The Expert Committee did not recommend the requested change to the age
restriction that applies to the listing of delamanid on the Model Lists. The
Committee noted that pharmacokinetic data used to inform the guideline
development process used a different formulation of delamanid to that currently
included on the Model Lists, which is not commercially available at this time, nor
has it been demonstrated to be bioequivalent to the available, listed formulation.
The application requested a change to the age restriction that applies to the listing
of delamanid on the Model Lists.
In 2017, delamanid was added to the EMLc as a reserve second-line drug for
multidrug-resistant tuberculosis (MDR-TB) in children aged 6–17 years. The
current Model Lists include an age limit for delamanid of >6 years.
As part of the MDR-TB guideline development process, paediatric data
for delamanid were reviewed to examine whether the recommendations for
delamanid use in children could be lowered to children under 6 years of age.
Safety and pharmacologic exposure data were available from ongoing paediatric
studies (1). The WHO Guideline Development Group (GDG) concluded that
based on the pharmacokinetic data, exposure profiles in children aged 3 to
5 years were comparable to adults and no higher than in children aged 6 and
older. From the available data, there were no safety signals distinct from those
reported in adults observed in children aged three to five years. The GDG
concluded that extrapolations of efficacy and safety should be restricted to
children 3 years of age and older.
Children aged 3 to 5 years in the trials were administered delamanid at a dose of
25 mg twice daily, using a scored, dispersible paediatric formulation that is not
The only source of delamanid is the 50 mg adult formulation which
poses potential problems when considered for children under 6 years of age.
The adult and paediatric formulations of delamanid are not bioequivalent
or interchangeable. Equal doses of each formulation achieve different
concentrations in the body. Substituting the adult formulation for the paediatric
formulation will result in higher delamanid exposures than would be expected
from the paediatric formulation.
In addition, splitting or crushing of the adult tablet for administration
to children will affect the stability of the medicine and result in pill fragments
that are exceedingly bitter.
The 2019 WHO consolidated guidelines on drug-resistant tuberculosis treatment
(2) make the following recommendation with regard to delamanid: “Delamanid
may be included in the treatment of MDR-TB/RR-TB patients aged 3 years or
more on longer regimens (conditional recommendation, moderate certainty in
the estimates of effect.”
Delamanid 50 mg tablets are manufactured by Otsuka Pharmaceutical, Japan.
They are available to eligible countries through the Global Drug Facility. The
25 mg paediatric dispersible tablet formulation is not currently commercially
1. WHO consolidated guidelines on drug-resistant tuberculosis treatment (Annexes 3–9). Geneva:
World Health Organization; 2019. Available from https://apps.who.int/iris/bitstream/handle/
10665/311390/WHO-CDS-TB-2019.3-eng.pdf, accessed 30 October 2019.
2. 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.