Mefloquine

Prophylaxis or Treatment of Malaria
1. Preferred Malaria Prophylaxis agent in Chloroquine resistance areas (esp. longterm travel >6 months)
2. Less commonly used for Malaria treatment

Developed in the 1970s at Walter Reed Army Institute of Research (WRAIR) as an alternative to Chloroquine
Structural analog of Quinine
1. Quinoline ring with Methanol group
Mefloquine is active during the erythrocytic stage of Malaria (but not the hepatic stage)
1. Mefloquine concentrates in erythrocytes (within parasitic vacuoles)
2. Mefloquine inhibits heme detoxification by Parasites

Mefloquine Tablets: 250 mg
1. Take with food and full 8 oz glass of water
2. Tablets may be crushed and mixed with a small amount of water, milk or other liquids

Protocol
1. Start dosing 1 week before exposure
2. Complete dosing 4 weeks after exposure
Adult
1. Mefloquine 250 mg salt (228 mg base) orally once weekly
Child
1. Weight <9 kg
  1. Mefloquine 5 mg/kg salt (4.6 mg/kg base) orally once weekly
2. Weight 9 to 19 kg
  1. Mefloquine 1/4 of adult tablet orally once per week
3. Weight: 20 to 30 kg
  1. Mefloquine 1/2 of adult tablet orally once per week
4. Weight: 31 to 45 kg
  1. Mefloquine 3/4 of adult tablet orally once per week
5. Weight: >45 kg
  1. Mefloquine 1 adult tablet (250 mg) orally once per week

Adult
1. Dose 1: Mefloquine 750 mg salt (684 mg base)
2. Dose 2: Mefloquine 500 mg salt (456 mg base) in 8 to 12 hours after first dose
Child
1. Dose 1: Mefloquine 15 mg/kg salt (13.7 mg/kg base)
2. Dose 2: Mefloquine 10 mg/kg salt (9.1 mg/kg base) in 8 to 12 hours after first dose

Half-Life: 33 days
Peak Effect (oral): 6-24 hours
Steady state reached
1. Weekly dose: 7 weeks
2. Loading dose: 4 days
Metabolism: CYP3A4
Distribution
1. Highly lipophilic (results in a very long half life)
2. Highly Protein bound
3. Large volume of distribution
4. Easily crosses blood brain barrier with risks of neurotoxicity in Overdose

Vestibular toxicity
1. Risk of longterm Vertigo and Tinnitus
Arrhythmia in patients with cardiac conduction defect
1. QT Prolongation
2. Sinus Bradycardia
Neuropsychological effects (uncommon 1:200 to 1:500, but is a FDA black box warning)
1. Insomnia
2. Nightmares
3. Anxiety
4. Irritability
5. Drowsiness
6. Dizziness or Vertigo
7. Tinnitus
8. Headache
9. Major Depression
  1. Possible increased Suicidality
10. Psychosis (paranoia, Hallucinations) or Seizures (rare)
  1. Prophylaxis Incidence: <1:10,000
  2. Treatment Incidence: 1:100 to 1:1500

Gastrointestinal
Endocrine
1. Hypoglycemia (high Insulin levels)
Cardiovascular
1. Bradycardia
2. QT Prolongation
Neurotoxicity
1. See adverse effects at standard doses above
2. Seizures
3. Encephalopathy
4. Hyperactive Delirium
Management of Overdose
1. See Unknown Ingestion
2. Oral Activated Charcoal if ingestion in last 1-2 hours (airway precautions)
3. Hypoglycemia
  1. See Hypoglycemia Management
  2. IV Dextrose
4. Seizures
  1. See Status Epilepticus
  2. Benzodiazepines
5. Anticholinergic Toxicity with Antimuscarinic Poisoning effects
  1. See Anticholinergic Toxicity
  2. Consider Physostigmine
6. Disposition
  1. Admit all symptomatic Overdoses
  2. Observe asymptomatic Overdoses for neurotoxicity for 24 hours
References
1. Carroll and Yakey (2025) Crit Dec Emerg Med 39(8): 42

Considered safe in Lactation
1. However, infant is not protected from Malaria by Breast Feeding (minimal medication in Breast Milk)
Pregnancy Category B
1. No significant adverse fetal affects in studies (any trimester)