What is mefloquine?

What is Mefloquine?

Mefloquine is an orally administered antimalarial medication used for both prevention (chemoprophylaxis) and treatment of malaria, particularly effective against chloroquine-resistant Plasmodium falciparum. 1, 2

Drug Classification and Mechanism

• Mefloquine is a quinoline-methanol antimalarial that functions as a blood schizontocide, meaning it kills the blood-stage parasites of malaria 2, 3
• It is effective against all four species of human malaria parasites: P. falciparum, P. vivax, P. ovale, and P. malariae, as well as the fifth species P. knowlesi 2, 4
• The drug is marketed under the brand name Lariam and is available as mefloquine hydrochloride tablets 1

Clinical Indications

Malaria Prophylaxis

• Mefloquine is the recommended first-line agent for travelers to areas with chloroquine-resistant P. falciparum malaria 5
• The standard prophylactic dose is 250 mg weekly for adults, taken after the largest meal of the day with at least 8 ounces of water 5, 1
• Prophylaxis should begin 1-3 weeks before travel, continue during travel, and for 4 weeks after leaving the malarious area 5, 1
• Protective efficacy exceeds 91% in nonimmune travelers, with one study demonstrating 100% efficacy against P. falciparum 6, 7

Malaria Treatment

• Mefloquine is effective as single-dose therapy for all malaria species, including multi-drug-resistant P. falciparum 2, 3
• However, mefloquine should not be used for self-treatment due to the frequency of side effects, especially dizziness, associated with therapeutic doses 5

Pharmacokinetics

• Mefloquine is absorbed with a half-life of 1-4 hours, reaching peak blood concentrations at 7-24 hours (median 16.7 hours) after administration 3
• The terminal elimination half-life is extremely long, ranging from 13.8 to 40.9 days (median 20 days) 3
• Food significantly increases bioavailability, which is why it must be taken with meals 1, 7
• The drug has high plasma protein binding exceeding 98% and a large volume of distribution (median 19.2 L/kg) 3

Serious Safety Concerns and Contraindications

Neuropsychiatric Effects

• The most notable adverse effects are neuropsychiatric disturbances, including severe anxiety, paranoia, hallucinations, depression, and suicidal ideation 1, 5
• Serious neuropsychiatric effects occur in approximately 0.01% of users, though some data suggest higher frequencies 5
• These effects typically occur early, with 70% arising from the first three doses 5
• Mefloquine is absolutely contraindicated in patients with depression, recent mental problems (including anxiety disorder, schizophrenia, or psychosis), or history of seizures 1

Cardiac Effects

• Do not combine mefloquine with halofantrine or ketoconazole, or within 15 weeks of the last mefloquine dose, due to risk of fatal QT prolongation 1
• Avoid concurrent use with quinine or quinidine due to serious cardiac arrhythmia risk 1
• Erythromycin should not be used with mefloquine due to additive cardiac conduction effects 8

Neurological Effects

• Dizziness, vertigo, tinnitus, and loss of balance can persist for months to years after stopping mefloquine or may become permanent 1
• Convulsions may occur in patients with epilepsy or when combined with quinine or chloroquine 1

Special Populations

Pregnancy and Lactation

• The WHO and CDC sanction mefloquine use during the second and third trimesters of pregnancy 7, 4
• Some authorities (CDC) allow use even in the first trimester 4
• Inadvertent pregnancy while using mefloquine is not grounds for pregnancy termination 4
• Women should use birth control while taking mefloquine and for 3 months after stopping 1
• Mefloquine chemoprophylaxis is allowed during breastfeeding, though the drug passes into breast milk 1, 4

Pediatric Use

• Mefloquine is not indicated for children weighing less than 15 kg (30 lbs) 5, 1
• Safety and efficacy in children under 6 months for malaria treatment is not established 1
• Tablets may be crushed and mixed with water, milk, or other beverages for children unable to swallow whole tablets 1

Common Adverse Effects

• The most common side effects include nausea, vomiting, diarrhea, headache, dizziness, rash, pruritus, and abdominal pain 2
• These effects are generally transient and self-limited at prophylactic doses 5
• The incidence of adverse events ranges from 12-90% for any adverse event, with 11-17% of travelers experiencing some degree of incapacitation 7
• Women and individuals with low body weight may have increased propensity for neuropsychiatric adverse events 4

Drug Resistance

• Mefloquine resistance is established in certain areas of Thailand and parts of Southeast Asia (Burma, Cambodia) and the Amazon basin 5, 2
• Resistance may be increasing in sub-Saharan Africa, though levels remain low 7
• Mefloquine resistance is associated with halofantrine and quinine resistance but not with chloroquine resistance 7

Important Clinical Considerations

• Avoid activities requiring alertness and fine motor coordination (driving, operating heavy machinery) until you know how mefloquine affects you 1
• Patients using mefloquine for a year or longer require monitoring of eye function and liver function 1
• If fever develops after leaving a malarious area, contact a doctor immediately even while taking prophylaxis 1
• Medicine alone does not prevent malaria; use protective clothing, insect repellents, and bednets to avoid mosquito bites 1

Alternatives to Mefloquine

• Doxycycline (100 mg daily) is an alternative for short-term travelers intolerant of mefloquine or for whom it is contraindicated 5
• Chloroquine remains appropriate for areas without chloroquine resistance 5
• For pregnant women and children under 15 kg who cannot use mefloquine, chloroquine with standby Fansidar treatment may be considered 5