Therapeutic Uses

Nifurtimox and benznidazole are used to treat American trypanosomiasis (Chagas' disease) caused by T. cruzi. Because of toxicity, benznidazole is preferred. Both drugs markedly reduce the parasitemia, morbidity, and mortality of acute Chagas' disease, producing parasitological cures in 80% of cases. In the chronic disease, parasitological cures are still possible in up to 50% of patients. Even without a complete parasitological cure, treatment also reduces clinical symptoms. Treatment with nifurtimox or benznidazole has no effect on irreversible organ lesions. While part of tissue destruction may be autoimmune in nature, the continued presence of parasites in the infected organs of patients with chronic disease argues that Chagas'disease should be treated as a parasitic disease. The clinical response of the acute illness to drug therapy varies with geographical region. Treatment of all seropositive individuals is recommended and should be initiated as soon as possible. Therapy with nifurtimox or benznidazole should start promptly after exposure for persons at risk of T. cruzi infection from laboratory accidents or blood transfusions.

Both drugs are given orally. For nifurtimox, adults with acute infection should receive 8—10 mg/kg/day in four divided doses for 90—120 days. Children 1—10 years of age with acute Chagas' disease should receive 15—20 mg/kg/day in four divided doses for 90 days; for individuals 11-16 years old, the daily dose is 12.5—15 mg/kg given according to the same schedule. For benznidazole, the recommended treatment is 5—7 mg/kg/day in two divided doses for 30—90 days, with children up to 12 years receiving 10 mg/kg/day. Gastric upset and weight loss can occur during treatment. If the latter occurs, dosage should be reduced. The ingestion of alcohol should be avoided.

TOXICITY AND SIDE EFFECTS Drug-related side effects range from hypersensitivity reactions (e.g., dermatitis, fever, icterus, pulmonary infiltrates, and anaphylaxis) to dose- and age-dependent complications of the GI tract and the peripheral and CNS. Nausea and vomiting, myalgia, and weakness are common. Peripheral neuropathy and GI symptoms are especially common after prolonged treatment. Headache, psychiatric disturbances, paresthesias, polyneuritis, and CNS excitability are less frequent. Leukopenia and decreased sperm counts also have been reported. Because of the seriousness of Chagas' disease and the lack of superior drugs, there are few absolute contraindications to the use of these drugs.

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