CNS ADVERSE EVENTS ASSOCIATED WITH ANTIMALARIAL AGENTS - FACT OR FICTION

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are as sociated with the quinoline and artemisinin derivatives. Chloroquine, once considered too toxic for humans, has been the antimalarial of cho ice for 40 years. While a range of serious CNS effects have been docum ented during chloroquine therapy, the incidence is unclear (extrapyram idal symptoms occur with an incidence of 1 in 5000). Amodiaquine has a higher incidence of mild CNS effects than chloroquine. Mefloquine the rapy causes dose-related transient dizziness. Serious CNS events durin g mefloquine therapy occur in 1 : 1200 Asians and 1 : 200 Caucasians/A fricans. Risk factors include dosage, concomitant drug use/interaction s, previous history of a CNS event and disease severity. Retreatment ( within a month) increases the risk in Asians 7-fold. Studies indicate that the frequency of serious CNS events with mefloquine prophylaxis ( 1 : 10 000) is similar to that with chloroquine (1 : 13 600). Quinine causes cinchonism at standard therapeutic doses. High-tone hearing los s occurs, but irreversible auditory or ocular effects are very rare. T he artemisinin derivatives are associated with dose-dependent brain le sions in rodent, canine and nonhuman primates. At low doses, histologi cal injury has been demonstrated, without clinical neurological signs. No significant toxicity has been reported in humans. Other antimalari al drugs are seldom associated with CNS adverse events. Data do not su ggest a need to diminish the correct use of the quinoline derivatives. Irreversible effects are extremely rare and usually associated with o verdosing or prior history of a serious CNS event. Concomitant therape utic use of 2 drugs from the same family, or retreatment with the same drug, should be avoided. Onset of drug-associated serious CNS events requires drug discontinuation and future avoidance of the drug.