Article

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: 4.45). 10/2012; 57(1). DOI: 10.1128/AAC.01401-12
Source: PubMed

ABSTRACT 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.

Full-text

Available from: Joaquim Gascón, Oct 03, 2014
0 Followers
 · 
97 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The anti-chagasic activity of a series of eleven derivatives of aza-scorpiand-like macrocycles, some of them newly synthesised, was assayed. The four compounds with the best selectivity indices in vitro were subjected to in vivo assays. Tests in a murine model of the acute phase of Chagas disease showed a two-fold reduction in parasitaemia compared to that with benznidazole. Furthermore, compounds 7 and 11, with 4-pyridine and phenanthroline substituents in the lateral chain, caused a remarkable decrease in parasitaemia reactivation during the chronic phase after inducing immunosuppression in mice. These activity studies were complemented by measuring their inhibitory effect towards the antioxidant parasite-specific enzymes Fe-superoxide dismutase (Fe-SOD) and trypanothione reductase (TR), the metabolites excreted after treatment and ultrastructural alterations. The ability of selected macrocycles to complex with Fe(II) and Fe(III) was studied by potentiometric methods. Detailed molecular dynamics studies provided interesting hints about the way in which the compounds approach and modify the active centre of Fe-SOD. The activity, low toxicity, stability, low cost of the starting materials and straightforward synthesis make these compounds appropriate molecules for the development of affordable anti-chagasic agents.
    RSC Advances 11/2014; 4(110). DOI:10.1039/C4RA09866H · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: 1) non-screening; 2) screening of the Latin American pregnant women and their newborns; 3) screening also the relatives of the positive pregnant women; 4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative mothers. Copyright © 2015. Published by Elsevier B.V.
    Acta tropica 04/2015; 148. DOI:10.1016/j.actatropica.2015.04.014 · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chagas disease is a parasitic infection that leads to a significant public health problem in both endemic and non-endemic countries. Benznidazole is the most commonly used drug for the etiological treatment. Patients treated with benznidazole suffer frequent adverse drug reactions and whereas arthromyalgia is common, arthritis is reported as a very rare side effect. The objective of this study is to describe arthritis in a cohort of Trypanosoma cruzi infected patients treated with benznidazole.
    Antimicrobial Agents and Chemotherapy 11/2014; 59(1). DOI:10.1128/AAC.04078-14 · 4.45 Impact Factor