s 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 reactions: rash, leukopenia, urticaria, eosinophilia, decreased appetite, and neutropenia. These adverse reactions were similar to those observed in the overall population of 37 patients.
6.2 Post-marketing Experience
The following adverse reactions have been identified during the use of other formulations of benznidazole outside of the United States. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Table 5: Adverse Reactions Reported in the Published Literature
Body System
Adverse Reactions
Dermatological
•Maculo-papular cutaneous eruptions
•Erythematous plaques
•Rash, generalized
•Rash, erythematous
•Pruritic rash
•Blistering eruptions
•Peeling skin
•Exfoliative dermatitis
•Toxic epidermal necrolysis
•AGEP
•Erythema multiforme
•Drug reaction with eosinophilia and systemic symptoms
Neurological (central and peripheral nervous system)
•Paresthesia
•Hypoesthesia
•Headaches
•Insomnia
•Convulsions
•Inability to concentrate
•Amnesia, temporary
•Disorientation, temporary
Gastrointestinal
•Epigastric pain
•Dry mouth
•Ageusia
Hepatobiliary disorders
•Hepatitis
•Toxic
