What is the recommended dosage and administration of Mefloquine (Lariam) prophylaxis for travelers to areas with chloroquine-resistant malaria?

Mefloquine Prophylaxis for Chloroquine-Resistant Malaria

For travelers to areas with chloroquine-resistant P. falciparum, mefloquine 250 mg weekly is a first-line prophylactic option, started 1-2 weeks before travel, continued weekly during exposure, and for 4 weeks after leaving the endemic area. 1, 2

Dosing Algorithm

Adult Dosing

• Standard dose: 250 mg (one tablet) once weekly 2
• Timing to start: 1 week before arrival in endemic area (or 2-3 weeks before if taking other medications to assess drug interactions) 2
• During travel: Continue weekly on the same day each week, preferably after the main meal 2
• After departure: Continue for 4 additional weeks to ensure suppressive blood levels when merozoites emerge from the liver 2
• Administration: Never on empty stomach; take with at least 8 oz (240 mL) of water 2

Pediatric Dosing

• Weight >45 kg: One 250 mg tablet weekly 2
• Weight 30-45 kg: 3/4 tablet weekly 2
• Weight 20-30 kg: 1/2 tablet weekly 2
• Weight <20 kg: Limited experience; use alternative agents 2
• Tablets may be crushed and suspended in water, milk, or other beverage for children unable to swallow whole 2

When to Choose Mefloquine vs. Alternatives

Use mefloquine as first-line when: 1, 3

• Traveling to high-risk chloroquine-resistant areas (sub-Saharan Africa, Southeast Asia except mefloquine-resistant zones)
• Patient can tolerate weekly dosing schedule
• No contraindications present (see below)

Choose doxycycline 100 mg daily instead when: 1, 3

• Traveling to mefloquine-resistant areas (Thai-Cambodian and Thai-Myanmar borders, parts of East Asia)
• Patient has contraindications to mefloquine
• Short-term travel where daily dosing is acceptable

Choose atovaquone-proguanil when: 1

• Shorter post-travel prophylaxis preferred (7 days vs. 4 weeks)
• Patient intolerant to both mefloquine and doxycycline

Critical Contraindications

Absolute contraindications to mefloquine: 4, 1, 3, 2

• History of seizures or epilepsy
• Active or history of serious psychiatric disorders (depression, anxiety disorder, psychosis, schizophrenia)
• Severe liver impairment
• Hypersensitivity to mefloquine or related compounds

Relative contraindications: 4, 2

• Occupations requiring precision movements (pilots, machine operators)
• Cardiac conduction abnormalities
• First trimester of pregnancy (second and third trimesters acceptable per WHO/CDC) 5

Neuropsychiatric Side Effects: The Major Pitfall

70% of neuropsychiatric adverse events occur within the first three doses. 1 This is the most critical monitoring period.

Frequency and Manifestations

• Severe neuropsychiatric effects: 0.01% to higher rates in British experience 4, 1
• Symptoms include: Anxiety, depression, sleep disturbances, nightmares, hallucinations, dizziness, frank psychotic attacks, or convulsions 4, 1, 6
• Troublesome effects requiring discontinuation: 8.8% of females, 2.6% of males in one study 7

Management Strategy

• Start 2-3 weeks before departure (rather than 1 week) if possible to identify intolerance before travel 2
• Discontinue immediately if severe mood changes, hallucinations, or seizures develop 1
• Never use mefloquine for self-treatment due to high frequency of side effects at therapeutic doses 4

Efficacy Data

Mefloquine demonstrates 99-100% protective efficacy against chloroquine-resistant P. falciparum in high-quality trials. 8 In a randomized controlled trial of Indonesian soldiers, 0 of 68 soldiers on mefloquine developed malaria versus 53 of 69 on placebo (protective efficacy 100%, CI 96-100%) 8. A comprehensive review found protective efficacy >91% in nonimmune travelers except in clearly defined multi-drug resistant regions 5.

Special Population Considerations

Pregnancy

• Second and third trimesters: Acceptable per WHO and CDC recommendations 5
• First trimester: Avoid if possible; use chloroquine with standby Fansidar treatment instead 4
• Early animal studies showed teratogenic effects at high doses, but cumulative human evidence is reassuring 5

Children

• Safe in children >20 kg with weight-based dosing 2
• Children <15 kg should use chloroquine instead 1

Pregnant Women and Young Children Alternative

• Use chloroquine 300 mg base weekly with standby Fansidar for presumptive self-treatment if fever develops and medical care unavailable 4, 1

Compliance: The Leading Cause of Prophylaxis Failure

Most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens. 4, 1, 3 The 4-week post-exposure continuation is critical—this is when liver-stage parasites emerge into the bloodstream 2.

Compliance Rates

• Complete compliance with mefloquine: 78.2% in one study 7
• Discontinuation due to adverse effects: 6.3% overall (8.8% females, 2.6% males) 7

Additional Considerations

Relapsing Malaria (P. vivax and P. ovale)

• Mefloquine does not eliminate liver-stage parasites 2
• Add primaquine 30 mg base daily during the last 2 weeks of the 4-week post-exposure period for travelers with prolonged exposure (missionaries, Peace Corps volunteers) 4, 1
• Mandatory G6PD testing required before primaquine use 1

Treatment Failure

• If prophylaxis with mefloquine fails, do not use mefloquine for treatment 2
• Carefully evaluate alternative antimalarials for therapy 2

Geographic Resistance Patterns

• Sub-Saharan Africa: Low but increasing resistance 5
• Thai-Cambodian and Thai-Myanmar borders: Multi-drug resistance including mefloquine; use doxycycline instead 4, 3

Loading Dose Strategy

• 250 mg daily for 3 days followed by weekly dosing achieves steady-state in 4 days versus 7-9 weeks 5
• However, this is associated with higher incidence of adverse events 5
• Not routinely recommended in standard guidelines 2