DIQTA 1.0: Drug-Induced QT Prolongation Atlas

GEMIFLOXACIN MESYLATE

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
QT Effects: Fluoroquinolones may prolong the QT interval in some patients. FACTIVE should be avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
Pharmacokinetic studies between gemifloxacin and drugs that prolong the QTc interval such as erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. FACTIVE should be used with caution when given concurrently with these drugs, as well as in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia. No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with FACTIVE treatment in over 8119 patients, including 707 patients concurrently receiving drugs known to prolong the QTc interval and 7 patients with hypokalemia.
The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. QTc prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin.
PRECAUTIONS
Inform patients of the following serious adverse reactions that have been associated with FACTIVE or other fluoroquinolone use:
Prolongation of the QT interval: inform patients of the following:that FACTIVE may cause changes in the electrocardiogram (QTc interval prolongation);
that FACTIVE may cause changes in the electrocardiogram (QTc interval prolongation);
that FACTIVE should be avoided in patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents;
that FACTIVE should be used with caution in patients receiving drugs that affect the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants;
to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia;
to contact their physician if they experience palpitations or fainting spells while taking FACTIVE;
[Geriatric Use:]
Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, FACTIVE should be avoided in patients taking drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).
ADVERSE REACTIONS
Post-Marketing Adverse Reactions
The following are additional adverse reactions reported during the post-marketing use of FACTIVE. Since these reactions are reported voluntarily from a population of uncertain size, it is impossible to reliably estimate their frequency or establish a causal relationship to FACTIVE exposure:
peripheral neuropathy that may be irreversible;
anaphylactic reaction, erythema multiforme, skin exfoliation, facial swelling;
exacerbation of myasthenia gravis;
hemorrhage, increased international normalized ratio (INR), retinal hemorrhage;
peripheral edema;
renal failure;
prolonged QT, supraventricular tachycardia, syncope, transient ischemic attack;
photosensitivity/phototoxicity reaction (See PRECAUTIONS.);
antibiotic-associated colitis;
tendon rupture.
MEDICATION GUIDE
What are the possible side effects of FACTIVE?
Serious heart rhythm changes (QTc prolongation and torsades de pointes)
Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you faint. FACTIVE may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:
who are elderly
with a family history of prolonged QT interval
with low blood potassium (hypokalemia)
who take certain medicines to control heart rhythm (antiarrhythmics).
ANIMAL PHARMACOLOGY
Quinolones have been associated with prolongation of the electrocardiographic QT interval in dogs. Gemifloxacin produced no effect on the QT interval in dogs dosed orally to provide about 4 times human therapeutic plasma concentrations at Cmax, and transient prolongation after intravenous administration at more than 4 times human plasma levels at Cmax. Gemifloxacin exhibited weak activity in the cardiac IKr (hERG) channel inhibition assay, having an IC50 of approximately 270 渭M.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24091

Other ADRs

2493

38379094

Odds Ratio = 0.64

Drug Property Information

ATC Code(s):

J01MA15 - gemifloxacin mesylate

J01MA - Fluoroquinolones
J01M - QUINOLONE ANTIBACTERIALS
J01 - ANTIBACTERIALS FOR SYSTEMIC USE
J - ANTIINFECTIVES FOR SYSTEMIC USE

Active Ingredient:GEMIFLOXACIN MESYLATE

Active Ingredient UNII:X4S9F8RL01

Drugbank ID:DB01155

PubChem Compound:9571107

CTD ID: D000077735

PharmGKB:PA10088

CAS Number:175463-14-6

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

320.0 mg/day J01MA15

Chemical Structure:

SMILE Code:
CO\N=C1/CN(CC1CN)C1=NC2=C(C=C1F)C(=O)C(=CN2C1CC1)C(O)=O

Reference

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