Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children

Abstract

Infants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available. Artemisinin-based combination therapy is the current standard of care for patients with uncomplicated falciparum malaria in Africa. Artemether/lumefantrine (AL) meets WHO pre-qualification criteria for efficacy, safety and quality. Coartem, a fixed dose combination of artemether and lumefantrine, has consistently achieved cure rates of >95% in clinical trials. However, AL tablets are inconvenient for caregivers to administer as they need to be crushed and mixed with water or food for infants and young children. Further, in common with other anti-malarials, they have a bitter taste, which may result in children spitting the medicine out and not receiving the full therapeutic dose. There was a clear unmet medical need for a formulation of AL specifically designed for children. Ahead of a call from WHO for child-friendly medicines, Novartis, working in partnership with Medicines for Malaria Venture (MMV), started the development of a new formulation of AL for infants and young children: Coartem Dispersible. The excellent efficacy, safety and tolerability already demonstrated by AL tablets were confirmed with dispersible AL in a large trial comparing the crushed tablets with dispersible tablets in 899 African children with falciparum malaria. In the evaluable population, 28-day PCR-corrected cure rates of >96% were achieved. Further, its sweet taste means that it is palatable for children, and the dispersible formulation makes it easier for caregivers to administer than bitter crushed tablets. Easing administration may foster compliance, hence improving therapeutic outcomes in infants and young children and helping to preserve the efficacy of ACT.

Figure 1

Similar efficacy across body weight groups with crushed AL tablet and dispersible AL tablet (PCR-corrected cure rate in the modified intent-to-treat population). Adapted from Abdulla et al [12].

Figure 2

Similar median time to parasite clearance with crushed AL tablets and dispersible AL tablets (among patients with fever at baseline). Adapted from Abdulla et al [12].

Figure 3

Similar median time to fever clearance is with crushed AL tablets and dispersible AL tablets. Adapted from Abdulla et al [12].

Figure 4

Coartem^® Dispersible packaging.

Figure 5

Step-by-step instructions on how to make up the dispersible AL tablets for easy administration to children. The tablet disperses in a small amount of water to produce a sweet-tasting solution.