FDA

Mefloquine Hydrochloride

Approved 29 Dec 2003OralTablet

The FDA lists this product in 5 strengths and forms.

Indications

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). Prevention of Malaria Mefloquine hydrochloride tablets are indicated for the prophylaxis of P. falciparum and P. vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum.

Contraindications

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.

Warnings and precautions

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 (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Elimination ).

Ketoconazole 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. Ketoconazole increases plasma concentrations and elimination half-life of mefloquine following coadministration (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Elimination and PRECAUTIONS, Drug Interactions ). Concomitant administration of mefloquine and quinine or quinidine may produce electrocardiographic abnormalities.

At a glance

Brand name: Mefloquine Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Barr
Status: Prescription
FDA approval: 29 Dec 2003
Application: ANDA076392-001

Indications

Contraindications

Warnings and precautions

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.

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 (see WARNINGS ). 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 (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. Clinically significant QTc prolongation has not been found with mefloquine alone. Ketoconazole (Potent Inhibitor of CYP3A4) Coadministration of a single 500 mg oral dose of mefloquine with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in an increase in the mean C max and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours.

Ketoconazole 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 (see WARNINGS ). Other Drugs that Prolong the QTc Interval Coadministration of other drugs known to alter cardiac conduction (e.g., anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H 1 -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. Anticonvulsants In patients taking an anticonvulsant (e.g., 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 anti-seizure medication and mefloquine should have the blood level of their anti-seizure medication monitored and the dosage adjusted appropriately (see PRECAUTIONS ).

Vaccines 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. Rifampin (Potent Inducer of CYP3A4) Coadministration of a single 500 mg oral dose of mefloquine and 600 mg of rifampin once daily for 7 days in 7 healthy Thai volunteers resulted in a decrease in the mean C max and AUC of mefloquine by 19% and 68%, respectively, and a decrease in the mean elimination half-life of mefloquine from 305 hours to 113 hours.

Rifampin should be used cautiously in patients taking mefloquine. Inhibitors and Inducers of CYP3A4 Mefloquine does not inhibit or induce the CYP 450 enzyme system. Thus, concomitant administration of mefloquine hydrochloride tablets and substrates of the CYP 450 enzyme system is not expected to result in a drug interaction. However, mefloquine is metabolized by CYP3A4 and inhibitors of CYP3A4 may modify the pharmacokinetics/metabolism of mefloquine, leading to an increase in mefloquine plasma concentrations and potential risk of adverse reactions.

Therefore, mefloquine hydrochloride tablets should be used with caution when administered concomitantly with CYP3A4 inhibitors. Similarly, inducers of CYP3A4 may modify the pharmacokinetics/metabolism of mefloquine, leading to a decrease in mefloquine plasma concentrations and potential reduction in efficacy of mefloquine hydrochloride tablets. Therefore, mefloquine hydrochloride tablets should also be used with caution when administered concomitantly with CYP3A4 inducers.

Substrates and Inhibitors of P-glycoprotein It has been shown in vitro that mefloquine is a substrate and an inhibitor of P-glycoprotein. Therefore, drug-drug interactions could also occur with drugs that are substrates or are known to modify the expression of this transporter. The clinical relevance of these interactions is not known to date. Other Potential Interactions No other drug interactions are known. Nevertheless, the effects of mefloquine on travelers receiving concomitant medications, 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 of mefloquine.

Adverse reactions

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 (see PRECAUTIONS, Drug Interactions ), and encephalopathy of unknown etiology during prophylactic mefloquine administration. The relationship of encephalopathy to drug administration could not be clearly established. Among subjects who received mefloquine for treatment, the most frequently observed adverse experiences included: dizziness, myalgia, nausea, fever, headache, vomiting, chills, diarrhea, skin rash, abdominal pain, fatigue, loss of appetite, and tinnitus.

Those side effects occurring in less than 1% included bradycardia, hair loss, emotional problems, pruritus, asthenia, transient emotional disturbances and telogen effluvium (loss of resting hair). Seizures have also been reported. Laboratory The most frequently observed laboratory alterations which could be possibly attributable to drug administration were decreased hematocrit, transient elevation of transaminases, leukopenia and thrombocytopenia.

These alterations were observed in patients with acute malaria who received treatment doses of the drug and were attributed to the disease itself. During prophylactic administration of mefloquine to indigenous populations in malaria-endemic areas, the following alterations in laboratory values were observed: transient elevation of transaminases, leukocytosis or thrombocytopenia. Because of the long half-life of mefloquine, adverse reactions to mefloquine may occur or persist up to several weeks after discontinuation of the drug.

Postmarketing Postmarketing surveillance indicates that the same kind of adverse reactions are reported during prophylaxis, as well as acute treatment. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to mefloquine exposure. The most frequently reported adverse reactions are nausea, vomiting, loose stools or diarrhea, abdominal pain, dizziness or vertigo, loss of balance, and neuropsychiatric events such as headache, somnolence, and sleep disorders (insomnia, abnormal dreams).

These adverse reactions may occur early in the course of mefloquine use. It has been reported that dizziness or vertigo, tinnitus and hearing impairment, and loss of balance may continue for months or years after discontinuation of the drug and may be permanent in some cases. More severe neuropsychiatric disorders have been reported such as: sensory and motor neuropathies (including paresthesia, tremor and ataxia), convulsions, agitation or restlessness, anxiety, depression, mood swings, panic attacks, memory impairment, confusion, hallucinations, aggression, psychotic or paranoid reactions and encephalopathy.

Cases of suicidal ideation and suicide have been reported. Other less frequently reported adverse reactions include: Cardiovascular Disorders: circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitation, bradycardia, irregular heart rate, extrasystoles, A-V block, and other transient cardiac conduction alterations. Skin Disorders: rash, exanthema, erythema, urticaria, pruritus, edema, hair loss, erythema multiforme, and Stevens-Johnson syndrome.

Musculoskeletal Disorders: muscle weakness, muscle cramps, myalgia, and arthralgia. Respiratory Disorders: dyspnea, pneumonitis of possible allergic etiology. Hepatobiliary Disorders: drug-related hepatic disorders from asymptomatic transient transaminase elevations to hepatic failure. Blood and Lymphatic System Disorders: agranulocytosis, aplastic anemia. Ocular Disorders: visual impairment, vision blurred, cataracts, retinal disorders, optic neuropathy.

Other Symptoms: asthenia, malaise, fatigue, fever, hyperhidrosis, chills, dyspepsia and loss of appetite. To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Mefloquine Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Mefloquine Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information