ATC codes: J04AK06
Multi-drug resistant tuberculous Mycobacterium ICD11 code: ML32.00
Medicine type
Chemical agent
List type
Complementary Medicines for the treatment of multidrug-resistant tuberculosis (MDR-TB) should be used in specialized centres adhering to WHO standards for TB contol.
Oral > Solid: 50 mg tablet
EML status history
First added in 2015 (TRS 994)
Changed in 2017 (TRS 1006)
Changed in 2019 (TRS 1021)
Also recommended for children
Age restriction
≥6 years
Therapeutic equivalence
The recommendation is for this specific medicine
Patent information
Main patent is active in several jurisdictions. For more information on specific patents and license status for developing countries visit www.MedsPal.org
Expert Committee recommendation
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.
Additional evidence
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 currently available. 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.
WHO guidelines
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 available.
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.