Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 12.5 mg, 100 mg
Pharmacology
Mechanism of Action
Inhibits the synthesis of DNA, RNA, and proteins within the T. cruzi parasite.
Pharmacokinetics/Pharmacodynamics
Absorption
Rapid (Bern 2007)
Distribution
Vd = 45 L.
Metabolism
Nitro reduction followed by glucuronidation
Excretion
Urine (~68%) and feces (~21%).
Time to Peak
Median: 2 hours
Half-Life Elimination
~13 hours
Protein Binding
~44% to 60%
Use: Labeled Indications
Chagas disease: Treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi in pediatric patients 2 to 12 years of age.
Contraindications
Hypersensitivity to benznidazole, other nitroimidazole derivatives, or any component of the formulation; disulfiram within previous 2 weeks of benznidazole therapy.
Dosage and Administration
Dosing: Adult
Chagas disease (off-label): Oral: 5 to 7 mg/kg/day in 2 divided doses for 60 days (Bern 2007; CDC 2017). Alternatively, 5 mg/kg/day in 2 divided doses (maximum dose: 300 mg/day) for 60 days; for patients weighing >60 kg, the total dose expected should be calculated, extending the treatment time beyond 60 days (eg, patients weighing 65 kg receive 300 mg/day for 65 days; patients weighing 70 kg received 300 mg/day for 70 days) (AHA [Nunes 2018]; Andrade 2011).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Chagas disease:
Children ≥2 years to 12 years: Oral:
Weight-based dosing: 5 to 8 mg/kg/day in 2 divided doses administered every 12 hours for 60 days.
Fixed dosing:
<15 kg: 50 mg every 12 hours for 60 days.
15 to <20 kg: 62.5 mg every 12 hours for 60 days.
20 to <30 kg: 75 mg every 12 hours for 60 days.
30 to <40 kg: 100 mg every 12 hours for 60 days.
40 to <60 kg: 150 mg every 12 hours for 60 days.
≥60 kg: 200 mg every 12 hours for 60 days.
Children >12 years and Adolescents: Limited data available: Oral: 5 to 7 mg/kg/day in 2 divided doses for 60 days; Note: May also be administered in 3 divided doses (Red Book [AAP 2018]).
Administration
Oral: Administer with or without food, approximately 12 hours apart.
To make slurry using 12.5 or 100 mg tablets:
Place prescribed dose in a cup and add the specified volume of water (also refer to manufacturer's labeling):
12.5 mg tablets: 40 mL for 4 tablets, 50 mL for 5 tablets, or 60 mL for 6 tablets
100 mg tablets: 80 mL for 1 tablet, 120 mL for 1.5 tablets, or 160 mL for 2 tablets
Allow tablets to disintegrate over 1 to 2 minutes. Shake cup gently to mix and administer contents immediately. For 12.5 mg tablets, rinse cup with an additional 10 mL of water and administer entire amount. For 100 mg tablets, rinse cup with an additional 80 mL of water and administer entire amount; repeat this rinse with 80 mL and drink again.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Drug Interactions
Disulfiram: Benznidazole may enhance the adverse/toxic effect of Disulfiram. In particular, the risk for CNS toxicities such as psychosis may be increased. Avoid combination
Adverse Reactions
>10%:
Dermatologic: Skin rash (16%), skin lesion (11%)
Endocrine & metabolic: Weight loss (13%)
Gastrointestinal: Abdominal pain (25%), decreased appetite (5%)
1% to 10%:
Central nervous system: Headache (7%), peripheral neuropathy (2%)
Gastrointestinal: Nausea (5%), vomiting (5%), anorexia (<5%), diarrhea (4%)
Hepatic: Increased serum transaminases (5%)
Neuromuscular & skeletal: Arthralgia (<5%), tremor (2%)
<1%, postmarketing, and/or case reports: Acute generalized exanthematous pustulosis, ageusia, agranulocytosis, amnesia, arthritis, disorientation, dress syndrome, edema, epigastric pain, erythema multiforme, erythematous plaques, erythematous rash, exfoliation of skin, exfoliative dermatitis, eyelid edema, fatigue, fever, granulocytopenia, headache, hepatitis, hypoesthesia, increased serum alkaline phosphatase, increased serum bilirubin, insomnia, lack of concentration, lymphadenopathy, maculopapular rash, musculoskeletal pain, myalgia, paresthesia, pruritic rash, seizure, skin blister, swelling of extremities, thrombocytopenia, toxic epidermal necrolysis, toxic hepatitis, weakness, xerostomia
Warnings/Precautions
Concerns related to adverse effects:
- Carcinogenic/genotoxic: Carcinogenicity has been observed in mice and rats with nitroimidazole agents that are structurally similar to benznidazole in animal studies; it is unknown whether benznidazole is associated with carcinogenicity in humans. Genotoxicity (two-fold increase in chromosomal aberrations) of benznidazole has been demonstrated in one study of pediatric patients (11 months to 11 years) with Chagas disease.
