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Mefloquine Hydrochloride

Pronunciation

Pronunciation: MEF-loe-kwin HYE-droe-KLOR-ide
Class: Antimalarial preparation

Trade Names

Mefloquine Hydrochloride
- Tablets, oral 250 mg

Apo-Mefloquine (Canada)

Pharmacology

Antimalarial agent that acts as a blood schizonticide. Mechanism of action is unknown.

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Pharmacokinetics

Absorption

T max is 6 to 24 h. Food enhances the rate and extent of absorption, increasing bioavailability approximately 40%.

Distribution

Vd is approximately 20 L/kg and the protein binding is 98%.

Metabolism

Metabolized in the liver by CYP3A4. Two metabolites have been identified.

Elimination

The total Cl is 30 mL/min and the half-life is between 2 and 4 wk (mean, approximately 3 wk).

Indications and Usage

Treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of Plasmodium falciparum or Plasmodium vivax . Prevention of malaria caused by P. falciparum or P. vivax .

Contraindications

Hypersensitivity to any component of the product or to related compounds (eg, quinine, quinidine); for prophylaxis in patients with active depression, generalized anxiety disorder, a recent history of depression, psychosis, or schizophrenia or other major psychiatric disorders, or with a history of convulsions.

Dosage and Administration

Treatment of Malaria
Adults

PO 1,250 mg as a single dose.

Children (6 mo and older)

PO 20 to 25 mg/kg as a single dose or split into 2 doses 6 to 8 h apart.

Prevention of Malaria
Adults

PO 250 mg once weekly starting 1 wk before exposure and continuing 4 wk after.

Children

PO 5 mg/kg once weekly starting with 1 wk before exposure and continuing 4 wk after.

Weight 20 to 30 kg

PO ½ tablet.

Weight 30 to 45 kg

PO ¾ tablet.

Weight more than 45 kg

PO 1 tablet.

General Advice

  • Administer with food and at least 240 mL of water.
  • The dose may be crushed and suspended in a small amount of water, milk, or other beverage.
  • Patients with acute P. vivax need subsequent treatment with 8-aminoquinoline derivative to prevent relapse.
  • If a full treatment course with mefloquine does not lead to improvement within 48 to 72 h, do not use mefloquine for re-treatment. Similarly, if prophylaxis with mefloquine has failed, do not use mefloquine for curative treatment.
  • In children, use of mefloquine has been associated with early vomiting. If a significant loss of drug product is observed or suspected because of vomiting, a second full dose should be administered to patients who vomit less than 30 min after receiving a dose. If vomiting occurs 30 to 60 min after a dose, an additional half-dose should be given. If vomiting recurs, monitor the patient closely and consider alternative treatment if improvement is not observed within a reasonable time frame.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin, valproic acid)

Reduced seizure control. Monitor anticonvulsant blood concentrations and adjust the dosage as necessary.

Bacterial vaccines, live (ie, oral live typhoid vaccines)

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

Beta-adrenergic blockers (ie, propranolol)

There has been 1 report of cardiopulmonary arrest with full recovery in a patient taking propranolol.

Chloroquine

The risk of convulsions may be increased with concomitant mefloquine. In addition, the risk of ECG abnormalities may be increased. If chloroquine is used in the initial treatment of severe malaria, delay mefloquine administration until at least 12 h after the last dose of chloroquine.

Drugs known to alter cardiac conduction (eg, antiarrhythmic, antidepressants, antihistamines, beta-adrenergic blockers, calcium channel blockers, H 2 blockers, paliperidone, tricyclic phenothiazines, ziprasidone)

Potential for QT interval prolongation. If coadministration is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when a new drug is added to a stable regimen of another QT-prolonging agent.

Halofantrine, ketoconazole

Concurrent use can cause potentially fatal QTc interval prolongation. Do not give halofantrine with or within 15 wk of the last dose of mefloquine.

Protease inhibitors (eg, ritonavir)

Protease inhibitor plasma concentrations may be reduced, decreasing the efficacy. Additional clinical monitoring is warranted.

Rabies vaccine

Antibody response to rabies vaccine may be decreased. Mean serum titers of rabies antibody may be lower than expected. International travelers should complete a 3-dose rabies vaccination series before starting mefloquine. If this is not possible, the rabies vaccine should be given IM and not intradermally.

