Mefloquine (Lariam) is an antimalarial drug that is used in the treatment and prevention of uncomplicated malaria. It may be used in the prophylaxis of chloroquine-resistant strains of plasmodium falciparum infections.

Mefloquine (Lariam) Uses:

• Acute malaria infections:

  • It is used in the treatment of mild to moderate acute malaria caused by mefloquine susceptible strains of Plasmodium falciparum. it can also be used in both chloroquine-susceptible and -resistant strains or by Plasmodium vivax.

• Prophylaxis of malaria:

  • It is also used in the prophylaxis of P. falciparum and P. vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum.

Note: CDC guidelines should be consulted for prophylaxis as they differ from region to region.

• Off Label Use f Mefloquine in Adults:

  • It is also used in the treatment of uncomplicated, chloroquine-resistant P. vivax malaria

Mefloquine (Lariam) Dose in Adults:

Mefloquine (Lariam) Dose in the treatment of Malaria: Oral (dose expressed as mg of mefloquine hydrochloride):

• Mild-to-moderately severe malaria:

  • 1,250 mg (5 tablets of 250 mg each) as a single dose. It is notable that If clinical improvement is not seen within 48 to 72 hours, alternative therapy should be used for re-treatment.

• Treatment of Uncomplicated malaria (off-label dose):

  • 750 mg (3 tablets of 250 mg each) as an initial dose, followed 6 to 12 hours later by 500 mg (2 tablets of 250 mg each).

• Treatment of uncomplicated, chloroquine-resistant P. vivax malaria (off-label):

  • 750 mg (3 tablets of 250 mg each) as an initial dose, followed 6 to 12 hours later by 500 mg (2 tablets of 250 mg each) followed by primaquine.

• Chemoprophylaxis:

  • It is given as 250 mg weekly starting 1 week (CDC 2014: ≥2 weeks) before arrival in an endemic area, continuing weekly during travel, and for 4 weeks after leaving an endemic area.
  • Prophylaxis should be started 2-3 weeks before to ensure tolerance.

Mefloquine (Lariam) Dose in Childrens:

Note: Dose is expressed in terms of the salt, mefloquine hydrochloride. Due to geographical resistance and cross-resistance, consult current CDC or WHO guidelines as appropriate.

Mefloquine (Lariam) Dose in the treatment of Malaria, treatment; chloroquine-resistant (independent of HIV status):

It is notable that therapy is recommended as a last-line option due to the higher rate of severe neuropsychiatric reactions. Other regimens should be considered first:

• CDC Guidelines:

  • Infants, Children, and Adolescents:
    • Orally it is given as 15 mg/kg once with a maximum dose of  750 mg/dose) followed in 6 to 12 hours with 10 mg/kg once with a maximum dose of 500 mg/dose).
    • It can also be used in combination with other antimalarial agents and local guidelines should be consulted. If clinical improvement is not seen within 48 to 72 hours, alternative therapy should be considered for retreatment

Mefloquine (Lariam) Dose in the chemoprophylaxis of malaria; (independent of HIV status):

Note: it should Begin 2 weeks before arrival in an endemic area, and be administered on the same day each week, and continue weekly during travel and for 4 weeks after leaving the endemic area.

• Infants, Children, and Adolescents:

  • Weight-based dosing:

    • Oral: 5 mg/kg/dose once a week and the maximum dose is 250 mg/dose.

  • Fixed dosing: Oral:

    • >9 to 19 kg:
      • 62.5 mg (1/4 of 250 mg tablet) once a week
    • >19 to 30 kg:
      • 125 mg (1/2 of 250 mg tablet) once a week
    • >30 to 45 kg:
      • 187.5 mg (3/4 of a 250 mg tablet) once a week
    • >45 kg:
      • 250 mg once a week

Pregnancy Risk Factor B

• Mefloquine crosses the placenta. Clinical experience with mefloquine in pregnancy has not shown any increased risk for adverse effects.
• Pregnant women could be at greater risk of developing malaria infection than non-pregnant women. This can lead to adverse pregnancy outcomes.
• The CDC has published guidelines for mefloquine use in treating malaria during pregnancy.
• Women of childbearing potential who are not pregnant should use contraception. They should also avoid pregnancy during mefloquine treatment and for the next 3 months.

Mefloquine use during breastfeeding:

• Breastmilk is now known to contain mefloquine at a rate of 3-4 percent from 250mg.
• Manufacturer recommends caution when giving mefloquine for breastfeeding mothers.
• Infants are safe to be exposed to small amounts of mefloquine in breast milk.

Dose in Kidney Disease:

No dosage adjustment necessary because only a small amount of mefloquine is renally excreted.

Dose in Liver disease:

• There are no dosage adjustments provided by the manufacturer.
• But, the half-life may be prolonged and plasma levels may be higher in patients with hepatic impairment.

