Does Progressive Introduction of Benznidazole Reduce the Chance of Adverse Events in the Treatment of Chagas Disease?

Abstract

In this retrospective cohort study, we aimed to assess whether introducing benznidazole at escalating doses reduces the probability of adverse events or treatment discontinuation compared with a full-dose scheme. We collected data from patients who had chronic Trypanosoma cruzi infection and underwent treatment from July 2008 to January 2017 in a referral center in Madrid. Dose was adjusted to body weight (5 mg/kg/day), with treatment introduction with full dose or escalating dose according to local consensus and protocols. Among the 62 patients treated, benznidazole was introduced at full dose in 28 patients and on escalating dose in the remaining 34. We found no statistical differences in the number of adverse events, treatment discontinuations, days of treatment, or sociodemographic profiles. There is insufficient evidence to support escalating dose as a strategy for reducing the adverse effects of benznidazole. Further research is needed to evaluate this approach.

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres

“…The frequency of AR, the type of AR and time to first AR were similar between both treatment groups, with the only exception being musculoskeletal reactions. Similarly, a recently published retrospective cohort study (n ¼ 62) found that the use of increasing doses of benznidazole showed no benefits in terms of incidence or type of adverse reactions or a reduction in the treatment discontinuation rates [10].…”

A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease

“…We included three RCTs [ 20 , 21 , 22 ] and 10 observational studies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. The studies were conducted in Latin American countries or in non-endemic countries with Latin American immigrants ( Table 1 ).…”

“…Of the 13 studies included, 11 reported the dosage of BNZ used [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 30 , 31 ], while the remaining two only reported “treated or untreated” based on participant response [ 29 , 32 ]. The most commonly used dosage of BNZ was 5 mg/kg/day orally for 60 days, with two studies using escalating doses (titration), starting at 50 mg on day one and increasing by 50 mg daily until reaching a 300 mg daily dose or in accordance with the participant’s weight ( Table 1 ) .…”

“…The trypanocidal drugs used in the included studies were BNZ, NFX, POS and E1224 (a water-soluble Ravuconazole); three studies [ 25 , 28 , 30 ] compared variations in BNZ dosing. Except for one study that initiated with acute patients, all studies participants were at some stage of indeterminate or chronic Chagas disease.…”

“…The studies reported varying frequency of AEs according to the trypanocidal used. Of the 13 studies, seven presented a thorough reporting [ 20 , 21 , 22 , 23 , 28 , 29 , 30 ], two had incomplete reporting [ 24 , 25 ], and four did not report any AEs [ 26 , 27 , 31 , 32 ]. Three studies did not report AEs because it was not an outcome of interest, and one because AEs were reported in the original study conducted by Morillo et al, 2015 [ 20 ], which is also included in this review.…”