Mefloquine

Treatment of Acute Malaria Infections Mefloquine hydrochloride tablets are 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. There are insufficient clinical data to document the effect of mefloquine in malaria caused by P. ovale or P. malariae. Note: 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 (e.g., primaquine).

Mefloquine is an antimalarial agent which acts as a blood schizonticide. Its exact mechanism of action is not known. Activity In Vitro and In Vivo: Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Drug Resistance: Strains of P. falciparum with decreased susceptibility to mefloquine can be selected in vitro or in vivo. Resistance of P. falciparum to mefloquine has been reported in areas of multi-drug resistance in South East Asia. Increased incidences of resistance have also been reported in other parts of the world. Cross-Resistance: Cross-resistance between mefloquine and halofantrine and cross-resistance between mefloquine and quinine have been observed in some regions.

Malaria Treatment in Adults Treatment of mild to moderate malaria in adults caused by mefloquine-susceptible strains of P. falciparum or by P. vivax: Dosage: Five tablets (1250 mg) mefloquine hydrochloride to be given as a single oral dose. The drug should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water. If a full-treatment course with mefloquine does not lead to improvement within 48 to 72 hours, 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. Note: Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites.

Use of mefloquine hydrochloride tablets is contraindicated in patients with a known hypersensitivity to mefloquine or related compounds (e.g., quinine and quinidine) or to any of the excipients contained in the formulation. Mefloquine hydrochloride tablets should not be prescribed for prophylaxis in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia or other major psychiatric disorders, or with a history of convulsions.

WARNING Mefloquine may cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued. Mefloquine 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. In case of life-threatening, serious or overwhelming malaria infections due to P. falciparum, patients should be treated with an intravenous antimalarial drug. Following completion of intravenous treatment, mefloquine may be given to complete the course of therapy. QTc Interval Prolongation and Drug Interactions Halofantrine should not be administered with mefloquine or within 15 weeks of the last dose of mefloquine due to the risk of a potentially fatal prolongation of the QTc interval.

Clinical At the doses used for treatment of acute malaria infections, the symptoms possibly attributable to drug administration cannot be distinguished from those symptoms usually attributable to the disease itself. Among subjects who received mefloquine for prophylaxis of malaria, the most frequently observed adverse experience was vomiting (3%). Dizziness, syncope, extrasystoles and other complaints affecting less than 1% were also reported. Two serious adverse reactions were cardiopulmonary arrest in one patient shortly after ingesting a single prophylactic dose of mefloquine while concomitantly using propranolol, and encephalopathy of unknown etiology during prophylactic mefloquine administration. The relationship of encephalopathy to drug administration could not be clearly established.

Drug-drug interactions with mefloquine have not been explored in detail. There is one report of cardiopulmonary arrest, with full recovery, in a patient who was taking a beta blocker (propranolol). The effects of mefloquine on the compromised cardiovascular system have not been evaluated. The benefits of mefloquine therapy should be weighed against the possibility of adverse effects in patients with cardiac disease. Halofantrine Halofantrine should not be administered with mefloquine or within 15 weeks of the last dose of mefloquine due to the risk of a potentially fatal prolongation of the QTc interval. Other Antimalarial Drugs Concomitant administration of mefloquine and other related antimalarial compounds (e.g., quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions.

Store at 20° to 25°C (68° to 77°F).