Adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children

Abstract

Purpose: Many children with urological disease require long-term treatment with antibiotics. In many cases the choice of medical instead of surgical management hinges on the implied safety of certain drugs. Recently some groups have advocated subureteral injection procedures to avoid long-term antibiotics for low grade reflux. We present a concise and relevant review on the use and adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children.

Materials and methods: We reviewed the literature regarding the safety and toxicity of these drugs. Information regarding absorption, excretion and dosing was also gathered to explain better the mechanisms of toxicity.

Results: Adverse reactions in children reported in the literature related to nitrofurantoin are gastrointestinal disturbance (4.4/100 person-years at risk), cutaneous reactions (2% to 3%), pulmonary toxicity (9 patients), hepatoxicity (12 patients and 3 deaths), hematological toxicity (12 patients), neurotoxicity and an increased rate of sister chromatid exchanges. Adverse reactions in children related to trimethoprim/sulfamethoxazole are almost exclusively due to the sulfamethoxazole component, including cutaneous reactions (1.4 to 7.4 events per 100 person-years at risk), hematological toxicity (0% to 72% of patients) and hepatotoxicity (5 patients). The majority of adverse reactions were found in children on full dose therapy and not prophylaxis.

Conclusions: The use of nitrofurantoin, trimethoprim and sulfamethoxazole is safe in children for long-term prophylactic therapy. The antibiotic safety issue should not be misconstrued as an argument for surgical therapy, whether minimally invasive or not. Adverse reactions exist to these medicines but they are less common than seen in adults, presumably because of the lower dose used for therapy, and the lack of significant comorbidities and drug interactions in children. Serious side effects are extremely rare and most are reversible by discontinuing therapy. The extremely low potential for significant adverse reactions should be discussed with parents.