Chemoprophylaxis—Mefloquine is effective in prophylaxis against most strains of P falciparum and probably all other human malarial species. Mefloquine is therefore among the drugs recommended by the CDC for chemoprophylaxis in all malarious areas except those with no chloroquine resistance (where chloroquine is preferred) and some rural areas of Southeast Asia with a high prevalence of mefloquine resistance. As with chloroquine, eradication of P vivax and P ovale requires a course of primaquine.
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Treatment—Mefloquine is effective in treating uncomplicated falciparum malaria. The drug is not appropriate for treating individuals with severe or complicated malaria, since quinine, quinidine, and artemisinins are more rapidly active, and since drug resistance is less likely with those agents. The combination of artesunate plus mefloquine showed excellent antimalarial efficacy in regions of Southeast Asia with some resistance to mefloquine, and this regimen is now one of the combination therapies recommended by the WHO for the treatment of uncomplicated falciparum malaria (Table 52–4). Artesunate-mefloquine is the first-line therapy for uncomplicated falciparum malaria in a number of countries in Asia and South America.
Weekly dosing with mefloquine for chemoprophylaxis may cause nausea, vomiting, dizziness, sleep and behavioral disturbances, epigastric pain, diarrhea, abdominal pain, headache, rash, and dizziness. Neuropsychiatric toxicities have received a good deal of publicity, but despite frequent anecdotal reports of seizures and psychosis, a number of controlled studies have found the frequency of serious adverse effects from mefloquine to be similar to that with other common antimalarial chemoprophylactic regimens. However, concern about reported long-term effects of short-term use of mefloquine led in 2013 to the FDA adding a black box warning regarding potential neurologic and psychiatric toxicities. Leukocytosis, thrombocytopenia, and aminotransferase elevations have also been reported.
Adverse effects are more common with the higher dosages of mefloquine required for treatment. These effects may be lessened by administering the drug in two doses separated by 6–8 hours. The incidence of neuropsychiatric symptoms appears to be about ten times greater than with chemoprophylactic dosing, with widely varying frequencies of up to about 50% reported. Serious neuropsychiatric toxicities (depression, confusion, acute psychosis, or seizures) have been reported in less than 1 in 1000 treatments, but some authorities believe that these toxicities are actually more common. Mefloquine can also alter cardiac conduction, and arrhythmias and bradycardia have been reported.
Mefloquine is contraindicated in a patient with a history of epilepsy, psychiatric disorders, arrhythmia, cardiac conduction defects, or sensitivity to related drugs. It should not be co-administered with quinine, quinidine, or halofantrine, and caution is required if quinine or quinidine is used to treat malaria after mefloquine chemoprophylaxis. The CDC no longer advises against mefloquine use in patients receiving β-adrenoceptor antagonists. Mefloquine is also now considered safe in young children, and it is the only chemoprophylactic other than chloroquine approved for children weighing less than 5 kg and for pregnant women. Available data suggest that mefloquine is safe throughout pregnancy, although experience in the first trimester is limited. An older recommendation to avoid mefloquine use in those requiring fine motor skills (eg, airline pilots) is controversial. Mefloquine chemoprophylaxis should be discontinued if significant neuropsychiatric symptoms develop.