Mefloquine

This is a long-acting product (after 2 to 3 weeks half of the dose is still present). There is also a combination of mefloquine + pyrimethamine + sulphadoxine (Fansimef®). Mefloquine has a rather slow onset of action.

Mefloquine, curative use

The curative dose of mefloquine for an adult is 500 mg orally, to be repeated after 12 hours and after 24 hours (sometimes 750-500-250 mg is also given). In Europe the dose is expressed as the base (250 mg base = 274 mg mefloquine hydrochloride) while in the USA it is expressed as the salt (250 mg salt = 228 mg base). Therefore, a 500 mg dose in the USA gives approximately 10% less active drug than in Europe. There is no injectable form. The action of mefloquine upon the myocardium is the same as that of quinine. There must be an interval of 12 hours between the last dose of quinine and taking mefloquine (quinine is removed rapidly from the body). During treatment of an attack mefloquine may be given if there is renal insufficiency (a common problem in severe malaria). At curative doses there are quite often unpleasant side effects, such as nausea, insomnia, tremor, anxiety and more rarely convulsions or psychotic episodes.

Mefloquine, preventive use

Mefloquine plays an important role in prophylaxis. The product is 98% bound to plasma proteins. Breakdown to an inactive metabolite occurs in the liver. Excretion is mainly via the liver and biliary route, and to a very limited extent via the kidneys. The plasma half-life is 2 to 3 weeks. Ingestion of 1 tablet per week produces stable blood levels after 7 weeks. This may be drastically shortened by taking a loading dose over 3 days (1 tablet per day x 3 consecutive days). Traditionally it is said that mefloquine prophylaxis should be started before departure. This guideline is based on the consideration that intolerance to the drug can be monitored in this way. It is safe to begin the medication 15 days before departure so that 3 tablets are taken before leaving. In this way 75% of the side effects can be detected. At the prophylactic dosage (adults one 250 mg tablet per week) side effects occur in 2 to 3% of people, which require that the prophylaxis be discontinued. Rarely (1 in 12,000 to 15,000) preventive dosages may trigger epilepsy or psychosis may occur. Epilepsy and arrhythmias (including the use of beta-blockers, calcium antagonists and digitalis) are contra-indications for the use of this product. The product was initially not recommended in pregnant women, but in practice has proved to be safe in the second and third trimesters. The prophylactic use of mefloquine used to be limited to 3 months, but new data indicate that the product is safe if taken for longer. It is best if people who carry out critical motor operations (e.g. aeroplane pilots) do not take mefloquine. In 1994 an anecdotal case was described, of a central anticholinergic syndrome (delirium and stupor, mydriasis, hyperpyrexia) after taking mefloquine. This was very swiftly reversible after injecting 2 mg physostigmine (a cholinesterase inhibitor similar to prostigmine).

Mefloquine, resistance

The first case of mefloquine resistance was described in Thailand in 1982. There is already mefloquine resistance on a small scale in many countries, but this can be significant locally: e.g. the cure rate in East Thailand was only 41% in 1993. P. falciparum malaria can thus sometimes occur in spite of correct prophylactic use of mefloquine. Mefloquine does not kill sporozoites (therefore P. vivax and P. ovale malaria are still possible after leaving an endemic zone and after discontinuing mefloquine).

Category: Medicine Notes