Mefloquine

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Chapter: Essential pharmacology : Antimalarial Drugs

It is a drug developed to deal with the problem of chloroquine resistant P. falciparum, and has emerged from reinvestigation of quinoline methanols that were originally tested during World War II.


MEFLOQUINE

 

It is a drug developed to deal with the problem of chloroquine resistant P. falciparum, and has emerged from reinvestigation of quinoline methanols that were originally tested during World War II. Mefloquine is a relatively fastacting erythrocytic schizontocide, slower than chloroquine or quinine; effective against chloroquine-sensitive as well as resistant plasmodia. In field trials, single dose (15 mg/kg, max 1 g) has rapidly controlled fever and eliminated circulating parasites in infections caused by P. falciparum or P. vivax in partially immune as well as nonimmune individuals. However, like chloroquine, relapses occur subsequently in vivax malaria. It is also an efficacious suppressive prophylactic for multiresistant P. falciparum and other types of malaria. Mefloquine-resistance among P. falciparum has become common in Thailand, Cambodia and Myanmar, but is sporadic in Africa, South America and Middle east. Since it has not been extensively used in India, mefloquine-resistance is not a problem yet, but due to its long t½ chances of selection of resistant strains are high; mefloquine-resistant P. falciparum isolates have been reported from Gujarat and Andhra Pradesh. Resistance to mefloquine confers cross resistance to quinine and halofantrine.

 

The mechanism of action of mefloquine is not known, but the morphological changes produced in the intraerythrocytic parasite resemble quinine. It is actively taken up even by chloroquine-resistant P. falciparum and, like chloroquine raises intravesicular pH. It appears to bind to haeme and the complex damages membranes of the parasite. Resistant organisms accumulate less mefloquine.

 

Pharmacokinetics

 

Oral absorption of mefloquine is good but quite slow. It is highly plasma protein bound and concentrated in many organs including liver, lung and intestines. Extensive metabolism occurs in liver and it is primarily secreted in bile. Considerable enterohepatic circulation of mefloquine and its tissue binding accounts for the long t½ which is 2–3 weeks.

 

Adverse Effects

 

Mefloquine is bitter in taste; common reaction is dizziness, nausea, vomiting, diarrhoea, abdominal pain and sinus bradycardia. These are usually mild and largely dose related, but may be severe in some. Major concern has been a variety of neuropsychiatric reactions (disturbed sense of balance, ataxia, errors in operating machinery, strange dreams, anxiety, hallucinations, rarely convulsions) occurring in some recipients. These are dose related and subside in 1–3 weeks. Rare events are haematological, hepatic and cutaneous toxicity. Mefloquine appears to be safe during pregnancy, but should be avoided in 1st trimester unless absolutely essential.

 

Interactions

 

Halofantrine or quinidine/quinine given to patients who have received mefloquine cause QTc lengthening—cardiac arrests are reported. Exaggerated bradycardia or arrhythmias were apprehended when mefloquine is given to patients on β blockers, Ca2+ channel blockers, digitalis and antidepressants, but no such reactions have occurred and comedication with these drugs is no longer contraindicated (WHO 1996).

 

Use

 

Mefloquine is an effective drug for multiresistant P. falciparum. Because of its potential toxicity, cost and long t½, its use is being restricted to areas where such strains are prevalent. To check the spread of mefloquine-resistance, current recommendation is to use it only along with the rapidly acting drug artesunate, as ACT for uncomplicated chloroquine as well as S/P resistant falciparum malaria. For vivax malaria, it should be used only in the rare case of the parasite being both chloroquine and quinine + doxycycline resistant. Mefloquine cannot be given parenterally and is not used in complicated/ cerebral malaria.

 

For prophylaxis of malaria among travellers to areas with multidrug resistance; 5 mg/kg (adults 250 mg) per week is started preferably 2–3 weeks before travel to assess side effects in the individual. Not recommended for prophylaxis in residents of the endemic area.

 

MEFLOTAS, MEFLIAM, CONFAL, FACITAL 250 mg tab; to be taken with plenty of water after meals.

 

Mepacrine (Quinacrine, Atabrine)

 

It is an acridine derivative erythrocytic schizontocide, more toxic and less effective than chloroquine. It is obsolete as an antimalarial, but is also active against giardia and tapeworms.

 

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