Related compounds (eg, quinine, quinidine)

Increased risk of seizures and ECG abnormalities. If these agents are to be used in the initial treatment of severe malaria, delay mefloquine administration until at least 12 h after the last dose of quinine or quinidine.

Rifampin

Mefloquine plasma concentrations may be reduced, decreasing the pharmacologic effects. Coadminister with caution.

Warfarin

Anticoagulant effects of warfarin may be increased. Monitor anticoagulant activity and adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

AV block, bradycardia, chest pain, extrasystoles, flushing, hypertension, hypotension, irregular heart rate, syncope, tachycardia or palpitation (postmarketing).

CNS

Dizziness, fatigue, headache; aggression, agitation, anxiety, asthenia, confusion, convulsions, depression, encephalopathy, hallucinations, malaise, memory impairment, mood swings, panic attacks, psychotic or paranoid reactions, restlessness, sensory and motor neuropathies, sleep disorders, somnolence, suicidal ideation, suicide, vertigo (postmarketing).

Dermatologic

Skin rash; erythema, erythema multiforme, exanthema, hair loss, hyperhidrosis, pruritus, Stevens-Johnson syndrome, urticaria (postmarketing).

EENT

Tinnitus; vestibular disorders including hearing impairment, visual disturbances (postmarketing).

GI

Vomiting (3%); abdominal pain, diarrhea, loss of appetite, nausea; dyspepsia (postmarketing).

Hematologic

Leukocytosis, thrombocytopenia; agranulocytosis, aplastic anemia (postmarketing).

Hepatic

Drug-related hepatic disorders from asymptomatic transient transaminase elevations to hepatic failure (postmarketing).

Lab Tests

Decreased Hct, transient elevation of transaminases.

Musculoskeletal

Myalgia; arthralgia, muscle cramps, muscle weakness (postmarketing).

Respiratory

Dyspnea, pneumonitis of possible allergic etiology (postmarketing).

Miscellaneous

Chills; fever (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy in children younger than 6 mo have not been established.

Elderly

Weigh the benefits of therapy against the possibility of adverse cardiac effects in elderly patients.

Hypersensitivity

Reactions may occur, ranging from mild cutaneous events to anaphylaxis.

Hepatic Function

Elimination of mefloquine may be prolonged, leading to higher plasma levels and a higher risk of adverse reactions.

Special Risk Patients

Use with caution in patients with a history of depression or psychiatric disturbances.

CNS effects

May cause psychiatric symptoms ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior. Occasionally, these symptoms continue long after therapy with mefloquine has stopped. Rare cases of suicidal ideation and suicide have been reported.

CV effects

Risk of ECG alterations, sinus bradycardia, sinus arrhythmia, first-degree AV block, prolonged QTc interval, and abnormal T waves.

Epileptic patients

Increased risk of seizures.

Hematologic effects

Agranulocytosis and aplastic anemia have been reported.

Overdosage

Symptoms

ECG abnormalities, neuropsychiatric symptoms.

Patient Information

  • Instruct patients to read the Medication Guide before use and to carry the information wallet card with them.
  • Advise patients to take each prophylactic dose at the same time each day with food and at least 8 oz of water.
  • Instruct patients taking mefloquine for prophylaxis that the first dose should be taken 1 wk prior to arrival in a malaria-infected area and that subsequent doses should be taken on the same day of the week while in the malaria-infected area and for 4 wk after leaving the malaria-infected area.
  • Advise patients that protective clothing, insect repellants, and bednets are important components of malaria prophylaxis.
  • Instruct patients taking prophylactic doses to discontinue the drug and notify their health care provider immediately if any of the following develop: acute anxiety, depression, restlessness, confusion, paranoia, hallucinations, or change in behavior. Alternative therapy will be necessary if mefloquine is discontinued.
  • Advise patients to notify their health care provider if severe or persistent vomiting or diarrhea develops, vomiting within 1 h of taking a dose occurs often, other bothersome adverse reactions occur, or therapy is prematurely discontinued for any reason.
  • Advise patients that the drug may cause dizziness or other nervous system disorders, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patients that if a febrile illness develops during or after return from a malaria-endemic area, they should seek medical attention and inform their health care provider of possible malaria exposure.

Copyright © 2009 Wolters Kluwer Health.

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