Adverse Effects of Antimalarials

Abstract

Various drugs are widely used in the prophylaxis and treatment of malaria. In the prevention of malaria in travellers, a careful risk-benefit analysis is required to balance the risk of acquiring potentially serious malaria against the risk of harm from the prophylactic agent. Unfortunately, the information needed to perform accurate analyses of this type is not available for most antimalarials. In the prophylaxis of malaria, chloroquine and proguanil have an excellent safety record, being very rarely associated with severe adverse reactions in the recommended dosages. However, in many parts of the world they are no longer effective prophylactic agents. Pyrimethamine-dapsone (Maloprim) is associated with agranulocytosis, especially if the recommended dose is exceeded, and should be reserved as a second-line agent for travellers to high risk areas. Pyrimethamine-sulfadoxine (Fansidar) and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Mefloquine, a relative newcomer, may provoke severe neuropsychiatric reactions with a frequency of 1 in 15,000 to 20,000 users at the prophylactic dosage. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is acceptable. As chloroquine resistance has become widespread, alternative agents including quinine, mefloquine, pyrimethamine-sulfadoxine, tetracyclines, halofantrine and artemisinin (qinghaosu) and its derivatives may be used in treatment regimens. The therapeutic ratios for chloroquine, quinine and mefloquine are narrow and toxicity is frequent when recommended treatment dosages are exceeded; parenteral administration above the recommended dose range is especially associated with the hazards of cardiac and neurological toxicity.

Xanthones as Antimalarial Agents: Discovery, Mode of Action, and Optimization

“…By the end of 1984, chloroquine-resistant parasites had spread to 40 countries in Asia, Africa, and South America. Multidrugresistant malaria is now commonplace in Southeast Asia, and travelers to this region are advised to take mefloquine or halofantrine -expensive drugs which can cause serious complications including psychiatric or cardiotoxic side effects, respectively [6,7]. Current therapeutic options for treatment of malaria are dwindling and replacement drugs, the endoperoxide artesunate [8] and the naphthoquinoneproguanil combination known as Malarone ® , offer a rather thin wall of opposition to an advancing hyper-mutable parasitic agent [9].…”

Antimalarial Drug Toxicity: A Review

“…In the prevention of malaria in travelers, a careful risk-benefit analysis is required to balance the risk of acquiring potentially serious malaria against the risk of harm from the prophylactic agent. The therapeutic ratios for some antimalarials are narrow, and toxicity is frequent when recommended treatment dosages are exceeded; parenteral administration above the recommended dose range is especially associated with the hazards of cardiac and neurological toxicity [2] . The purpose of this review is to update physicians on the toxicity associated with antimalarial drugs.…”

Toxicity of mefloquine is similar to that of other chemoprophylaxis

“…This view has been challenged by some authorities,2 who argue that the side effects of mefloquine have been greatly underreported. As White recognised in an editorial on mefloquine, this tendency to understate the toxicity of the durg has followed from the poor scientific quality of almost all of the early studies on use of mefloquine 3…”