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Drug Safety

pp 1–14 | Cite as

Safety Profile of Benznidazole in the Treatment of Chronic Chagas Disease: Experience of a Referral Centre and Systematic Literature Review with Meta-Analysis

  • Clara Crespillo-Andújar
  • Emmanuele Venanzi-Rullo
  • Rogelio López-Vélez
  • Begoña Monge-Maillo
  • Francesca Norman
  • Ana López-Polín
  • José A. Pérez-Molina
Systematic Review

Abstract

Introduction

Benznidazole is the preferred drug for treatment of Chagas disease. However, it is toxic and of limited value in chronic infection.

Objective

We aimed to estimate the rates of and factors related to adverse reactions (ARs) to benznidazole and treatment discontinuations (TDs).

Methods

A meta-analysis was performed using an electronic search of the published literature with no language restrictions until June 2017. Prospective studies were included of chronically infected patients in which at least one treatment arm included benznidazole. Data were added from a prospective cohort of patients with Chagas disease at our centre (January 2007–June 2017). Weighted rates of ARs and TDs were estimated, and potentially related factors were analysed.

Results

Some 413 studies were found, from which we chose 42 (nine clinical trials and 33 observational studies, including ours), comprising data for 7822 patients. The weighted rate of ARs to benznidazole was 44.1% (95% confidence interval [CI] 37.2–51.2). ARs were more frequent in adults than in children (51.6 vs. 24.5%), with the most common being skin reactions (34%), gastrointestinal complaints (12.6%) and neurological symptoms (11.5%). Grade 4 ARs were recorded in 3% of cases. The weighted rate of TDs was 11.4% (95% CI 8.5–14.5); TDs were more frequent in adults than in children (14.2 vs. 3.8%). In our cohort, only female sex was related to an increased rate of ARs but not to TDs.

Conclusion

Benznidazole had a poor tolerability profile, with a high incidence of TDs, especially in adult patients and women. Optimised dosing schedules and/or new drugs are urgently needed.

Notes

Compliance with Ethical Standards

Funding

Funding was provided by ISCIII (Instituto de Salud Carlos III), project “RD16/0027/0020 and RD16/0027/0002” Red de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I + D + I 2013–2016 and by FEDER (Fondo Europeo de Desarrollo Regional).

Conflict of interest

Clara Crespillo-Andújar, Emmanuele Venanzi-Rullo, Rogelio López-Vélez, Begoña Monge-Maillo, Francesca Norman, Ana López-Polín and José A. Pérez-Molina declare that they have no conflict of interest.

Supplementary material

40264_2018_696_MOESM1_ESM.docx (84 kb)
Supplementary material 1 (DOCX 83 kb)

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Clara Crespillo-Andújar
    • 1
  • Emmanuele Venanzi-Rullo
    • 2
  • Rogelio López-Vélez
    • 3
  • Begoña Monge-Maillo
    • 3
  • Francesca Norman
    • 3
  • Ana López-Polín
    • 3
  • José A. Pérez-Molina
    • 3
  1. 1.National Referral Unit for Tropical and Travel Medicine, Department of Internal MedicineHospital Universitario La Paz-Carlos III, IdiPAZMadridSpain
  2. 2.Division of Infectious DiseasesUniversity of Messina, Polyclinic “G. Martino”MessinaItaly
  3. 3.National Referral Centre for Tropical Diseases, Infectious Diseases DepartmentHospital Universitario Ramón y Cajal, IRYCISMadridSpain

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