Mefloquine malaria

Mefloquine (t) 21 d) is similar in several respects to quinine although it does not intercalate with plasmodial DNA. It is used for malaria chemoprophylaxis, to treat uncomplicated Plasmodium falciparum (both chloroquine-sensitive and chloroquine resistant) and chloroquine-resistant Plasmodium vivax malaria. Mefloquine is rapidly absorbed from the gastrointestinal tract and its action is terminated by metabolism. When used for prophylaxis, 250 mg (base)/week should be taken, commencing 1-3 weeks before entering and continued for 4 weeks after leaving a malarious area. It should not be given to patients with hepatic or renal impairment. 

The recently introduced antimalanal halofantrine (6) is an orally active blood schizonucide reported to be more than 95% effective in the treatment of malaria [S] Mefloquine hydrochloride (7) contmues to be useful m the prophylaxis and treatment of malaria [9]... 

Malaria, a tropical disease caused by protozoan parasites of the genus Plasmodium, has been a major concern for centuries and has now extended to a great deal of the world s population, killing every year 1-2 million people. Different medicines are in use to cure or to prevent malaria. The classical natural medicine quinine was soon replenished with synthetic compounds such as primaquine, chloroquine and mefloquine. However, a major problem is still an increasing resistance towards these compounds. 

The Plasmodium falciparum malaria PD model successfully described the antimalarial effect of artemisinin, mefloquine, and a combination of the two drugs... 

Svensson, U.S., Alin, H., Karlsson, M.O., Bergqvist, Y., and Ashton, M., Population pharmacokinetic and pharmacodjmamic modeling of artemisinin and mefloquine enantiomers in patients with falciparum malaria, Eur.. Clin. Pharmacol, 58, 339-351, 2002. 

Q56 When dispensing mefloquine as a prophylaxis against malaria, the patient should be advised that ... 

Patients taking mefloquine as prophylaxis against malaria should be advised to take the medication regularly and to avoid mosquito bites. Dizziness may be caused by mefloquine and patients should be informed about this side-effect. 

Q38 Chemoprophylaxis of malaria with mefloquine can be undertaken with caution in ... 

Antimalarial drugs are designed to prevent or treat malaria. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. 

Mefloquine is also a 4-aminoquinoline. It is a blood schizonticide active against the asexual stages of all malaria parasites. Mefloquine is currently the prophylactic agent of choice for short-term travellers. Resistance of P. falciparum against mefloquine has occurred in South-East Asia. Only an oral... 

For uncomplicated falciparum malaria there are several options (with the major drawback in brackets) halofantrine (arrhytmia), mefloquine (neurotoxicity), quinine (vomiting, tinnitus), artemether (recrudescence), atovaquone-proguanil (possible fast development of resistance). 

Three currently-used artemisinin based combination therapies (ACT) artesunate-mefloquine, artemether-lumefantrine and dihydroartemisinin-piperaquine, have been proven highly simple, safe and effective in the treatment of multidrug resistant P. falciparum malaria. 

Artesunate x 3 days + mefloquine has been used in several Asian countries for MDR falciparum malaria. Artesunate 4 mg/kg/day x 3 day and mefloquine 25 mg/kg single splitting into 2 dose 6-8 hours apart (15 mg/kg then 10 mg/kg). 

Non-falciparum malaria (like P. vivax) can still be treated with chloroquine although chloroquine resistant P. vivax has been reported from Irian Jaya and Papua New Guinea. In those areas treatment with mefloquine is recommended. To treat the liverstages an additional 2-3 weeks treatment with primaquine is given. It appears that tafenoquine (dosed once a week), a new 8-aminoquinoline, would be a better replacement for primaquine in preventing relapses in P. vivax malaria. 

Mefloquine (Lariam) is a 4-quinohnemethanol derivative used both prophylactically and acutely against resistant P. falciparum malaria. It is ineffective against the hver stage of P vivax malaria. 

While its detailed mechanism of action is unknown, it is an effective blood schizonticide that is, it acts against the form of the parasite responsible for chnical symptoms. Orally administered mefloquine is well absorbed and has an absorption half-hfe of about 2 hours the elimination half-hfe is 2 to 3 weeks. Among its side effects are vertigo, visual alterations, vomiting, and such CNS disturbances as psychosis, hallucinations, confusion, anxiety, and depression. It should not be used concurrently with compounds known to alter cardiac conduction or prophylactically in patients operating dangerous machinery. It should not used to treat severe malaria, as there is no intravenous formulation. 

Antimalarials Mefloquine is a major drug for malaria, in particular, for chloroquine-resistant malaria." However, some cases of neuropsychiatric adverse events and the apparition of resistance tend to limit its use. Metabolism into inactive and phototoxic 1 -7/-2-oxoquinoline is blocked by the presence of the CF3 group." Instead of performing the resolution of enantiomers at the end of the synthesis," the asymmetric reduction of the carbonyl group in the presence of ruthenium catalyst and a chiral diphosphine provided mefloquine with an excellent enantiomeric excess (Figure 8.25). °... 

Mefloquine is effective therapy for many chloroquine-resistant strains of P falciparum and against other species. Although toxicity is a concern, mefloquine is one of the recommended chemoprophylactic drugs for use in most malaria-endemic regions with chloroquine-resistant strains. 

Mefloquine is effective in treating most 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 malaria in a number of countries in Asia and South America. 

Primaquine has been studied as a daily chemoprophylactic agent. Daily treatment with 30 mg (0.5 mg/kg) of base provided good levels of protection against falciparum and vivax malaria. However, potential toxicities of long-term use remain a concern, and primaquine is generally recommended for this purpose only when mefloquine, Malarone, and doxycycline cannot be used. 

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