Tests in rodents have shown a brain stem toxicity, which is now being debated. Risks of convulsion in children after treatment from cerebral malaria has been observed too. This may be due to the dosing procedure, or other complication involved in cerebral malaria which Artemisinin formulation has not taken into consideration. Also the derivatives are semi-synthetics, and these need further investigation as to their total safety. Resistance began in the early 1960s.
Resistance is either from a recrudescence or recurrences.
Recrudescence is a short-term relapse due to surviving erythrocytic parasites. Recurrence is a long-term relapse, due to hypnozoites of P. vivax . Bearing in mind that sometimes, it is difficult to determined relapses from re-infections. Increase metabolism of the drug, decrease uptake, efflux of the drug from parasitic vesicles. Increased in metabolism is due to increased parasite s metabolising enzymes, an isoenzyme of the cytochrome P-450 that includes aryl hydrocarbon hydroxylases.