DIQTA 1.0: Drug-Induced QT Prolongation Atlas

MEFLOQUINE HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Most-DIQT concern

Severity Score:4.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

WARNINGS
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.
PRECAUTIONS
Cardiac Effects
Parenteral studies in animals show that mefloquine, a myocardial depressant, possesses 20% of the anti-fibrillatory action of quinidine and produces 50% of the increase in the PR interval reported with quinine. The effect of mefloquine on the compromised cardiovascular system has not been evaluated. However, transitory and clinically silent ECG alterations have been reported during the use of mefloquine; alterations included sinus bradycardia, sinus arrhythmia, first degree AV-block, prolongation of the QTc interval and abnormal T waves (see also cardiovascular effects under PRECAUTIONS, DRUG INTERACTIONS and ADVERSE REACTIONS). The benefits of mefloquine therapy should be weighed against the possibility of adverse effects in patients with cardiac disease.
[Drug Interactions]
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 Cmax 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 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.
MEDICATION GUIDE
Mefloquine can cause serious side effects, including:
[Heart Problems]
Do not take halofantrine (used to treat malaria) or ketoconazole (used for fungal infections) with
mefloquine or within 15 weeks of your last dose of mefloquine. You may get serious heart
problems (problems with the electrical system of your heart called QT prolongation) that can lead
to death. Do not take quinine (Qualaquin) or quinidine (used to treat malaria or irregular heart
beat) with mefloquine. You may get serious heart problems.
Mefloquine can cause serious side effects,including:
[Heart problems]
Do not take halofantrine (used to treat malaria) or ketoconazole (used for fungal infections) with mefloquine or within 15 weeks of your last dose of mefloquine. You may get serious heart problems that can lead to death. Do not take quinine (Qualaquin) or quinidine (used to treat malaria or irregular heart beat) with mefloquine. You may get serious heart problems. Mefloquine may cause serious problems with the electrical system of your heart, called QT prolongation.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24085

Other ADRs

7387

38374200

Odds Ratio = 1.51

Drug Property Information

ATC Code(s):

P01BC02 - mefloquine hydrochloride

P01BC0 -
P01BC - Methanolquinolines
P01B - ANTIMALARIALS
P01 - ANTIPROTOZOALS
P - "ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS"

Active Ingredient:MEFLOQUINE HYDROCHLORIDE

Active Ingredient UNII:5Y9L3636O3

Drugbank ID:DB00358

PubChem Compound:4046

CTD ID:D015767

PharmGKB:PA450348

CAS Number:53230-10-7

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

1000.0 mg/day P01BC02

Chemical Structure:

SMILE Code:
OC(C1CCCCN1)C1=CC(=NC2=C1C=CC=C2C(F)(F)F)C(F)(F)F

Reference

N/A