MEFLINE 250MG TABLET

Indications

• Treatment of malaria
• Prophylaxis of malaria

Dosage

Children: For children, dosing varies by body weight: 62.5 mg once weekly for 5-15 kg, 125 mg for 16-24 kg, 187.5 mg for 25-44 kg, and 250 mg for 45 kg and above, starting 2-3 weeks before entering an endemic area and continuing

Adults: For adults, 250 mg once weekly for prophylaxis, starting 2-3 weeks before entering an endemic area and continuing for 4 weeks after leaving.

Mechanism of action

Mefloquine's mechanism of action is not completely understood but is believed to involve inhibition of protein synthesis in the Plasmodium falciparum by targeting the 80S ribosome. It interferes with the parasite's ability to metabolize hemoglobin, leading to schizonticidal effects. Additionally, mefloquine may inhibit calcium release in certain cellular contexts, which contributes to its antimalarial activity.

Pharmacodynamics

Mefloquine acts as a blood schizonticide, targeting the intraerythrocytic stages of malaria parasites. It prevents the maturation of parasites within red blood cells, thereby reducing the severity of malaria. The drug's effectiveness is evident in reducing the parasitemia associated with malaria infection.

Pharmacokinetics

Mefloquine is well-absorbed after oral administration, with peak plasma concentrations achieved within 24 hours. It has a long half-life, allowing for once-weekly dosing in prophylaxis. The drug is extensively metabolized in the liver, with only a small portion excreted unchanged in urine. Caution is advised in patients with hepatic or renal impairment, though dose adjustments are typically unnecessary for prophylaxis in mild to moderate cases.

Contra-indications

• History of psychiatric disorders (including depression)
• History of convulsions
• History of blackwater fever

Adverse effects

• Anxiety
• Depression
• Insomnia
• Abnormal dreams
• Psychosis
• Suicidal ideation
• Dizziness
• Nausea
• Headache
• Gastrointestinal discomfort
• Arrhythmias
• Mood alterations
• Memory loss
• Hearing impairment
• Visual disturbances

Interactions

• Increased exposure with ketoconazole
• Increased exposure with fluconazole
• Increased exposure with itraconazole
• Increased exposure with voriconazole
• Increased risk of bradycardia with non-selective beta-blockers
• Increased risk of bradycardia with selective beta-blockers
• Increased risk of bradycardia with calcium channel blockers
• Increased risk of bradycardia with digoxin
• Decreased exposure with rifampicin

Precautions

• Caution in hepatic impairment, especially in cirrhosis
• Caution in renal impairment, as only partially excreted by the kidneys
• Long-term use may necessitate regular ophthalmic examinations

Pregnancy

Use in pregnancy should be avoided if the disease is well controlled.

Breast-feeding

Present in breast milk; breastfeeding should be avoided when used to treat rheumatic disease. Amount in milk probably too small to be harmful when used for malaria.

Storage

Store below 25°C, protected from light.

Formulations

• Mefloquine tablets
• Malarivon syrup (80mg/5ml)

Mechanism of action

The mechanism of action of mefloquine is not completely understood. Some studies suggest that mefloquine specifically targets the 80S ribosome of the Plasmodium falciparum, inhibiting protein synthesis and causing subsequent schizonticidal effects. There are other studies in the literature with limited in vitro data on mefloquine's mechanism of action. Mefloquine, like chloroquine and quinine, is a blood schizonticidal agent and is active against the intraerythrocytic stages of parasite development. Similar to chloroquine and quinine, mefloquine appears to interfere with the parasite's ability to metabolize and utilize erythrocyte hemoglobin. The antimalarial activity of mefloquine may depend on the ability of the drug to form hydrogen bonds with cellular constituents; results of structure-activity studies indicate that the orientation of the hydroxyl and amine groups with respect to each other in the mefloquine molecule may be essential for antimalarial activity. While the precise mechanism of action of mefloquine is unknown, it may involve mechanisms that differ from those proposed for chloroquine. The effects of the antimalarial drug, mefloquine, on the uptake and release of Ca2+ by crude microsomes from dog brain were investigated using a spectrophotometric method. Mefloquine inhibited the inositol-1,4,5-phosphate (IP3)-induced Ca2+ release with an IC50 of 42 uM, but was a weaker inhibitor of the uptake of Ca2+ into the vesicles (IC50: 272 uM). These effects of mefloquine are in contrast to its actions on Ca2+ uptake and release by skeletal muscle microsomes, where its predominant effect was seen to be the inhibition of Ca2+ uptake into the vesicles. Mefloquine was found to be more potent than quinine as a specific inhibitor of Ca2+ release from IP3-sensitive stores in dog brain microsomes. The possibility of the drug affecting cellular IP3-linked signal transduction processes should be considered.

Pharmacodynamics

Sporozoites located in the salivary glands of mosquitoes infected with malaria parasites are introduced into the bloodstream of a human host during mosquito feeding. These sporozoites rapidly invade the liver, where they mature into liver-stage schizonts, rupturing and releasing 2,000 - 40,000 merozoites that invade red blood cells. Mefloquine is an antimalarial drug acting as a blood schizonticide, preventing and treating malaria.