Antimalarial drug toxicity: a review

Antimalarial drug toxicity is viewed differently depending upon whether the clinical indication is for malaria treatment or prophylaxis. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is inevitable. As chloroquine resistance has become widespread, alternative agents may be used in treatment regimens, however, the toxicity of these antimalarial agents should be considered. Quinine is the mainstay for treating severe malaria due to its rare cardiovascular or CNS toxicity, but its hypoglycemic effect may be problematic. Mefloquine can cause dose-related serious neuropsychiatric toxicity and pyrimethamine-dapsone is associated with agranulocytosis, especially if the recommended dose is exceeded. Pyrimethamine-sulfadoxine and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Atovaquone/proguanil is an antimalarial combination with good efficacy and tolerability as prophylaxis and for treatment. The artemisinin derivatives have remarkable efficacy and an excellent safety record. Prescribing in pregnancy is a particular problem for clinicians because the risk-benefit ratio is often very unclear.