Mefloquine (Mefloquine Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

10-2008M

7271

Sandoz Inc.

Princeton, NJ 08540

DRUG INTERACTIONS

Drug Interactions

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) (see PRECAUTIONS: Cardiac Effects). 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.

Because of the danger of a potentially fatal prolongation of the QTc interval, halofantrine must not be given simultaneously with or subsequent to mefloquine (see WARNINGS).

Concomitant administration of mefloquine and other related compounds (eg, quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions (see WARNINGS). If these drugs are to be used in the initial treatment of severe malaria, mefloquine administration should be delayed at least 12 hours after the last dose. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Clinically significant QTc prolongation has not been found with mefloquine alone.

This appears to be the only clinically relevant interaction of this kind with mefloquine, although theoretically, coadministration of other drugs known to alter cardiac conduction (eg, anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H₁-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. There are no data that conclusively establish whether the concomitant administration of mefloquine and the above listed agents has an effect on cardiac function.

In patients taking an anticonvulsant (eg, valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of mefloquine may reduce seizure control by lowering the plasma levels of the anticonvulsant. Therefore, patients concurrently taking antiseizure medication and mefloquine should have the blood level of their antiseizure medication monitored and the dosage adjusted appropriately (see PRECAUTIONS).

When mefloquine is taken concurrently with oral live typhoid vaccines, attenuation of immunization cannot be excluded. Vaccinations with attenuated live bacteria should therefore be completed at least 3 days before the first dose of mefloquine hydrochloride tablets.

No other drug interactions are known. Nevertheless, the effects of mefloquine on travelers receiving comedication, particularly diabetics or patients using anticoagulants, should be checked before departure.

In clinical trials, the concomitant administration of sulfadoxine and pyrimethamine did not alter the adverse reaction profile.

OVERDOSAGE

Symptoms and Signs

In cases of overdosage with mefloquine, the symptoms mentioned under ADVERSE REACTIONS may be more pronounced.

Treatment

Patients should be managed by symptomatic and supportive care following mefloquine overdose. There are no specific antidotes. Monitor cardiac function (if possible by ECG) and neuropsychiatric status for at least 24 hours. Provide symptomatic and intensive supportive treatment as required, particularly for cardiovascular disturbances.

CONTRAINDICATIONS

Use of mefloquine hydrochloride tablets is contraindicated in patients with a known hypersensitivity to mefloquine or related compounds (eg, 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, or schizophrenia or other major psychiatric disorders, or with a history of convulsions.