Mefloquine (Mefloquine Hydrochloride) - Summary

MEFLOQUINE SUMMARY

Mefloquine hydrochloride is an antimalarial agent available as 250 mg tablets of mefloquine hydrochloride (equivalent to 228 mg of the free base) for oral administration. Mefloquine hydrochloride is a 4-quinolinemethanol derivative with the specific chemical name of (R*,S*)-(±)-α-2- piperidinyI-2,8-bis(trifluoromethyl)-4-quinolinemethanoI hydrochloride. It is a 2-aryl substituted chemical structural analog of quinine. The drug is a white to almost white crystalline compound, slightly soluble in water.

Treatment of Acute Malaria Infections

Mefloquine Hydrochloride Tablets are indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. There are insufficient clinical data to document the effect of mefloquine in malaria caused by P. ovale or P. malariae.

• Note: Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites. To avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (eg, primaquine).

NEWS HIGHLIGHTS

Published Studies Related to Mefloquine

Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine. [2009.09.15]
BACKGROUND: In the context of the increasing resistance to sulfadoxine-pyrimethamine (SP), we evaluated the efficacy of mefloquine (MQ) for intermittent preventive treatment during pregnancy (IPTp)... CONCLUSIONS: MQ proved to be highly efficacious--both clinically and parasitologically--for use as IPTp. However, its low tolerability might impair its effectiveness and requires further investigations.

The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria. [2009.09.02]
BACKGROUND: Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children... CONCLUSION: In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria. [2009.04.09]
BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam, Mephaquin, and Mefloquina-AC Farma) given in combination with artesunate... CONCLUSION: All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.

A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. [2008.11]
The choice of appropriate artemisin-based combination therapy depends on several factors (cost, efficacy, safety, reinfection rate, and simplicity of administration). In this study, we tested the hypothesis that artesunate-mefloquine (Artequin) is as efficacious as artemether-lumefantrine (Coartem) in treatment of uncomplicated Plasmodium falciparum malaria...

An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. [2006.11]
Background Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum...

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Clinical Trials Related to Mefloquine

Mefloquine Bioequivalence Among 3 Commercially Available Tablets. [Completed]
The objective of this study was to determine the bioequivalence among three commercial tablet formulations of MQ, i. e. Lariam, Mephaquin, and Mefloquine-(AC Farma) when given in combination with artesunate.

Azithromycin Plus Chloroquine Versus Mefloquine In the Treatment of Uncomplicated P. Falciparum Malaria. [Completed]

Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine [Recruiting]
Mefloquine is a quinolinemethanol antimalarial that is effective as therapy and prophylaxis for all species of malaria infecting humans, including multi-drug resistant Plasmodium falciparum. The marketed anti-malaria drug consists of two enantiomers of mefloquine.

Mefloquine's clinical utility has been impaired by its association with neuropsychiatric side effects. The pharmacological basis of mefloquine's side effects is not known but two of the most reported hypotheses relate to its action on (i) the adenosine receptor and (ii) its effect on the cholinesterase enzyme. For both of these mechanisms, there is a significant stereoselective activity of the two enantiomers. In vitro studies show that the (-) isomer is 50-100 fold more potent towards adenosine receptors compared with the (+) isomer. In addition, (-)-mefloquine has considerably more anti-cholinesterase activity. It has therefore been hypothesised that (+)-mefloquine may have a better central nervous system (CNS) safety profile compared with either the racemate or (-)-mefloquine.

This study is a randomized, ascending dose, double-blind, active and placebo-controlled, parallel group study in healthy male and female volunteers designed to investigate this hypothesis and to describe the comparative pharmacokinetics of the racemate and the single enantiomer.

Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML) [Recruiting]
The purpose of the study is to explore if mefloquine works to slow or stop the worsening of PML and to better understand PML. We will measure if mefloquine is working by determining if it reduces the level of JC virus in spinal fluid, as well as, clinical and MRI measures.

Azithromycin Plus Chloroquine Versus Mefloquine for the Treatment of Uncomplicated Malaria in Africa [Completed]

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