Common Side Effects of Mefloquine (Lariam):

• Central nervous system:

  • Abnormal dreams
  • Insomnia

Less Common Side Effects of Mefloquine (Lariam):

• Gastrointestinal:

  • Vomiting

Contraindications to Mefloquine (Lariam):

• Hypersensitivity to mefloquine, or related compounds such as quinine or quinidine, is a serious contraindication.
• Patients with a history or current history of seizures or psychiatric disorder (including depression, generalized anxiety disorder or psychosis) are not advised to use it as Prophylaxis.
• It is not known if quinine derivatives have been shown to cause cross-reactivity. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Agranulocytosis, aplastic anemia

  • Reports of anemia and leucopenia are common.

• Modified cardiac conduction

  • Mefloquine can cause changes in the ECG, including sinus bradycardia and sinus arrhythmia.
  • Halofantrine, quinine, and quinidine which are QTc interval prolonging drugs should not be given concomitantly with mefloquine.

• Hypersensitivity reactions

  • Hypersensitivity reactions are common.

• Neuropsychiatric effects: [US Boxed Warn]

  • Due to its long half-life, mefloquine can cause neuropsychiatric adverse reactions that may persist. 
  • If symptoms develop, discontinue prophylactic mefloquine and seek out an alternative.
  • Early symptoms may appear during therapy. 
  • These symptoms can be difficult to identify in children and infants so it is important to monitor pediatric patients.
  • Paranoia, depression and anxiety are all possible symptoms of psychosis.
  • It has been reported that there are suicidal tendencies.
  • You may also experience vertigo-like symptoms, such as dizziness and tinnitus.
  • Mefloquine can be used to treat psychiatric comorbidities.
  • Be cautious when performing activities that require alertness and fine motor coordination (eg driving, piloting aircrafts, operating machinery), if you have neurologic symptoms.

• Cardiovascular disease

  • It can cause sinus bradycardia or arrhythmias and QT interval prolongation. These conditions can be fatal.

• Hepatic impairment

  • Patients with hepatic diseases should exercise caution as the drug is metabolized in their livers.

• Neuropsychiatric disorders [US Boxed Warning]

  • Patients with major psychiatric disorders, including active depression, psychosis, generalized anxiety disorder, and schizophrenia, should not be prescribed prophylaxis.
  • These patients should not be treated with any medication.
  • History of depression should not be considered.

• Ocular effects

  • During treatment, eye disorders such as optic neuropathy or retinal disorders were observed.
  • If you experience visual symptoms during treatment, an immediate ophthalmologic exam is required and the therapy may need to be stopped.

• Plasmodium falciparum infection:

  • Use only in cases of serious or life-threatening malaria infection caused by Plasmodium falciparum. To complete the treatment, you can give mefloquine orally.

• Plasmodium virex infections:

  • Use of the appropriate medication: If acute Plasmodium vires infection is treated with mefloquine then patients should be treated with an 8 aminoquinoline derivative (eg primaquine) in order to prevent relapse.

• Seizure disorder:

  • Patients with a history or seizures should be cautious when using this medication for treatment.
  • It may increase the chance of seizures. Patients with seizure disorders should not be prescribed prophylactically.

Mefloquine: Drug Interaction

Monitoring parameters:

When use is prolonged time, the following should be monitored.

• Periodic liver function tests.
• Evaluations for neuropsychiatric effects.
• ocular examinations

How to administer Mefloquine (Lariam)?

• Administer with food and with at least 240 mL of water.
• When used for malaria prophylaxis, the dose should be taken once weekly on the same day each week.
• If vomiting occurs within 30 minutes after the dose, an additional full dose should be given, if it occurs within 30 to 60 minutes after the dose, an additional half-dose should be given.
• Tablets may be crushed and suspended in a small amount of water, milk, or another beverage for persons unable to swallow tablets.

Mechanism of action of Mefloquine (Lariam):

• Mefloquine, a quinoline-methanol combination structurally similar to quinine, is also known as Mefloquine.
• Mefloquine is effective in treating and prophylaxis malaria.
• It destroys the asexual blood forms that malarial pathogens, such as Plasmodium falciparum and P. viridax.

Absorption:

• It is easily absorbed, and there is little interpatient variability in the rate.
• Suspension has a greater absorption rate than tablets.

Distribution: Distributes into tissues, erythrocytes, blood, urine, CSF Protein binding:

• ~98%

Metabolism:

• Extensively hepatic primarily by CYP3A4 to 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid (inactive) and other metabolites

Bioavailability:

• Increased by food

Half-life elimination:

• Children 4 to 10 years: Mean range: 11.6 to 13.6 days (range: 6.5 to 33 days);
• Adults: ~3 weeks (range: 2 to 4 weeks).
• It may be decreased during infection (2 weeks)

Time to peak, plasma:

• About 17 hours (range: 6 to 24 hours)

Excretion:

• Primarily bile and feces;
• urine (9% of total dose as unchanged drug, 4% of total dose as primary metabolite)

International Brand Names of Mefloquine:

• Eloquine
• Lariam
• Laricam
• Larimef
• Malariquin
• Malarium
• Malarivent T
• Mefliam
• Meflon
• Melophar
• Mephaquin
• Mequin
• Suton
• Tropicur
• Vexam

Mefloquine Brand Names in Pakistan: