Target product profiles for paediatric formulations of azithromycin and nitrofurantoin.
Nisar YB., Brigadoi G., Ariff S., Arora NK., Bekker A., Berkley JA., Bielicki JA., Cressey TR., Dixit D., Frigati L., Gwee A., Karim M., Kshirsagar R., Mujuru HA., Musiime V., Ojoo M., Ranganathan SS., Roilides E., Sharland M., Tuleu C., Wammanda RD., Williams P., Penazzato M.
Bacterial infections are still a main cause of death in children younger than 5 years, yet few age-appropriate antibiotic formulations exist, which limits treatment options and compromises quality of care. In 2023, the World Health Organization (WHO) published its first list of priority paediatric antibiotic formulations to guide research and development for age-appropriate antibiotic formulations. Both azithromycin and nitrofurantoin are on this list. Currently, no dispersible tablets are approved or available for these drugs and existing liquid forms are poorly palatable and/or contain excipients of safety concern. To support the development of age-appropriate formulations for these two antibiotics, we produced target product profiles using WHO's methods. For azithromycin, the optimum age-appropriate formulation and dose is scored 100 mg dispersible tablets or an orodispersible 50 mg multiparticulate formulation, with dispersible 50 mg tablets as the minimum requirement. For nitrofurantoin, the optimum age-appropriate formulation is an orodispersible multiparticulate formulation or scored dispersible tablets, with dispersible tablets as the minimum requirement. Based on the WHO recommended dosage of 4 mg/kg per day for children for nitrofurantoin, the optimum unit dose is 5 mg. If scoring is feasible, a 10 mg unit dose should be developed for dosing flexibility across paediatric age groups. These profiles aim to support regulatory authorities, pharmaceutical developers, health programmes and other stakeholders in advancing safer, effective and child-appropriate antibiotic formulations.