Essential medicines for children

Tuberculosis treatment in children

Access to appropriate treatment for childhood tuberculosis remains a challenge. Treatment guidelines have been updated to reflect evidence on appropriate dosing and their implementation should lead to improved clinical outcomes. Fixed-dose combinations are generally the accepted solution for treating children. However, fixed-dose combination products available on the market do not correspond to the appropriate doses, making correct treatment complicated or impossible. Progress on developing appropriate fixed-dose combination products for children has been slow.

Treatment guidelines

The dosing recommendations are based on considerations of drug-induced hepatotoxicity and the finding that previous dosing regimens do not provide adequate therapeutic levels in children. The new recommendations are based on robust scientific evidence and are consistent with other published guidelines.

Recommendation at a glance for first line treatment:

  • Isoniazid: 10 mg/kg/day (10–15 mg/kg/day)
  • Rifampicin: 15 mg/kg/day (10–20 mg/kg/day)
  • Pyrazinamide: 35 mg/kg/day (30–40 mg/kg/day)
  • Ethambutol: 20 mg/kg/day (15–25 mg/kg/day)

Dosing instructions for the use of currently available anti-tuberculosis medicines

A number of fixed-dose combination products have been approved by the UN prequalification programme and several others are available on the market. However, none of these alone are ideal for children. Dosing charts have been constructed as a guide to achieve the desirable doses of medicines for children using the currently available products until the appropriate fixed-dose combination products are available.

WHO List of Essential Medicines for Children

The current List includes only single component products for the treatment of tuberculosis in children. This is to ensure that selection committees, procurement agencies and reimbursement committees are guided to select appropriate products that are commercially available. However, as long as the relevant fixed-dose combination products are not listed on the List, it will be difficult to implement the recommended treatment regime.

Development of an appropriate fixed-dose combination

While an ideal fixed-dose combination would combine 3 or 4 of the medicines rifampicin, ethambutol, isoniazid and pyrazinamide, there are challenges in developing an actual product. Large tablet size, interactions between drug components and excipient, and bioavailability issues contribute to the complexity of developing an appropriate fixed-dose combination. Collaboration between all stakeholders including international organizations, academia, industry, regulators, and practitioners is needed to facilitate the development of an appropriate product.

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Contact: pedmeds@who.int

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