Tailoring formulations to patients in need: Experience with the paediatric formulation of artemether-lumefantrine (Coartem(R) Dispersible) for the treatment of P. falciparum malaria

Abstract

Specially created paediatric formulations have the potential to improve the acceptability, effectiveness and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a paediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated Plasmodium falciparum malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility and stability, and a similar pharmacokinetic profile and bioequivalence to crushed and intact AL tablets. However, despite being the first paediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children >/=5 kg, and its inclusion in WHO Guidelines, there are very few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of clinical experience with AL Dispersible to date. A randomised, phase 3 study that compared the efficacy and safety of AL Dispersible with crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for dispersible and crushed tablets, respectively), and several sub-analyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite dihydroartemisinin. These and other clinical data support the continued use of paediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria, while accompanied by continued monitoring for the emergence of resistance.