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Mefloquine
Mefloquine is a quinoline methanol derivative1 used to prevent and treat malaria,2 including infections resistant to chloroquine.2 It was developed by the United States Army in the 1970s. It can cause serious psychiatric effects, including potentially long-term depression, anxiety, and hallucinations,2 as well as neurological effects such as seizures and impaired balance. It is not recommended for people with a history of mental health problems or epilepsy.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
The upper dosage value listed reflects the highest dose reported in available experience accounts rather than a formally established ceiling.
Subjective Effects
Pharmacology
Pharmacodynamics
Mefloquine acts against blood-stage malaria parasites but does not eliminate liver-stage parasites.2 Its antimalarial mechanism remains incompletely understood;2 studies suggest that inhibition of protein synthesis through the Plasmodium falciparum 80S ribosome contributes to its action. Mefloquine also partially activates 5-HT2A and 5-HT2C receptors, inhibits serotonin reuptake, and antagonizes 5-HT3 and adenosine A2A receptors. Additional actions include acetylcholinesterase inhibition and nonspecific blockade of connexin hemichannels and pannexons, with the latter proposed to contribute to potential antiepileptic activity. Increased Pfmdr1 copy number is associated with parasite resistance to mefloquine,3 and activity against JC virus has also been reported.
Pharmacokinetics
Mefloquine is readily absorbed from the gastrointestinal tract, and food increases its bioavailability by about 40%. Mefloquine reaches its maximum plasma concentration within 6-24 hours after a single oral dose.4 Plasma protein binding exceeds 98%, and extensive tissue distribution produces an apparent volume of distribution of approximately 20 L/kg in healthy adults, with reported estimates of 13.3-40.9 L/kg. It can accumulate in parasite-infected red blood cells2 and appears in breast milk at low concentrations.2 Mefloquine undergoes extensive hepatic metabolism, primarily through CYP3A4, producing a major carboxylic acid metabolite and small amounts of an alcohol metabolite. It is also classified as a CYP3A4 inhibitor and a P-glycoprotein substrate and inhibitor. Elimination occurs primarily through bile and feces, with 4-9% excreted in urine; steady-state recovery measurements include unchanged drug equivalent to 9% of the ingested dose and the carboxylic acid metabolite equivalent to 4%. Reported terminal elimination half-lives range from 0.9-13.8 days in one review, while studies in healthy adults report mean half-lives of 2-4 weeks, averaging approximately 21 days. Systemic clearance estimates range from 0.022-0.073 L/h/kg, with prescribing information reporting 30 mL/min. Clearance increases during pregnancy, whereas impaired liver function can prolong elimination. Plasma half-life remains unchanged during long-term use. The (−)-enantiomer reaches higher plasma concentrations and has a longer half-life than the (+)-enantiomer.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Harm Potential
Toxicity
Reported lowest toxic doses, rather than lethal-dose estimates, are 11 mg/kg over two weeks of intermittent oral administration in humans and 880 mg/kg in rats. Overdose may intensify adverse effects;2 treatment is supportive and symptomatic, and no antidote is known.2
LD50 Data
| Species | Route | Value |
|---|---|---|
| Rat | Intraperitoneal | 130 mg/kg |
Mefloquine can cause serious neurological and psychiatric adverse effects, including balance problems, tinnitus, seizures, depression, anxiety, hallucinations, and unusual behavior.5 Neurological side effects can begin at any time during treatment; vestibular symptoms can persist for months to years after discontinuation or become permanent.5
Mefloquine may cause heart rhythm abnormalities detectable on an electrocardiogram.7
Mefloquine has the potential to cause muscle toxicity.
Psychosis Risk
Mefloquine can cause visual and auditory hallucinations as psychiatric adverse effects,8 and psychosis is a potential adverse effect.2 Psychiatric symptoms may persist after discontinuation;8 use is contraindicated in people with a recent history of psychiatric disorders.
Seizure Risk
Mefloquine can lower the seizure threshold and cause seizures, including severe episodes requiring hospitalization. It is contraindicated in people with a previous history of seizures.
History & Culture
Development and clinical testing
Mefloquine was developed at the Walter Reed Army Institute of Research in the 1970s, shortly after the Vietnam War ended. It was compound number 142,490 among 250,000 antimalarial compounds screened in the research program.…
Legality
By Country
United StatesPrescription only
CanadaPrescription only
SingaporePrescription only
United KingdomPrescription onlyReferences
Source Pages
Citations
Further Reading
Article Status
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