Practical info Artesunate is dispensed as a powder of artesunic acid, which is dissolved in sodium bicarbonate (5%) to form sodium artesunate. The solution is then diluted in approximately 5 mL of 5% dextrose and given by intravenous injection or by intramuscular injection into the anterior thigh. The solution should be prepared freshly for each administration and should not be stored. Artesunate is rapidly hydrolysed in-vivo to dihydroartemisinin, which provides the main antimalarial effect. Studies of the pharmacokinetics of parenteral artesunate in children with severe malaria suggest that they have less exposure than older children and adults to both artesunate and the biologically active metabolite dihydroartemisinin. Body weight has been identified as a significant covariate in studies of the pharmacokinetics of orally and rectally administered artesunate, which suggests that young children have a larger apparent volume of distribution for both compounds and should therefore receive a slightly higher dose of parenteral artesunate to achieve exposure comparable to that of older children and adults. Artesunate and post-treatment haemolysis Delayed haemolysis starting >1 week after artesunate treatment of severe malaria has been reported in hyperparasitaemic non-immune travellers. Between 2010 and 2012, there were six reports involving a total of 19 European travellers with severe malaria who were treated with artesunate injection and developed delayed haemolysis. All except one were adults (median age, 50 years; range, 5–71 years). In a prospective study involving African children, the same phenomenon was reported in 5 (7%) of the 72 hyperparasitaemic children studied. Artesunate rapidly kills ring-stage parasites, which are then taken out of the red cells by the spleen; these infected erythrocytes are then returned to the circulation but with a shortened life span, resulting in the observed haemolysis. Thus, post-treatment haemolysis is a predictable event related to the life-saving effect of artesunate. Hyperparasitaemic patients must be followed up carefully to identify late-onset anaemia.

Other considerations Individual parenteral artesunate doses between 1.75 and 4 mg/kg have been studied and no toxicity has been observed. The GRC concluded that the predicted benefits of improved antimalarial exposure in children are not at the expense of increased risk.