Is ethambutol (antitubercular agent) safe to use in small children with tuberculosis (TB)?

Ethambutol Safety in Small Children with Tuberculosis

Ethambutol can be safely used in small children with tuberculosis, including those under 5 years of age, when there is concern about drug resistance, though it should be used with caution in children whose visual acuity cannot be monitored. 1

Safety Profile and Recommendations

• Ethambutol (EMB) is a first-line drug for treating all forms of tuberculosis and is included in initial treatment regimens primarily to prevent emergence of rifampicin resistance when primary isoniazid resistance may be present 1
• While the FDA label states that EMB is not recommended for children under 13 years of age 2, more recent evidence and guidelines support its use in younger children
• The British Thoracic Society guidelines state that ethambutol can be used in younger children without undue fear of side effects 1
• For children aged five years or more, ethambutol can be recommended at a dosage of 15 mg/kg/day without taking any more precautions than for adults 1

Dosing Recommendations

• For children: 15-20 mg/kg/day (maximum 2.5g); or 50 mg/kg twice weekly (maximum 2.5g) 1
• Some studies suggest calculating EMB dosage based on body surface area (867 mg/m²) rather than body weight to achieve therapeutic serum levels in all age groups, especially in younger children 3
• EMB serum levels are significantly lower in children receiving the same weight-based dosage as adults, which may require dosage adjustments 4, 5

Ocular Toxicity Concerns

• The primary concern with EMB use is retrobulbar neuritis, which can manifest as decreased visual acuity or decreased red-green color discrimination 1
• The risk of ocular toxicity is dose-related, with minimal risk at a daily dose of 15 mg/kg 1
• In a review of 3,811 children receiving EMB doses of 15-30 mg/kg, only 2 cases (0.05%) required discontinuation due to possible ocular toxicity 4
• Another study found ocular toxicity in only 0.7% of children treated with EMB dosed by body surface area 3
• A study using visual evoked responses (VERs) in children aged 3-13 years receiving EMB at 20 mg/kg/day found no statistically significant changes in visual function, suggesting children are not at greater risk for developing EMB-induced optic damage compared to adults 6

Monitoring Recommendations

• Baseline visual acuity testing should be performed when possible before starting EMB 1
• For children old enough to cooperate, visual acuity should be tested by Snellen chart before EMB is prescribed 1
• Parents or caregivers should be informed about potential visual symptoms and instructed to stop the medication immediately if such symptoms occur 1
• For children with TB meningitis who are unconscious (stage III), EMB should be used with caution as visual acuity cannot be tested 1
• If any deterioration in visual fields or color vision is detected, strong consideration should be given to stopping or switching the EMB 1

Special Situations

• In TB meningitis, EMB can be used as the fourth drug in the initial treatment phase, along with rifampicin, isoniazid, and pyrazinamide 1
• For children with HIV on lopinavir/ritonavir, bioavailability of EMB is reduced by 32%, which may require dosage adjustments 5
• EMB should be included in the initial regimen until drug susceptibility results are available, unless there is little possibility of drug resistance 7

Conclusion

Despite historical concerns and FDA labeling restrictions, current evidence supports the safe use of ethambutol in children of all ages when clinically indicated, particularly when drug resistance is a concern. Appropriate monitoring and dosing are essential to minimize the risk of ocular toxicity.