Chemical Make-up of Mefloquine (Larium®)

Drug Category: Antimalarials

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.

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

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

Protein Binding: 98%

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.

Half Life: 2-4 weeks

Contraindication: Use of Lariam is contraindicated in patients with a known hypersensitivity to Mefloquineuine or related compounds (eg, quinine and quinidine) or to any of the excipients contained in the formulation. Lariam should not be prescribed for prophylaxis in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders, or with a history of convulsions.

Interaction: Drug-drug interactions with Mefloquine have not been explored in detail. There is one report of cardiopulmonary arrest, with full recovery, in a patient who was taking a beta blocker (propranolol). The effects of Mefloquineuine on the compromised cardiovascular system have not been evaluated. The benefits of Mefloquine therapy should be weighed against the possibility of adverse effects in patients with cardiac disease.

Because of the danger of a potentially fatal prolongation of the QTc interval, halofantrine must not be given simultaneously with or subsequent to Mefloquine.Concomitant administration of Mefloquine and other related compounds (eg, quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions. If these drugs are to be used in the initial treatment of severe malaria, Mefloquine administration should be delayed at least 12 hours after the last dose. There is evidence that the use of halofantrine after Mefloquineuine causes a significant lengthening of the QTc interval. Clinically significant QTc prolongation has not been found with Mefloquineuine alone.

This appears to be the only clinically relevant interaction of this kind with Mefloquine, although theoretically, coadministration of other drugs known to alter cardiac conduction (eg, anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H1-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. There are no data that conclusively establish whether the concomitant administration of Mefloquineuine and the above listed agents has an effect on cardiac function.

In patients taking an anticonvulsant (eg, valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of Mefloquine may reduce seizure control by lowering the plasma levels of the anticonvulsant. Therefore, patients concurrently taking antiseizure medication and Mefloquine should have the blood level of their antiseizure medication monitored and the dosage adjusted appropriately.When Mefloquine is taken concurrently with oral live typhoid vaccines, attenuation of immunization cannot be excluded. Vaccinations with attenuated live bacteria should therefore be completed at least 3 days before the first dose of Mefloquine.

No other drug interactions are known. Nevertheless, the effects of Mefloquine on travelers receiving comedication, particularly diabetics or patients using anticoagulants, should be checked before departure.In clinical trials, the concomitant administration of sulfadoxine and pyrimethamine did not alter the adverse reaction profile.

Drug Interaction
Acenocoumarol--Mefloquine can increase the anticoagulant effect
Anisindione--Mefloquine can increase the anticoagulant effect
Dicumarol--Mefloquine can increase the anticoagulant effect
Halofantrine--Increased risk of cardiac toxicity
Rifampin--Rifampin lowers mefloquine levels
Ritonavir--Mefloquine decreases the effect of ritonavir
Warfarin--Mefloquine can increase the anticoagulant effect
Ziprasidone--Increased risk of cardiotoxicity and arrhythmias

Food Interaction:
1. Avoid alcohol.
2. Take with a full glass of water.
3. Take with food.

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DrugBank Version: 2.5 —
Contact: Craig Knox or Genome Canada Help Desk