Mefloquine
Antimalarials
Antimalarials
Long-acting quinoline for malaria prevention in travellers and as a last-choice treatment; its boxed warning is lasting neuropsychiatric effects.
Quick facts
- Group
- Antimalarials
- Target
- Not fully defined: binds hemozoin like chloroquine; one study showed it binding the P. falciparum 80S ribosome
- Key effects
- Vivid dreams · Nausea · Anxiety and mood changes
- Monitor
- Psychiatric history before prescribing · New anxiety
- ATC
- P01BC02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows mefloquine bound to the Plasmodium falciparum 80S ribosome (cryo-EM), one proposed target; its action may also involve heme, like other quinolines.
A quinoline methanol and a potent blood schizonticide. It associates with hemozoin, suggesting a chloroquine-like action on heme, but resistance linked to the parasite's PfMDR1 transporter suggests its target lies outside the food vacuole; it has also been shown to bind the parasite ribosome and block protein synthesis. It does not act on liver hypnozoites. Its very slow elimination makes it useful for weekly prophylaxis but favours resistance when used alone.
- Reaches blood-stage parasites in red cells
- Interferes with heme handling and protein synthesis
- Blood stages die; liver hypnozoites survive
- Lingers for weeks: weekly prophylaxis possible
Indications
- Prophylaxis in travellers to areas where it is still effective Malaria →
- Treatment of uncomplicated malaria only when no other option is available (CDC); with artesunate it forms an ACT Malaria →
Adverse effects
Common
- Vivid dreams, insomnia, dizziness and headache
- Nausea, vomiting, diarrhoea and abdominal pain
- Anxiety and mood changes
- Muscle pain and sweating
Contraindications
- History of seizures, depression, anxiety disorder, psychosis or other major psychiatric disorder
- Hypersensitivity to mefloquine, quinine or quinidine
- Halofantrine during or after mefloquine
- Caution: heart conduction disorders, liver disease; infections from parts of Southeast Asia (resistance)
Key interactions
- Quinine, quinidine and chloroquine
- Additive cardiac toxicity and convulsions; quinine soon after mefloquine is hazardous
- Halofantrine and ketoconazole
- Dangerous QT prolongation (risk persists for weeks after mefloquine)
- Anticonvulsants (carbamazepine, phenytoin, valproate, phenobarbital)
- Mefloquine lowers seizure control
- Rifampicin
- Induces CYP3A4 and lowers mefloquine levels
What is monitored
- Psychiatric history before prescribing
- New anxiety, depression, restlessness, confusion or vertigo: the drug is stopped
- ECG in patients with heart disease or other QT drugs
- Liver function and vision with long use
Administration and safety
- Oral, with food and a full glass of water; tablets may be crushed into a liquid.
- Prophylaxis is weekly, starting before travel and continuing after return.
- If vomiting occurs within the first hour, the prescriber decides on repeating the dose.
- Not used as single therapy for infections acquired in parts of Southeast Asia (resistance).
Pregnancy and breastfeeding
Animal data at high doses show harm and an increase in stillbirths has been suggested; pregnancy is avoided for about 3 months after use because of its long half-life.
Nursing care
- Before: screen for seizures, depression, anxiety and psychosis; record other heart drugs.
- Give the patient the medication guide and warn about dizziness and balance problems (driving, operating machinery).
- Teaching: stop and seek care for sudden anxiety, depression, confusion, hallucinations or vertigo.
- Prophylaxis lowers but does not remove the risk: insect repellent and bed nets are still needed; contraception during use and for some months after.
Pharmacokinetics
- Absorption
- Oral only (injections cause severe local reactions); absorbed with marked variability
- Distribution
- Very lipophilic, extensive tissue uptake, about 98 % bound to plasma proteins
- Metabolism
- Liver CYP3A4 (inhibited by ketoconazole, induced by rifampicin)
- Elimination
- Mostly in faeces; a small fraction unchanged in urine
- Half-life
- Long and variable: 13 to 24 days
Test yourself
Think of the answer, then tap the question to see it.
What does mefloquine's boxed warning describe?
Neuropsychiatric effects (anxiety, depression, psychosis, seizures) and vestibular effects (vertigo, tinnitus, loss of balance) that can persist or be permanent.
Why can mefloquine be taken only once a week for prophylaxis?
It has a very long half-life (weeks), so blood levels stay effective between weekly doses.
In whom is mefloquine contraindicated?
People with a history of seizures or major psychiatric disorders (depression, anxiety, psychosis), and those allergic to mefloquine, quinine or quinidine.
Connections
← Back to the class: Antimalarials
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Mefloquine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Malaria in the United States: Treatment Tables (Centers for Disease Control and Prevention (CDC), 2026); Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. (RCSB Protein Data Bank (entry 5UMD), 2017).
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Representative model, for educational purposes only.