BENZNIDAZOLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENZNIDAZOLE (BENZNIDAZOLE).
Benznidazole is a nitroimidazole derivative that exerts trypanocidal activity against Trypanosoma cruzi. Its mechanism involves the reduction of the nitro group by a nitroreductase enzyme in the parasite, leading to the generation of toxic metabolites that damage parasite DNA and other cellular components.
| Metabolism | Hepatic metabolism primarily via cytochrome P450 enzymes, including CYP2D6, CYP3A4, and CYP2C19. |
| Excretion | Primarily renal excretion of metabolites; <5% unchanged drug. Approximately 20% in feces. |
| Half-life | Terminal elimination half-life is approximately 12 hours; may be prolonged in hepatic impairment. |
| Protein binding | Approximately 30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd approximately 0.6 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: approximately 92% absorbed; high bioavailability. |
| Onset of Action | Oral: clinical effect (parasitemia reduction) observed within 24-48 hours. |
| Duration of Action | Duration of action corresponds to treatment course (typically 60 days); no prolonged effect after discontinuation. |
5-7 mg/kg/day orally divided into two daily doses for 60 days. Maximum daily dose: 300 mg.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines available; use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | No specific dose adjustment guidelines; contraindicated in Child-Pugh class C due to risk of hepatotoxicity. |
| Pediatric use | 5-10 mg/kg/day orally divided into two daily doses for 60 days; maximum daily dose 300 mg. Weight-based dosing: 5-7.5 mg/kg/day for children ≤40 kg. |
| Geriatric use | No specific adjustment; use standard adult dose with close monitoring for adverse effects due to potential age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BENZNIDAZOLE (BENZNIDAZOLE).
| Breastfeeding | Breastfeeding is not recommended during benznidazole therapy. The M/P ratio is unknown; however, the drug is excreted into breast milk in animal models and may cause adverse effects in the nursing infant. |
| Teratogenic Risk | Benznidazole is contraindicated in the first trimester due to potential embryotoxicity and teratogenicity observed in animal studies. In second and third trimesters, use only if benefit outweighs risk, with caution due to possible fetal harm (limited human data available). |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to benznidazole or any component of the formulation","Severe hepatic or renal impairment","Pregnancy (Category C; should not be used unless unavoidable)","Lactation (discontinue breastfeeding or drug)"]
| Precautions | ["Bone marrow suppression (leukopenia, neutropenia, agranulocytosis, thrombocytopenia); monitor blood counts","Peripheral neuropathy (dose-dependent, may be irreversible)","Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)","Hepatotoxicity (elevated liver enzymes, hepatitis)","Hypersensitivity reactions (allergic dermatitis, fever)","Fetal harm (avoid in pregnancy unless benefit outweighs risk)"] |
| Food/Dietary | Avoid alcohol and alcohol-containing products during treatment and for 3 days after discontinuation due to risk of disulfiram-like reaction. No specific food restrictions; taking with a meal or snack can reduce nausea and vomiting. |
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| Monitor complete blood counts (CBC) and liver function tests (LFTs) monthly due to risks of bone marrow suppression and hepatotoxicity. Assess fetal growth and well-being with ultrasound if used in pregnancy. Observe for signs of peripheral neuropathy in the mother. |
| Fertility Effects | Benznidazole may impair fertility based on animal studies showing reduced spermatogenesis and estrous cycle alterations. Human data are lacking; potential for reversible effects on fertility should be considered. |
| Clinical Pearls | Monitor for peripheral neuropathy (paresthesias, dysesthesia) which may be irreversible if not caught early. Obtain baseline and periodic EKGs due to risk of QT prolongation. Avoid use in pregnant women or those planning pregnancy; effective contraception is required during therapy and for 3 months after last dose. Dose adjustments not needed in mild to moderate hepatic impairment, but avoid in severe impairment. Administer with food to reduce gastrointestinal upset. |
| Patient Advice | Take with food to minimize stomach upset. · Complete the full course of treatment even if you feel better. · Avoid alcohol during treatment and for 3 days after stopping, as it may cause a disulfiram-like reaction (nausea, vomiting, headache). · Report any numbness, tingling, or unusual skin sensations to your doctor immediately. · Use reliable contraception during treatment and for 3 months after the last dose. · Do not drive or operate heavy machinery if you experience dizziness or drowsiness. · Inform your doctor if you have a history of heart problems, seizures, or kidney disease. |