Benznidazole-Related Adverse Drug Reactions and Their Relationship With Serum Drug Concentrations in Patients With Chronic Chagas Disease.

Health Biostatistics. Centre for International Health Research (CRESIB). Roselló, 132. 08036 Barcelona. Spain
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 10/2012; 57(1). DOI: 10.1128/AAC.01401-12
Source: PubMed


For treating Chagas disease (CD), currently a worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when theses drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole-ADRs and its relationship with serum concentrations in patients with chronic T. cruzi infection in order to perform a more accurate dosage to minimize ADRs.Fifty-four patients were recruited during 12 months. Fifty-three (98%) of the 54 patients had at least one ADR during follow-up, and the incidence of ADRs was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, seven among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days.Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up, and evaluated according clinical and epidemiological variables, and ADR severity. No relationship was found between benznidazole serum concentration and ADRs. The mean (standard deviation) trough serum benznidazole concentrations on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2) and 5.7 (1.7) mcg/mL, respectively. It is well known that trypanosomicidal concentration of benznidazole ranges from 3 to 6 mcg/mL, and data from our study reveals that using the established dose regime patients are overdosed.Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further well-controlled studies are necessary to establish optimal dose regimen for benznidazole in adults with chronic CD.

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Available from: Joaquim Gascón, Oct 03, 2014
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    • "Adults Benznidazole Adverse events 0.59 c 0.44–0.74 a Pinazo et al. (2013), Hasslocher-Moreno et al. (2012), Pinazo et al. (2010) Withdrawals 0.23 c 0.17–0.29 a Severe adverse events Nifurtimox Adverse events 0.975 0.73–1 Jackson et al. (2010) Withdrawals 0.395 0.3–0.5 a Severe adverse events 0.074 0.056–0.093 a Children Benznidazole Adverse events 0.58 0.44–0.73 "
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    • "Our data suggest that benznidazole, as well as nifurtimox and fexinidazole sulfone, are concentration-dependent trypanocidal drugs and therefore more efficacious at higher doses (above 100 μM, or 26 μg/mL, in the case of benznidazole). A recent study has determined the serum concentration of benznidazole in patients with chronic Chagas disease treated with 5 mg/kg/day for 60 days to range from 5 to 6.5 μg/mL on average67. This range is equivalent to 20–25 μM benznidazole, which was a suboptimal concentration (according to time-kill data in this study) against the Y strain for up to 96 h. "
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