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 moxifloxacin dispersible tablet 100 mg.
All of the medicines for which additional formulations are requested for listing
are currently included on the Model Lists in various formulations and strengths.
In 2007, the World Health Assembly called for WHO to promote the
development of child-friendly medicines with a particular focus on treatment
for HIV, tuberculosis, malaria and chronic disease (1).
In 2017, the Expert Committee recommended the addition to the EMLc
of two fixed-dose combination, child-friendly dispersible tablet formulations of
isoniazid + rifampicin +/– pyrazinamide for use in children with drug-sensitive
tuberculosis infection. The Committee considered that the availability of these
age-appropriate formulations would offer benefits including appropriate dosing,
ease of administration and reduced pill burden (2).
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. Resolution WHA60.20. Better medicines for children. In: Sixtieth World Health Assembly,
Geneva, 14–23 May 2007. Resolutions and decisions. Geneva: World Health Organization; 2007.
Available from: http://apps.who.int/gb/ebwha/pdf_files/WHASSA_WHA60-Rec1/E/reso-60-en.
pdf, accessed 30 October 2019.
2. The selection and use of essential medicines. Report of the WHO Expert Committee, 2017
(including the 20th WHO Model List of Essential Medicines and the 6th WHO Model List of
Essential Medicines for Children) (WHO Technical Report Series, No. 1006). Geneva: World
Health Organization; 2017. Available from https://apps.who.int/iris/bitstream/handle/10665/
259481/9789241210157-eng.pdf, accessed 30 October 2019.
3. Global tuberculosis report 2018. Geneva: World Health Organization; 2018. Available from
30 October 2019.
4. WHO consolidated guidelines on drug-resistant tuberculosis treatment. Geneva: World
Health Organization; 2019. Available from: https://apps.who.int/iris/bitstream/handle/10665/
311389/9789241550529-eng.pdf, accessed 30 October 2019.
5. Guidelines for treatment of drug-susceptible tuberculosis and patient care, 2017 update.
Geneva: World Health Organization; 2017. Available from: https://apps.who.int/iris/bitstream/
handle/10665/255052/9789241550000-eng.pdf, accessed 30 October 2019).
6. Latent tuberculosis infection: Updated and consolidated guidelines for programmatic
management. Geneva: World Health Organization; 2018. Available from https://www.who.int/
tb/publications/2018/latent-tuberculosis-infection/en/, accessed 30 October 2019.
7. WHO treatment guidelines for isoniazid-resistant tuberculosis: Supplement to the WHO
treatment guidelines for drug-resistant tuberculosis. Geneva: World Health Organization; 2018.
Available from: https://apps.who.int/iris/bitstream/handle/10665/260494/9789241550079-eng.
pdf, accessed 30 October 2019.