Ethambutol dosage for the treatment of children: literature review and recommendations

Abstract

The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/ kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/ kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern.