . Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential [see Dosage and Administration ( 2.3 )] .

Advise females of reproductive potential to use effective contraception during treatment with Benznidazole Tablets and for 5 days after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.3 )] .

5.3Hypersensitivity Skin Reactions Serious skin and subcutaneous disorders including acute generalized exanthematous pustulosis (AGEP), toxic epidermal necrolysis (TEN), erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with benznidazole. Discontinue treatment at the first evidence of these serious cutaneous reactions [see Adverse Reactions ( 6.2 )] . Extensive skin reactions, such as rash (maculopapular, pruritic macules, eczema, pustules, erythematous, generalized, and allergic dermatitis, exfoliative dermatitis) have also been reported.

M…

🤒 Adverse Reactions ~3 min read ▾

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.

6.1Clinical 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 reaction…

🔄 Drug Interactions 102 words ▾

7 DRUG INTERACTIONS

7.1Disulfiram 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 )] .

7.2Alcohol 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.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended ( 8.2 ).

8.1Pregnancy 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 inconsistent, treatment of chronic Chagas disease during pregnancy is not recommended due to risk of embryo-fetal toxicity from Benznidazole Tablets. Acute symptomatic Chagas disease is rare in pregnant women; however, symptoms may be serious or life-threatening.

There have been reports of pregnant women with life-threatening symptoms associated with acute Chagas disease who were treated with benznidazole. If a pregnant woman presents with acute symptomatic Chagas disease, the risks versus benefits of treatment with Benznidazole Tablets to the mother and the fetus should be evaluated on a case-by-case basis. Data Animal Data In an embryo-fetal toxicity study in pregnant rats, benznidazole was administered in oral doses of 15, 50, and 150 mg/kg/day during organogenesis (days 6-17 of gestation), and the high dose 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). No maternal toxicity was observed at a benznidazole dose of 50 mg/kg/day (approximately equal to the MRHD based on body surface area comparison), and no fetal toxicity was observed at a dose of 15 mg/kg/day (approximately equivalent to 0.3 times the MRHD based on whole body surface area comparison).

In an embryo-fetal study in pregnant rabbits benznidazole administered by oral (gavage) in doses of 2.5, 7.5, and 25 mg/kg/day during organogenesis (days 6 to 19 of gestation) was associated with maternal toxicity at the high dose, including reduced weight gain and food consumption and abortions in 2/20 females. Benznidazole was also…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy 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 inconsistent, treatment of chronic Chagas disease during pregnancy is not recommended due to risk of embryo-fetal toxicity from Benznidazole Tablets. Acute symptomatic Chagas disease is rare in pregnant women; however, symptoms may be serious or life-threatening.

There have been reports of pregnant women with life-threatening symptoms associated with acute Chagas disease who were treated with benznidazole. If a pregnant woman presents with acute symptomatic Chagas disease, the risks versus benefits of treatment with Benznidazole Tablets to the mother and the fetus should be evaluated on a case-by-case basis. Data Animal Data In an embryo-fetal toxicity study in pregnant rats, benznidazole was administered in oral doses of 15, 50, and 150 mg/kg/day during organogenesis (days 6-17 of gestation), and the high dose 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). No maternal toxicity was observed at a benznidazole dose of 50 mg/kg/day (approximately equal to the MRHD based on body surface area comparison), and no fetal toxicity was observed at a dose of 15 mg/kg/day (approximately equivalent to 0.3 times the MRHD based on whole body surface area comparison).

In an embryo-fetal study in pregnant rabbits benznidazole administered by oral (gavage) in doses of 2.5, 7.5, and 25 mg/kg/day during organogenesis (days 6 to 19 of gestation) was associated with maternal toxicity at the high dose, 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…

🧒 Pediatric Use 110 words ▾

8.4Pediatric 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.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Benznidazole is a nitroimidazole antimicrobial drug [see Microbiology ( 12.4 )] .

12.2Pharmacodynamics The pharmacodynamics of benznidazole is unknown.

12.3Pharmacokinetics 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. Preparations for 100 mg Benznidazole Oral Dose One Benznidazole 100 mg Tablet Taken Whole Slurry prepared with one Benznidazole 100 mg Tablet Slurry prepared with eight Benznidazole 12.5 mg Tablets Parameter Mean (SD) Mean (SD) Mean (SD) Cmax (mg/L) 2.4 (0.5) 2.4 (0.4) 2.4 (0.4) Tmax a(h) 2 (1-4) 2 (0.5-4) 2 (1 - 4.5) AUC (mg*h/L) 43.5 (9.0) 41.8 (9.6) 44.1 (11.8) a Tmax is presented as median (range) Effect of Food Benznidazole Cmax and AUC were not affected by the administration of Benznidazole 100 mg tablet with a high-fat, high-caloric meal (approximately 1034 total kcal, 67 kcal from fat, 42 kcal from carbohydrates, 59 kcal from protein) compared with fasted conditions in adult healthy volunteers.

