Clara Crespillo-Andújar1, Emmanuele Venanzi-Rullo2, Rogelio López-Vélez3, Begoña Monge-Maillo3, Francesca Norman3, Ana López-Polín3, José A Pérez-Molina4. 1. National Referral Unit for Tropical and Travel Medicine, Department of Internal Medicine, Hospital Universitario La Paz-Carlos III, IdiPAZ, Madrid, Spain. 2. Division of Infectious Diseases, University of Messina, Polyclinic "G. Martino", Messina, Italy. 3. National Referral Centre for Tropical Diseases, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Km 9, 1, 28034, Madrid, Spain. 4. National Referral Centre for Tropical Diseases, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Km 9, 1, 28034, Madrid, Spain. jperezm@salud.madrid.org.
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.
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.
Authors: A Riarte; C Luna; R Sabatiello; A Sinagra; R Schiavelli; A De Rissio; E Maiolo; M M Garcìa; N Jacob; M Pattin; M Lauricella; E L Segura; M Vázquez Journal: Clin Infect Dis Date: 1999-09 Impact factor: 9.079
Authors: I Molina; F Salvador; A Sánchez-Montalvá; M A Artaza; R Moreno; L Perin; A Esquisabel; L Pinto; J L Pedraz Journal: Antimicrob Agents Chemother Date: 2017-03-24 Impact factor: 5.191
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Authors: Cristina Alonso-Vega; Julio A Urbina; Sergi Sanz; María-Jesús Pinazo; Jimy José Pinto; Virginia R Gonzalez; Gimena Rojas; Lourdes Ortiz; Wilson Garcia; Daniel Lozano; Dolors Soy; Rosa A Maldonado; Rana Nagarkatti; Alain Debrabant; Alejandro Schijman; M Carmen Thomas; Manuel Carlos López; Katja Michael; Isabela Ribeiro; Joaquim Gascon; Faustino Torrico; Igor C Almeida Journal: BMJ Open Date: 2021-12-31 Impact factor: 2.692