Version May 2024
Chagas disease (off label): Oral: 5 to 7 mg/kg/day in 2 divided doses for 60 days (Ref). 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) (Ref). Note: For patients with HIV, 5 to 8 mg/kg/day in 2 divided doses is recommended for 30 to 60 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Benznidazole: Pediatric drug information")
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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity (eg, severe skin and soft tissue reactions) to benznidazole, other nitroimidazole derivatives, or any component of the formulation; use of disulfiram within previous 2 weeks of benznidazole therapy; Cockayne syndrome.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 12.5 mg, 100 mg
Yes
Tablets (Benznidazole Oral)
12.5 mg (per each): $3.00
100 mg (per each): $3.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
Oral: Administer with or without food, approximately 12 hours apart. 100 mg tablet is scored and may be split to allow for doses in increments of 25 mg and 50 mg.
Slurry preparation: Tablet strength used to make slurry is dependent on patient weight. Place prescribed dose in a cup and add the specified volume of water; allow tablets to disintegrate over 1 to 2 minutes. Shake cup gently to mix and administer contents immediately. Rinse cup with additional water and administer entire amount; volume of rinse is based on tablet strength used; for slurry made with 12.5 mg tablets, rinse with an additional 10 mL; for 100 mg tablets, rinse with an additional 80 mL and repeat rinse with a second 80 mL (refer to manufacturer's labeling for additional information).
Patient weight <30 kg: Use 12.5 mg tablets:
50 mg dose: Dissolve 4 tablets in 40 mL water
62.5 mg dose: Dissolve 5 tablets in 50 mL water
75 mg dose: Dissolve 6 tablets in 60 mL water
Patient weight ≥30 kg: Use 100 mg tablets:
100 mg dose: Dissolve 1 tablet in 80 mL water
150 mg dose: Dissolve 1.5 tablets in 120 mL water
200 mg dose: Dissolve 2 tablets in 160 mL water
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Benznidazole may cause carcinogenicity, teratogenicity (or other developmental toxicity), reproductive toxicity, and/or genotoxicity. Assess risk to determine appropriate containment strategy (USP-NF 2017).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, if unable to swallow whole), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid (NIOSH 2016).
Chagas disease: Treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi in pediatric patients 2 to 12 years of age.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Disulfiram: Benznidazole may enhance the adverse/toxic effect of Disulfiram. In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid combination
Patients who may become pregnant should have a pregnancy test prior to therapy. Effective contraception should be used during treatment and for 5 days after the last dose.
Therapy with benznidazole prior to pregnancy in patients who test positive for T. cruzi antibodies may prevent congenital transmission. Patients who may become pregnant should be treated prior to conception (Álvarez 2017; Carlier 2011; Meymandi 2018; Rios 2020).
Fetal malformations were observed following administration to pregnant rats and rabbits at doses 0.3 to 3 times the maximum recommended human dose. Based on data from animal reproduction studies, in utero exposure to benznidazole may cause fetal harm.
Congenital transmission of Chagas disease may occur, and the actual risk may depend on stage of maternal disease and geographic location (Bittencourt 1992). Transmission rates are increased during an acute infection, or in patients with HIV or who are immunocompromised (Rios 2020). There are no specific recommendations for preventing vertical transmission of disease in patients who are already pregnant (Carlier 2011).
T. cruzi infection during pregnancy may be associated with adverse maternal and fetal outcomes. However, information related to the use of benznidazole for the treatment of acute Chagas disease in pregnancy is limited (consult with specialist prior to treatment). Treatment of chronic disease during pregnancy is not recommended and should be postponed until after delivery (HHS [OI adult 2018]; Meymandi 2018).
Benznidazole is present in breast milk.
Information related to the presence of benznidazole in breast milk is available from 10 lactating women, 20 days to 13 months postpartum, administered benznidazole 5 to 8 mg/kg/day for 30 days. Breast milk concentrations of benznidazole correlated with maternal serum concentration and ranged from 0.3 to 5.9 mcg/mL. Using the highest milk concentration of 5.9 mcg/mL obtained from 1 woman 2 hours after the maternal dose (7 days after treatment started), authors of the study calculated the relative infant dose (RID) of benznidazole to be 17%, compared to a weight-adjusted maternal dose of 5.2 mg/kg/day (300 mg/day), providing an estimated daily infant dose via breast milk of 0.89 mg/kg/day. The RID of benznidazole ranged from 5.5% to 17% (median 12.3%). In 1 case, benznidazole remained present in breast milk 59.5 hours after the dose (0.3 mcg/mL). Three women withdrew from the study due to adverse events. Five infants were fully breastfed and 6 were partially breastfed. Adverse events were not observed in any infant (García-Bournissen 2015). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
Disease transmission may occur in patients with bleeding nipples (Bittencourt 1992). Maternal treatment for Chagas disease should be considered after breastfeeding has stopped (Carlier 2011). Due to the potential transmission of Chagas disease as well as the potential for serious adverse events in the breastfeeding infant, breastfeeding during benznidazole therapy is not recommended by the manufacturer.
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])
Inhibits the synthesis of DNA, RNA, and proteins within the T. cruzi parasite.
Absorption: Rapid (Bern 2007).
Distribution: Vd = 45 L.
Protein binding: ~44% to 60%.
Metabolism: Nitro reduction followed by glucuronidation.
Half-life elimination: ~13 hours.
Time to peak: Median: 2 hours.
Excretion: Urine (~68%) and feces (~21%).
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