Dosing and uses of Mefloquine
Adult dosage forms and strengths
tablet
- 250mg
Acute Malaria Infections
Indicated for the treatment of mild-to-moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax
1250 mg PO once
Malaria Prevention
250 mg PO qWeek
Start 1-2 weeks before arrival in endemic area; continue 4 weeks after leaving endemic area
Dosing Considerations
If a full-treatment course does not lead to improvement within 48-72 hr, mefloquine should not be used for retreatment; an alternative therapy should be used
Similarly, if previous prophylaxis with mefloquine failed, mefloquine should not be used for curative treatment
Insufficient clinical data exist to document the effect of mefloquine in malaria caused by P. ovale or P. malariae
Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites; to avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (eg, primaquine)
Chloroquine-Resistant Malaria (Orphan)
Prevention and treatment of chloroquine-resistant Faciparum malaria
Orphan indication sponsor
- Mepha AG; 4143 Dornach; Postfash 137, Switzerland
Administration
Take with food and >8 oz water
May repeat full or partial dose if vomited
Pediatric dosage forms and strengths
tablet
- 250mg
Acute Malaria Infections
Indicated for the treatment of mild-to-moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax
<6 months old: Safety and efficacy not established
>6 months old: 20-25 mg/kg PO as single dose or may divide in 2 doses
Malaria Prevention
5 to <10 kg: 31.25 mg (1/8 tablet) PO qWeek
10 to <20 kg: 62.5 mg (1/4 tablet) PO qWeek
20 to <30 kg: 125 mg (1/2 tablet) PO qWeek
30-45 kg: 187.5 mg (3/4 tablet) PO qWeek
>45 kg: 250 mg (1 tablet) PO qWeek
Start 1-2 weeks before arrival in endemic area; continue 4 weeks after leaving endemic area
Dosing Considerations
If a full-treatment course does not lead to improvement within 48-72 hr, mefloquine should not be used for retreatment; an alternative therapy should be used
Similarly, if previous prophylaxis with mefloquine failed, mefloquine should not be used for curative treatment
Insufficient clinical data exist to document the effect of mefloquine in malaria caused by P. ovale or P. malariae
Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites; to avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (eg, primaquine)
Administration
Take with food and >8 oz water
May repeat full or partial dose if vomited
Mefloquine adverse (side) effects
1-10%
Anxiety
Difficulty concentrating
Headache
Insomnia
Lightheadedness
Vertigo
Vomiting
Diarrhea
Stomach pain
Nausea
Visual disturbances
Tinnitus
Frequency not defined
Suicidal depression
Psychiatric Sx
Pneumonitis
Seizure
Abnormal ECg
Warnings
Black box warnings
May cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued
Should not be prescribed for prophylaxis in patients with major psychiatric disorders
During prophylactic use, if psychiatric or neurologic symptoms occur, the drug should be discontinued and an alternative medication should be substituted
Contraindications
Hypersensitivity to mefloquine, related drugs (eg, quinidine, quinine)
Do not prescribe for prophylaxis in patients with active or recent history of depression, generalized anxiety disorder; history of psychosis, schizophrenia, other major psychiatric disorders, or convulsions
Cautions
In case of life-threatening, serious or overwhelming malaria infections due to P. falciparum, patients should be treated with an IV antimalarial drug; following completion of IV treatment, mefloquine may be given to complete the course of therapy
May increase QT interval; caution with other drugs known to prolong QT intervaL
Strong CYP3A4 inhibitors (eg, ketoconazole) should do not coadminister with or within 15 weeks after the last mefloquine dose
Caution with hepatic impairment
Agranulocytosis and aplastic anemia reported
Geographical drug resistance patterns of P. falciparum occur and the preferred choice of malaria prophylaxis might be different from one area to another
Periodic ophthalmic examinations recommended; retinal abnormalities seen in humans with long-term chloroquine use have not been observed with mefloquine use; however, long- term feeding of mefloquine to rats resulted in dose-related ocular lesions
Psychiatric and neurologic adverse effects
- May cause neuropsychiatric adverse reactions, which may be difficult to identify in children; monitor for symptoms, especially in nonverbal children
- Psychiatric symptoms ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior can occur; symptoms may occur early in the course of mefloquine use and in some cases, these symptoms have been reported to continue for months or years after mefloquine has been stopped
- Cases of suicidal ideation and suicide have been reported
- Should not be prescribed for prophylaxis in patients with active depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders
- Dizziness or vertigo, tinnitus, and loss of balance reported; these symptoms were reported to be permanent in some cases
- May increase the risk of convulsions in patients with epilepsy; prescribed only for curative treatment in such patients and only if there are compelling medical reasons for its use
- Concomitant administration of mefloquine and quinine or chloroquine may increase the risk of convulsions
- During prophylactic use, if symptoms emerge, discontinue and substitute treatment with a different antimalarial agent
Pregnancy and lactation
Pregnancy category: B
Lactation: Minimally excreted in human breast milk; based on a study in a few subjects, low concentrations (3% to 4%) excreted; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mefloquine
Mechanism of action
Structural analog of quinine; exact mechanism unknown, acts as a blood schizonticide
May increase intravesicular pH in parasites
Absorption
Bioavailability: Well absorbed; >85%; food enhances bioavailability by ~40%
Peak plasma time: 17 hr (range 6-24 hr)
Peak plasma concentration: 1000-2000 mcg/L (after 7-10 wk of 250 mg once weekly dosing)
Distribution
Vd: 20 L/kg; blood, urine, CSF, tissues; enters breast milk
Protein Bound: 98%
Metabolism
Extensively metabolized in liver by CYP3A4
Metabolites: 2,8-bistrifluoromethyl-4-quinoline carboxylic acid is inactive
Elimination
Half-life: 21-22 days
Total clearance (hepatic): 30 mL/min
Excretion: Mainly in bile and feces; urine (~1.5-9% as unchanged drug)
