Mefloquine 250 mg

Bioavailability of mefloquine increases by 40% when taken with food.

There are no specific recommendations for dose adjustments in patients with hepatic dysfunction. Half-life may be prolonged and plasma levels increased.

Neither mefloquine or its major carboxylic metabolite are removed by hemodialysis, thus no dose adjustments are indicated.

Take as soon as the omission is recognized. Do not take a double dose.

abdominal pain, loss of appetite.

agranulocytosis, aplastic anemia, hemolytic anemia, leukocytosis, thrombocytopenia.

arthralgia, cramps, muscle weakness, myalgia.

hypoglycemia, increased insulin levels, abnormal thyroid function tests.

visual disturbances.

Incidence of serious neuropsychiatry events with prophylactic doses has been documented as 1:10 600. Incidence of seizures and psychosis with treatment doses has been documented as 1:100 to 1:1700.

Abnormal dreams, aggression, agitation and restlessness, anxiety, confusion, depression, emotional problems, fatigue, fever, hallucinations, headache, insomnia, mood changes, panic attacks, seizures, sensory and motor neuropathy (including paresthesias, tremor and ataxia), psychotic or paranoid reactions, suicidal ideation, syncope, tinnitus, vestibular disorders.

erythema multiforme, exanthema, hair loss, pruritus, sweating, Stevens-Johnson syndrome, urticaria.

A-V block, sinus bradycardia (may occur 4-7 days after mefloquine administration, may last 3-4 days), chest pain (rare), circulatory disturbances (flushing, hypertension, hypotension, syncope), extrasystole, irregular pulse, tachycardia, QTc prolongation.

It is recommended that a poison control centre be contacted to obtain expert advice on the management of mefloquine overdose.

General management of mefloquine overdose includes supportive care. Closely observe vital signs especially for hypotension and bradycardia. Monitor cardiac function, i.e. ideally by continuous rhythm monitoring or by serial electrocardiographs. Monitor neuropsychiatric status. For large overdoses of mefloquine, activated charcoal should be considered at a dose of 1 g/kg if it can be administered within 2 hours of ingestion. Mefloquine is not removed by hemodialysis and the drug undergoes enterohepatic recirculation.

In overdose, the adverse events of mefloquine are more pronounced. The drug has a long half-life so adverse reactions due to overdose may persist for several weeks after administration. Along with neuropsychiatric events reported in cases of mefloquine overdoses, QTc prolongation has also been reported.

Potentiation of postural hypotension and dizziness may occur with mefloquine use. Caution is advised.

WHO advises against the use of mefloquine chemoprophylaxis in individuals who require a high degree of manual dexterity, coordination and spatial discrimination for their occupations (e.g., pilots). However, a small study in trainee pilots using a flight simulator revealed no significant performance deficit. Some sleep disturbance and decreased concentration were noted.

Pregnancy Category C. Mefloquine readily crosses the placenta. Mefloquine is teratogenic in rats and mice at a dose of 100 mg/kg/day and in rabbits at a dose of 80 mg/kg/day. It has been used to treat P. falciparum malaria in pregnant women during the first, second and third trimesters of pregnancy. No increase in the rate of congenital abnormalities and no effects on physical and neurological development up to the age of 12 months have been reported. An increased incidence of stillbirth in women treated with mefloquine cannot be ruled out. Mefloquine is not associated with an increased incidence of teratogenic effects when given after the 1^st trimester. If travel to regions where chloroquine-resistant malaria is endemic cannot be avoided, the decision to use mefloquine during pregnancy should be based on whether the expected benefits of therapy justify the potential risk to the exposed fetus. Several studies in pregnant women have revealed no increase in the rate of fetal malformations.

Women of childbearing potential should be warned about the potential teratogenic properties of mefloquine (see Warnings and Precautions) and advised to practise contraception especially during and for 3 months after taking the last dose of mefloquine because of its long half-life. However, in the event that pregnancy occurs during prophylaxis with mefloquine, termination of pregnancy is not automatically indicated. Specialist consultation is recommended.

Mefloquine is secreted in human breast milk, however, the amount is not considered to be harmful to a nursing infant. WHO considers it to be safe in breastfeeding. Maternal use of mefloquine does not protect the nursing infant from malaria.

Mefloquine is a 4-quinoline-methanol antimalarial agent that is structurally related to quinine and quinidine. The exact mechanism of action of mefloquine is unknown; however, the drug is active against the erythrocytic stages of Plasmodium species, and inactive against the hepatic (exoerythrocytic) stages of the life cycle of these parasites. Mefloquine is active against malarial strains resistant to chloroquine; however, resistance to mefloquine, and cross resistance between mefloquine and halofantrine, and between mefloquine and quinine has been reported.

Data from clinical studies shows that mefloquine blood concentrations of 462, 620 and 915 ng/mL are associated with 90, 95 and 99% prophylactic efficacy.

Because acute malaria is associated with altered gastrointestinal motility, reduced visceral perfusion and impaired absorption, pharmacokinetics of mefloquine may be altered in patients with acute malaria. Further changes in clearance may occur due to impaired hepatic function and interruption in enterohepatic cycling of mefloquine may result in shorter terminal half-life.

Marked ethnic variation in the plasma concentrations of mefloquine has been reported. After administration of single 500 and 750 mg doses to healthy Asian adults, mean peak concentrations of mefloquine were 1010 and 1401 ng/mL, respectively (see Table 5 for comparison). The reason for the difference between Asian and non-Asian individuals is not known.

The pharmacokinetics of mefloquine have been studied in Thai children with uncomplicated P. falciparum malaria. In those aged 5 to 12 years, peak plasma concentrations of 3.7 to 3.9 µg/mL were reached in 6.6 to 7.4 hours after a single 20 mg/kg dose of a mefloquine oral suspension. In those aged 6 to 24 months a mean peak plasma concentration of 3.3 µg/mL was achieved 12.8 hours after administration of a 25 mg/kg single dose of a mefloquine oral suspension.

Summary of the pharmacokinetic properties of mefloquine after oral administration of a single dose in healthy adult volunteers^{a , b}