DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ONDANSETRON 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 AND PRECAUTIONS
QT Prolongation
Electrocardiogram (ECG) changes including QT interval prolongation have been seen in patients receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation [see CLINICAL PHARMACOLOGY (12.2)] .
ADVERSE REACTIONS
Postmarketing Experience
Cardiovascular
Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
QTc interval prolongation was studied in a double-blind, single-intravenous dose, placebo- and positive- controlled, crossover trial in 58 healthy subjects. The maximum mean (95% upper confidence bound) difference in QTcF from placebo after baseline correction was 19.5 (21.8) milliseconds and 5.6 (7.4) milliseconds after 15- minute intravenous infusions of 32 mg and 8 mg of ondansetron injection, respectively. A significant exposure- response relationship was identified between ondansetron concentration and ΔΔQTcF. Using the established exposure-response relationship, 24 mg infused intravenously over 15 minutes had a mean predicted (95% upper prediction interval) ΔΔQTcF of 14.0 (16.3) milliseconds. In contrast, 16 mg infused intravenously over 15 minutes using the same model had a mean predicted (95% upper prediction interval) ΔΔQTcF of 9.1 (11.2) milliseconds. In this study, the 8 mg dose infused over 15 minutes did not prolong the QT interval to any clinically relevant extent.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

383

23709

Other ADRs

49763

38331824

Odds Ratio = 12.444

Drug Property Information

ATC Code(s):

A04AA01 - ondansetron hydrochloride

A04AA - Serotonin (5HT3) antagonists
A04A - ANTIEMETICS AND ANTINAUSEANTS
A04 - ANTIEMETICS AND ANTINAUSEANTS
A - ALIMENTARY TRACT AND METABOLISM

Active Ingredient:ONDANSETRON HYDROCHLORIDE

Active Ingredient UNII:NMH84OZK2B

Drugbank ID:DB00904

PubChem Compound:4595

CTD ID:D017294

PharmGKB:PA450705

CAS Number:99614-02-5

Dosage Form(s):tablet, film coated

Route(s) Of Administrator:oral

Daily Dose:

16.0 mg/day A04AA01

Chemical Structure:

SMILE Code:
CN1C2=C(C3=CC=CC=C13)C(=O)C(CN1C=CN=C1C)CC2

Reference

N/A