- CNS effects: Paresthesia and/or peripheral neuropathy have been reported and may take several months to resolve; in general, these symptoms occur late in the course of treatment. Headache and dizziness have also been reported. Discontinue treatment if neurologic signs or symptoms occur.
- Dermatologic reactions: Serious skin and subcutaneous disorders (eg, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms) have been reported. Extensive skin reactions (eg, rash [maculopapular, pruritic macules, eczema, pustules, erythematous, generalized], allergic dermatitis, exfoliative dermatitis) have also been reported, most cases occurring after ~10 days of treatment; most rashes resolved with treatment discontinuation. Mild to moderate dermatitis may be controlled with prednisone (AHA [Nunes 2018]). Discontinue treatment at first evidence of a serious cutaneous reaction or skin reactions presenting with systemic signs/symptoms (eg, lymphadenopathy, fever, purpura).
- Hematologic effects: Bone marrow depression (eg, neutropenia, thrombocytopenia, anemia, leukopenia) that resolved after treatment discontinuation has been reported. Use benznidazole with caution and under strict medical supervision in patients with hematological manifestations of bone marrow depression. Monitor CBC, as well as total and differential leukocyte counts, prior to initiation, during treatment, and after discontinuation of treatment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitoring Parameters
CBC and total and differential leukocyte counts prior to initiation, during treatment (approximately 21 days after the initiation of benznidazole), and after discontinuation; pregnancy test prior to initiation in female patients; signs of skin rash or neurologic signs/symptoms during treatment (manufacturer’s labeling; AHA [Nunes 2018])
Pregnancy
Pregnancy Considerations
Information related to the use of benznidazole for the treatment of acute Chagas disease in pregnant women is limited; treatment of chronic disease during pregnancy is not recommended.
Congenital transmission of Chagas disease may occur and the actual risk may depend on stage of maternal disease and geographic location (Bittencourt 1992). There are no specific recommendations for preventing vertical transmission of disease in women who are already pregnant. Because treatment is associated with a high risk of adverse events in adults and there is lack of data on possible teratogenic effects, treatment during pregnancy is not currently recommended (Carlier 2011). However, therapy with benznidazole prior to pregnancy in women who test positive for Trypanosoma cruzi antibodies may be used to prevent congenital transmission (Álvarez 2017; Carlier 2011).
Females of reproductive potential should have a pregnancy test prior to therapy. Effective contraception should be used during treatment and for 5 days after the last dose.
Patient Education
What is this drug used for?
- It is used to treat Chagas disease.
Frequently reported side effects of this drug
- Abdominal pain
- Weight loss
- Nausea
- Vomiting
- Lack of appetite
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Burning or numbness feeling
- Headache
- Dizziness
- Swollen glands
- Toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
- Infection
- Bruising
- Bleeding
- Severe loss of strength and energy
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