Serum concentrations of benznidazole reached peak levels at 3.2 hours (1-10 hours) after administration of Benznidazole Tablets 100 mg tablet after a high-fat, high-caloric meal, and at 2.0 hours (0.5-4 hours) in fasted conditions [see Dosage and Administration ( 2.1 )] . Distribution Protein binding is reported to be approximately 44 to 60 %. The mean blood:plasma radioactivity ratios, ranging from 0.63 to 1.10, suggest that there is no preferential distribution of benznidazole into the red blood cells.

The apparent volume of distribution of benznidazole is approximately 45 L. Elimination The elimination half-life of benznidazole is approximately 13 hours in healthy volunteers following single dose. The apparent total clearance of benznidazole is about

2.3L/h. Metabolism In plasma, benznidazole parent drug is the most abundant component, accounting for approximately 80% of the total drug related exposure and no major circulating metabolites were identified. The primary benznidazole metabolism pathway is indicated to be nitro reduction followed by glucuronidation.

Excretion Following oral administration of 100 mg radiolabeled benznidazole, about 68% and 21% of the radioactivity is recovered in urine (6% of total dose as unchanged parent drug) and feces (unchanged parent drug not detected), respectively. Specific Populations The effect of sex, race, renal impairment, or hepatic impairment on the pharmacokinetics of benznidazole is unknown. Drug Interaction Studies In vitro studies showed that benznidazole is a P-gp substrate and does not notably induce Cytochrome P450 enzymes 1A2, 2B6, and 3A4 at concentrations up to 100 mcM.

12.4Microbiology Mechanism of Action Benznidazole inhibits the synthesis of DNA, RNA, and proteins within the T. cruzi parasite. Studies suggest that benznidazole is reduced by a Type I nitroreductase (NTR) enzyme of T. cruzi producing a series of short-lived intermediates that may promote damage to several macromolecules including DNA. In mammalian cells, however, benznidazole is metabolized by reduction of the nitro group to an amino group by a Type II NTR enzyme.

The precise mechanism of action is not known. Antimicrobial Activity Benznidazole is active against all three stages, trypomastigotes, amastigotes, and epimastigotes, of T. cruzi . However, the sensitivity of T. cruzi strains to benznidazole, from different geographic regions, may vary.

Resistance Studies in vitro and in mice infected with T. cruzi suggest a potential for development of resistance to benznidazole. The mechanisms of drug resistance appear to be multifactorial. These mechanisms include decreased activity due to a mutatio…

🧬 Mechanism of Action 16 words ▾

12.1Mechanism of Action Benznidazole is a nitroimidazole antimicrobial drug [see Microbiology ( 12.4 )] .

📦 How Supplied / Storage and Handling 136 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How 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).

16.2Storage 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.

📦 Storage and Handling 37 words ▾

16.2Storage 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.

📋 Description 152 words ▾

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

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Instructions for Use ). Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that exposure to Benznidazole Tablets during pregnancy can result in fetal harm. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1 )] .

Advise females of reproductive potential to use effective contraception while taking Benznidazole Tablets and for 5 days after the last dose [see Use in Specific Populations ( 8.3 )] . Lactation Advise women not to breastfeed during treatment with Benznidazole Tablets [see Use in Specific Populations ( 8.2 )] . Infertility Advise males of reproductive potential that Benznidazole Tablets may impair fertility [see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.1 )] .

Important Administration Instructions Advise patients and parents/caregivers of pediatric patients taking Benznidazole Tablets that: •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. •Benznidazole Tablets 12.5 mg and 100 mg (whole or split) can be made into a slurry in a specified volume of water for the pediatric population [see Dosage and Administration ( 2.3 )] . Hypersensitivity Skin Reactions Advise patients that serious skin reactions can occur with Benznidazole Tablets.

In case of skin reactions, presenting with additional symptoms of systemic involvement such as lymphadenopathy, fever and/or purpura, discontinuation of treatment is necessary. Central and Peripheral Nervous System Effects Advise patients that treatment can potentially cause paresthesia or symptoms of peripheral neuropathy. In cases where neurological symptoms occur, immediate discontinuation of treatment is recommended.

Hematological Manifestations of Bone Marrow Depression Advise patients that there have been hematological manifestations of bone marrow depression, such as anemia and leukopenia, which are reversible, and normalized after treatment discontinuation. Manufactured for Chemo Research, S.L. Madrid, Spain Manufactured by Laboratorios Liconsa S.A.

Guadalajara, Spain Distributed by: Exeltis USA, Inc. Florham Park, NJ 07932 exeltis

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 00642-0207-03 · Exeltis 00642-7464-10 · Exeltis →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.