Indications

Mefloquine is used for the treatment and prevention of malaria caused by susceptible P. falciparum include chloroquine resistant strains of P.falciparum.

Present

Blister of 10 tablets. Box of 1 blister.

Composition

Mefloquine hydrochloride ……………………………….250mg
Excipients s.q. for ………………………………………….1 tablet
(Lactose, croscarmellose sodium, povidone, magnesium stearate, microcrystalline cellulose, corn starch, hypromellose, titanium dioxide, talc, polyethylene glycol 6000, polysorbate 80, ethanol 96%).

Pharmacology

Mefloquine is a blood schizontocidal agent active against asexual erythrocytic forms of most strains of P. falciparum, P. vivax, P. malariae, P. ovale. Mefloquine is not active against mature gametocytes or against intrahepatic stages of plasmodial development.
Mefloquine is effective against all forms of malaria include multidrug– resistant such as chloroquine– , proguanil– , pyrimethamine– and fixed– combination– containing– pyrimethamine– resistant strains of P. falciparum.

Pharmacokinetics

Mefloquine is well absorbed from GI tract. Peak mefloquine concentrations in plasma averaged 0.2 – 1.4 microgam/mL are attained within 2 – 12 hours following administration of single oral mefloquine dose of 250mg. The minimum inhibitory concentration of mefloquine against P. falciparum are 0.2 – 0.3 microgam/mL. An absorption half– life of 0.36 – 2 hours has been reported, subtherapeutic concentrations of mefloquine may persist in the blood for several months. Mefloquine appears to concentrate in erythrocytes, the concentration is twice that in plasma. Mefloquine ismetabolized in the liver. The major metabolite (the quinoline carboxylic acid derivative) of mefloquine appears to be inactive against P. falciparum. The mean elimination half– life is about 3 weeks (ranging from 10 to 33 days). Mefloquine and its metabolites are excreted mainly in the bile and feces. Only 13% of the dose is excreted in the urine as unchanged parent compound or its carboxylic acid derivative.

Contra-Indications

– Mefloquine is contraindicated in individuals who are hypersensitive to any
component in the formulation or to the drugs with similar chemical structure such as chloroquine, quinine, quinidine.
– Patients with history of psychosis, epilepsy.
– Patients with severe hepatic or renal impairment.
– Patients with first or second degree AV heart block.

Side effect

– Dizziness, headache usually are transient in patients receiving mefloquine for the treatment of malaria, resolving within 24 hours in most patients and within 72 hours in all patients.
– Common: dizziness, headache, somnolence, insomnia, loss of balance, nausea, vomiting, diarrhea, abdominal pain.
– Less common: malaise, anorexia, fatigue, fever, chills, leukocytosis, leukocytopenia, thrombocytopenia, hypotension, hypertension, facial flushing,syncope, tachycardia, brachycardia, arrhythmia, extrasystoles, skin reaction, exanthema, erythema, urticaria, pruritus, alopecia, muscle weakness, muscle cramps, myalgia, arthralgia, neuropsychiatric reactions, paresthesia, spasms, agitation or restlessness, depression, forgetfulness, confusion, hallucinations, psychotic or paranoid reactions, visual disturbances and tinnitus.
– Rare: AV block, encephalopathy, transient elevations in transaminase values, Stevens– Johnson syndrome, erythema multiforme.
– Inform your doctor about side– effects when using this medicine.

Precaution

– Caution should be advised with regard to driving, operating machines since dizziness, a loss of balance and other central or peripheral nervous system effects have occurred during or 2 – 3 weeks following discontinuance of mefloquine administration.
– If neuropsychiatric manifestations such as anxiety, depression, restlessness or confusion occurring in patients receiving mefloquine prophylaxis the drug should be discontinued.
– Mefloquine should only be used in patients with neuropsychiatric disorder when clearly needed.
– Mefloquine should not be used longer than 1 year. If prolonged therapy is needed, periodical liver function tests, ophthalmological examinations should be performed (because the drug may impair liver functions and cause severe ocular damages).
PREGNANCY AND LACTATION:
– Pregnancy:
* Mefloquine should not be used for prophylaxis of malaria during pregnancy. In the first trimester of pregnancy, use only when clearly needed.
* Women of childbearing potential should be advised to use effective contraceptive measures while receiving mefloquine prophylaxis and for up to 3 months following the last mefloquine dose.
– Lactation: safety and efficacy of mefloquine in children under 6 months of age is not established. Mefloquine is distributed into breast milk, because the amount of mefloquine consumed by a nursing infant is likely to be small, the risk to nursing infants of maternal use is thought to be low. However, mefloquine concentrations in breast milk may be higher in nursing women, who received prolonged mefloquine treatment or prophylaxis, since its elimination half– life is quite long. Discontinue nursing or the drug.

Interaction

– There is a report of cardiac arrest in a patient who had taken only one dose of mefloquine while on propanolol.
– Use with extreme cautions in patients who are on beta– blockers, calcium channel blockers, digitalis or antidepressive agents.
– Concomitant use of mefloquine with other related drugs such as quinine, quinidine, chloroquine may result in ECG abnormalities.
– Combination with primaquine may increase side– effects rate caused by mefloquine.
– Coadminister with valproic acid may decrease the latter serum valproate concentration.
– If quinine, quinidine, chloroquine is used in the initial treatment of severe malaria, mefloquine should not be administered until at least 12 hours after the last dose of any of these drugs.
OVERDOSAGE & MANAGEMENT:
– Overdosage of mefloquine would be expected to produce manifestation that are principally extensions of the adverse reactions reported with the drug. Mefloquine overdose may cause liver, heart or neuropathy manifestations in patients who ingested an overdosage of mefloquine (up to 5.25g over 6 days). Neuropsychiatric side effects generally resolve within a few days after withdrawal of mefloquine and with supportive pharmacotherapy, but occasionally symptoms persist for several weeks.
– If acute mefloquine overdosage occurs, supportive and symptomatic treatment should be initiated and the patients observed closely. If indicated the stomach may be emptied by inducing emesis or gastric lavage, hepatic and cardiac function and neurologic and psychiatric status should be monitored for at least 24 hours. Appropriate fluid and electrolyte replacement should be used for vomiting and diarrhea.
– Should overdosage occur, turn to the nearest healthcare facility for medical attention of the healthcare professionals.

Shelf life

36 months from the manufacturing date.

Storage

Store in a dry place, protect from light, not exceeding 30^oC.

Dosage

– Mefloquine should be administered with food and with plenty of water.
– As prescribed by the physician.
– Recommended dosage:
* Treatment of malaria:
. Adults: 15mg/kg, up to of 1000mg in 2 divided doses, given 6 – 8 hours apart.
. Children: 15mg/kg in 2 divided doses, given 6 – 8 hours apart.
Note: mefloquine should not be used in children who weigh less than 15kg or younger than 2 years of age.
* Prevention of malaria in individuals travelling to high– risk malarious area in a short time.
. Adults: 1 tablet once daily for 3 consecutive day of the first week of therapy, followed by 1 tablet once weekly.
. Children: 15mg/kg for 3 consecutive day of the first week of therapy, followed by:
+ 3 – 23 months of age: 1/4 tablet once weekly.
+ 2 – 7 years of age: 1/2 tablet once weekly.
+ 8 – 13 years of age: 3/4 tablet once weekly.
+ ≥ 14 years of age: 1 tablet once weekly.
Administration should be continued for 4 weeks after leaving the malarious area.
Note: mefloquine should not be used in children younger than 3 months of age.