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

Abstract

cFor treating Chagas disease (CD), a current 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 these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronic Trypanosoma cruzi infection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 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 to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) 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) g/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD.

Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

“…Only one individual was admitted to hospital, but this individual made a complete recovery and was later discharged. The higher rate of either neutropenia or hypertransaminasemia observed in our study might be explained by improved close monitoring of patients as has happened in other studies (15).…”

“…The published incidence of AEs varies from 40 to 50% up to 98% of patients (4,6,8,(12)(13)(14)(15)(16)(17). The data from our study are in the middle of the published ranges (76%).…”

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

“…It is important to consider this factor in clinical use, because even though the dose was doubled, the C max levels were close in comparison with the immediate-release adult tablet that is already on the market. According to literature data, plasma concentrations equal to or greater than 20 g/ml in humans increase the risk of adverse effects, mainly dermal manifestations (27).…”

Tripanosomiasis americana, una mirada desde el tratamiento

“…Algunos autores discuten la efectividad del tratamiento actualmente disponible, sugiriendo que dicha efectividad está determinada por diferentes facto-res como el estadio de la enfermedad, la dosis del medicamento, y la edad y procedencia geográfica del paciente que ha sido diagnosticado con esta parasitosis (9,21) . En la mayoría de los casos la detección de la enfermedad tiene lugar en las fases crónicas, cuando las secuelas ya mencionadas comienzan a ser más evidentes y el tratamiento antiparasitario parece no ser tan efectivo (14,22) .…”