Artesunate combination studies

The artemisinin derivatives are limited by an unacceptable incidence of recrudescence with monotherapy, and they therefore need to be used in combination. A summary of prospective trials that looked specifically for adverse effects showed that artemisinins alone are very well tolerated (10). The same study showed no evidence of adverse interactions of artesunate with mefloquine, with an incidence of adverse effects similar to that expected from malaria and mefloquine (25 mg/kg) together. Reducing doses of mefloquine increases recrudescence rates to unacceptable levels (11). Combinations of artemisinins with quinine, co-trimoxazole, and doxycycUne are well tolerated. 

Co-administration of artemisinin derivatives, such as artesunate, with deferoxamine may be useful in patients with cerebral malaria, because of the combination of rapid parasite clearance by the former and central nervous system protection by the latter. Artesunate has been studied alone and in combination with deferoxamine in a singleblind comparison (40). Adverse effects were generally mild and there were no differences between the two regimens. 

Nervous system Artesunate and mefloquine are the recommended first-line drugs for uncomplicated malaria in much of South East Asia. However, there are no detailed studies of the potential central nervous system effects of this combination in very young children. In 91 children with uncomplicated malaria, who were randomized to artesunate monotherapy (n = 45) for 7 days or artesunate for 7 days plus mefloquine on days 7 and 8 (n = 46), coordination and behavior were assessed on days 0,7,9,10,14, and 28 [25 ]. As controls, 36 non-febrile children from the same population were tested on days 0,7,14, and 28. The presence of malaria and fever had significant negative effects, but antimalarial treatment did not. 

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