indication

For the treatment of mild to moderate acute malaria caused by Mefloquineuine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. Also for the prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of Plasmodium falciparum.

pharmacology

Mefloquine is an antimalarial agent which acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.

mechanism of action

Mefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.

toxicity

Oral, rat: LD₅₀ = 880 mg/kg. Symptoms of overdose include nausea, vomiting, and weight loss.

biotransformation

Hepatic. Two metabolites have been identified in humans. The main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, is inactive against Plasmodium falciparum. The second metabolite, an alcohol, is present in minute quantities.

absorption

Well absorbed from the gastrointestinal tract. The presence of food significantly enhances the rate and extent of absorption.

half life

2 to 4 weeks

route of elimination

There is evidence that mefloquine is excreted mainly in the bile and feces. Urinary excretion of unchanged mefloquine and its main metabolite under steady-state condition accounted for about 9% and 4% of the dose, respectively.

drug interactions

Acenocoumarol: Mefloquine may increase the anticoagulant effect of acenocoumarol.

Anisindione: Mefloquine may increase the anticoagulant effect of anisindione.

Artemether: Mefloquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.

Dicumarol: Mefloquine may increase the anticoagulant effect of dicumarol.

Halofantrine: Increased risk of cardiac toxicity

Lumefantrine: Mefloquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Rifampin: Rifampin lowers mefloquine levels

Ritonavir: Mefloquine decreases the effect of ritonavir

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: Telithromycin may reduce clearance of Mefloquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Mefloquine if Telithromycin is initiated, discontinued or dose changed.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Tiagabine: Mefloquine increases the risk of seizure and is contraindicated in persons with a history of convulsions. Possible reduction in the therapeutic effect of Tiagabine when used for other indications may also occur.

Topotecan: The p-glycoprotein inhibitor, Mefloquine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Vigabatrin: Mefloquine may decrease the serum concentration of Vigabatrin. This may increase the risk of seizure in patients receiving Vigabatrin to prevent seizures. Consider alternate therapy or monitor for changes in Vigabatrin serum concentration, therapeutic or adverse effects if Mefloquin is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of mefloquine by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of mefloquine if voriconazole is initiated, discontinued or dose changed.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Warfarin: Mefloquine may increase the anticoagulant effect of warfarin.

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zonisamide: Mefloquine may decrease the serum concentration and therapeutic effect of zonisamide. Concomitant therapy is contraindicated in patients with history of convulsions.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).