The Expert Committee recommended the addition of the proposed dispersible
tablet formulations of ethambutol and isoniazid to the core list of the EMLc,
and of cycloserine, ethionamide, levofloxacin, linezolid and moxifloxacin to the
complementary list of the EMLc for the treatment of children with drug-sensitive
and drug-resistant TB.
The Committee considered that the availability of quality-assured, age-appropriate
formulations will help improve access to effective treatment for
children with TB.
The application requested the addition of various new formulations of currently listed
medicines for tuberculosis (TB) for use in children, including cycloserine 125 mg solid oral dose form.
Public health relevance
It is estimated that of the 10 million people who developed TB in 2017, 1 million
of them were children. Children aged <15 years accounted for 7.1% of the 6.4
million new or relapsed cases of TB notified to national TB programmes and
reported to WHO. Children aged <15 years accounted for 15% and 10% of total
TB deaths among HIV-negative and HIV-positive people, respectively – higher
than their share of estimated cases, suggesting poorer access to diagnosis and
Evidence for the clinical effectiveness of the medicines was evaluated at the time
of their individual listings.
The proposed new formulations are mostly dispersible formulations, meaning
they can be mixed in liquid, making it easier to get the correct doses and for
children to swallow. They are flavoured to overcome the bitterness associated
with breaking, crushing and otherwise manipulating adult formulations.
The proposed formulations are at lower strengths, aligned with the
dosing needs of children according to the 2019 update of the WHO consolidated
guidelines on drug-resistant tuberculosis treatment (4). With the exception of
linezolid 150 mg dispersible tablet (which is still in development), the proposed
formulations are all quality-assured, either through the WHO Prequalification
for Medicines Programme, or by the Global Fund Expert Review Panel.
Evidence for the safety of the medicines was evaluated at the time of their
Cost / cost effectiveness
No information was provided in the application.
These medicines are all recommended the most recent WHO guidelines for
treatment of drug-sensitive tuberculosis (2017) (5), treatment of latent TB
infection (2018) (6), treatment of isoniazid mono-resistant TB (2018) (7) and
treatment of drug-resistant TB (2019) (4).
The proposed new formulations are in the Stop TB Partnership’s Global Drug
Facility product catalogue and are reportedly being procured by programmes.
Comments on the application were received from the WHO Global TB
Programme. The technical unit advised that it supported the application, which
was developed in consultation with the Global TB Programme, and was fully in
line with the latest WHO recommendations on the management of multidrug-resistant
TB (MDR-TB), rifampicin-resistant TB (RR-TB) and isoniazid-resistant
TB. The technical unit stated that the addition of child-friendly formulations of
second-line antituberculosis medicines will greatly benefit children with drug-resistant
1. Guidelines for the programmatic management of drug-resistant tuberculosis - 2011 update. Geneva: World Health Organization; 2011.
2. Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, Bayona JN, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med. 2012;9(8):e1001300.
3. Hwang TJ, Wares DF, Jafarov A, Jakubowiak W, Nunn P, Keshavjee S. Safety of cycloserine and terizidone for the treatment of drug-resistant tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2013;17(10):1257-66.