Adverse Events Associated with Nifurtimox Treatment for Chagas Disease in Children and Adults

Abstract

BACKGROUND: Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, there is scarce data on NF safety, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. METHODS: Retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD. Children received NF doses of 10-15 mg/kg/day for 60-90 days, and adults 8-10 mg/kg/day for 30 days. Results: 215 children (median age: 2.6yrs, range 0-17) and 105 adults (median age: 34yrs, range 18-57) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 in adults, and 63/215 in children (OR = 3.7, 95%CI [2.2;6.3]). We observed 215 ADRs, 131 in adults (median: 2 events/patient (IQR25-75= 1-3) and 84 in children (median: 1 event/patient (IQR25-75= 1-1.5) (PAdjusted < 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous and digestive systems were the most frequently affected, without differences between both groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95%CI = [1.5;24]). CONCLUSIONS: Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence.

Characteristics and Adverse Events of Patients for Whom Nifurtimox Was Released Through CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease — United States, 2001–2021

“…However, FDA-approved drugs can be used for nonapproved indications (i.e., off-label use), in accordance with the practice of medicine. The frequency of adverse events in adults and the most common adverse events and systems affected in children, adolescents, and adults were consistent with those reported in previous studies ( 3 – 7 ). The clinical study cited in the FDA approval of nifurtimox (Lampit) did not include adults but found that adverse events were more frequent in adolescents (aged 12 to <18 years) compared with younger age groups ( 8 ).…”

“…Children and adolescents treated under the CDC IND were older (median age = 17 years) and reported more adverse events than in that study (90% versus 64.5%) ( 8 ). Among all age groups, the percentage of severe adverse events was higher than that described in other reports (10.4% versus 3.2%–5.1%) ( 5 , 6 ), including among children (13.3% versus 0.9%–1.6%) ( 3 , 8 ). These differences might be because of the way in which adverse events were reported, treatment dose differences, and older ages of children treated with nifurtimox under CDC’s protocol.…”

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

“…Treatment discontinuation with NFX was only reported in two studies, which were 10.7% and 0%, respectively. Other studies have reported treatment discontinuation with NFX at 20% [ 34 ], 9.9% [ 35 ], and 9.7% [ 36 ].…”

Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults

“…There have been some concerns about the safety of NF. In a previous study, we demonstrated that NF is a safe option for ChD treatment ( 4 ). In this study, we systematically assessed the effectiveness of NF considering the same ChD cohort population, which included both children and adult patients with a long-term follow-up of more than 10 years.…”