Child-friendly dispersible formulations of many second-line TB medicines have been developed. These should be procured by NTPs and are strongly preferred for the treatment of young children with MDR/RR-TB over adult formulations, which must be manipulated (split, crushed, dissolved). Many of these are available through GDF, including bedaquiline 20 mg, delamanid 25 mg,20 levofloxacin 100 mg, moxifloxacin 100 mg, pyrazinamide 150 mg, ethambutol 100 mg, isoniazid 100 mg, ethionamide 125 mg and cycloserine 125 mg minicapsules. Practical instructions for their use have been developed by the Sentinel Project on Pediatric Drug-Resistant (122). A linezolid 150 mg dispersible tablet is being developed. For clofazimine, a 50 mg tablet formulation that can be dissolved in water in 2–5 minutes may be easier to administer to young children than the soft-gel capsule formulation.
The non-availability of child-friendly formulations should not be a barrier to treating children for MDR/RR-TB. Although not ideal, manipulated (split, crushed or dissolved) adult formulations can be used if other options are not available, especially when data exist about their bioequivalence. Bedaquiline adult tablets (100 mg) crushed and suspended in water have been shown to be bioequivalent to tablets swallowed whole and can be used to treat MDR/RR-TB in children if the dispersible tablet formulation of bedaquiline is unavailable or to facilitate administration in children who cannot swallow whole tablets (123). It is also possible to prepare sugar-containing and sugar-free extemporaneous liquid formulations of bedaquiline using the adult 100 mg formulation (Benefit Kids project, unpublished data)21.
For children and other people who cannot swallow whole tablets, a pharmacokinetic and bioavailability study has shown that the adult 50 mg tablet of delamanid can be dispersed in water with similar bioavailability as whole tablets (Benefit Kids project, unpublished data)22. It is possible to prepare sugarcontaining and sugar-free extemporaneous liquid formulations of delamanid using the adult 50 mg tablet (Benefit Kids project, unpublished data)23. Data on palatability are not available.
These bedaquiline and delamanid formulations use easily accessible ingredients and equipment and can be prepared in any pharmacy or dispensary. Detailed instructions for the preparation of these extemporaneous formulations are forthcoming.
20 A delamanid 25 mg dispersible tablet was not available at the time of the guideline development group meeting in May–June 2021, but it has since become available and is now listed in the GDF medicines catalogue (http://stoptb.org/assets/documents/gdf/drugsupply/
21 Taneja R, Nahata MC, Scarim J, et al. Stable sugar and sugar-free bedaquiline suspensions: practical implementation of pediatric dosing in the field. BENEFIT Kids Project, unpublished data.
22 Zou Y, Svensson E, Hesseling AC, et al. Relative Bioavailability of Delamanid 25mg, 50mg and 100mg, Administered to Healthy Adults under Fed Conditions Dispersed in Water Compared to Tablet Form: a Randomized Crossover Study. BENEFIT Kids Project,
23 Nahata MC, Scarim J, Scarim A, et al. Stable sugar and sugar-free liquid formulations of delamanid for use in patients with rifampicinresistant tuberculosis. BENEFIT Kids Project, unpublished data.