Meflon

Approved Indications:

A. Malaria (Treatment and Prophylaxis):

• Treatment of mild to moderate uncomplicated Plasmodium falciparum malaria (including chloroquine-resistant strains)
• Treatment of uncomplicated malaria caused by P. vivax, P. ovale, and P. malariae (usually with a partner drug to cover relapse)
• Prophylaxis of malaria in travelers to areas with chloroquine- or multidrug-resistant P. falciparum

Off-label or Clinically Accepted Uses:

• Treatment of P. falciparum malaria in combination with artesunate in artemisinin-based combination therapy (ACT)
• Prophylactic use in long-term travelers or military personnel in endemic regions

Route of Administration: Oral (tablet)

Prophylaxis of Malaria:

• Adults: 250 mg once weekly, starting 1–2 weeks before entering the endemic area, continued weekly during stay, and for 4 weeks after leaving the area
• Children (>5 kg):
  Dosing based on body weight:
• 5–19 kg: 62.5 mg weekly
• 20–30 kg: 125 mg weekly
• 31–45 kg: 187.5 mg weekly
• 45 kg: 250 mg weekly
  (Start and continue same schedule as adults)

Treatment of Acute Uncomplicated Malaria:

• Adults:
  Total dose of 1,250 mg, administered as:
• 750 mg initially, followed by 500 mg after 6–12 hours
• Children (>5 kg):
  Total dose: 20–25 mg/kg, administered in 2 doses:
• 15 mg/kg initially, then 10 mg/kg after 6–12 hours

Special Populations:

• Elderly: Use with caution; increased sensitivity to CNS side effects
• Renal Impairment: No dose adjustment required
• Hepatic Impairment: Use with caution due to hepatic metabolism
• Pregnancy: See section 5

Mefloquine is a blood schizonticide that acts on the erythrocytic stage of the malaria parasite life cycle. Though its precise mechanism is not fully elucidated, it is believed to interfere with parasite heme polymerization, leading to accumulation of toxic heme metabolites. These metabolites damage parasite membranes and lead to cell lysis and death. Mefloquine also disrupts membrane integrity and inhibits parasite growth within infected red blood cells. It is ineffective against liver-stage (exoerythrocytic) parasites.

• Absorption: Well absorbed orally; peak plasma levels in 6–24 hours
• Bioavailability: 85–90%
• Distribution: Extensive tissue distribution; high concentrations in the liver, lungs, and kidneys; crosses the placenta and blood-brain barrier
• Protein Binding: ~98%
• Metabolism: Primarily hepatic via CYP3A4 into inactive metabolites
• Half-life: 2 to 4 weeks (average ~21 days)
• Excretion: Mainly in feces (as metabolites); minor renal elimination

• Pregnancy:
• FDA Category B: No evidence of fetal harm in animal studies; no adequate studies in pregnant women
• Considered safe in the second and third trimesters for both prophylaxis and treatment
• Use in the first trimester only when benefits outweigh risks
• Lactation:
• Excreted in breast milk in small quantities
• Compatible with breastfeeding, especially for prophylactic use

• Primary Class: Antimalarial agent
• Subclass: Quinoline methanol derivative (related structurally to quinine)

• Known hypersensitivity to mefloquine or related compounds (e.g., quinine, quinidine)
• History of:
• Seizure disorders
• Psychiatric conditions (e.g., anxiety, depression, schizophrenia, psychosis)
• Concomitant use with halofantrine or ketoconazole
• Active or recent severe neuropsychiatric illness

• Neuropsychiatric Effects: May cause anxiety, depression, hallucinations, psychosis, or suicidal ideation. May persist after discontinuation
• Seizure Risk: Contraindicated in seizure disorders
• Cardiac Effects: Caution when used with other drugs that prolong QT interval
• CNS Effects: Dizziness, loss of balance, vertigo, or confusion may affect activities like driving
• Hepatic Dysfunction: Use cautiously in hepatic impairment
• Drug Resistance: Avoid using as monotherapy in regions with known mefloquine resistance

Common Side Effects:

• Central Nervous System: Dizziness, insomnia, vivid dreams, headache, anxiety
• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea
• General: Fatigue, malaise, fever

Serious/Rare Side Effects:

• Depression, hallucinations, paranoia, suicidal ideation
• Seizures
• Cardiac arrhythmia or QT prolongation
• Hypersensitivity reactions, including rash and pruritus
• Vestibular disorders (e.g., vertigo, balance disorders)

Timing:

• Neuropsychiatric symptoms can occur after first dose or even weeks after discontinuation

• Halofantrine: Contraindicated; may cause serious QT prolongation and fatal arrhythmias
• Ketoconazole: Increases mefloquine levels due to CYP3A4 inhibition
• Anticonvulsants (e.g., valproate, phenytoin): Reduced efficacy; monitor seizure control
• Other QT-prolonging drugs: Additive cardiac risk; avoid combinations
• Rifampin: May decrease mefloquine plasma levels due to enzyme induction

Metabolism Note: CYP3A4 is the primary enzyme responsible for metabolism

• WHO Guidelines: Still considered an effective prophylactic in areas with chloroquine resistance, except in areas with known mefloquine resistance (e.g., parts of Southeast Asia)
• CDC Travel Guidelines: Recommends mefloquine for long-term travelers and military personnel, especially where weekly dosing is preferred
• Safety Monitoring: Updated product labeling includes stronger warnings on persistent neuropsychiatric side effects

• Temperature: Store below 30°C (86°F)
• Humidity/Light: Protect from excessive moisture and direct sunlight
• Handling Precautions: Keep in original packaging until use
• Reconstitution/Refrigeration: Not required; tablets are stable at room temperature