DIQTA 1.0: Drug-Induced QT Prolongation Atlas

PALONOSETRON HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Ambiguous

Severity Score:1.0

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

ADVERSE REACTIONS
Less common adverse reactions, reported in 1% or less of patients, in Studies 1, 2 and 3 were:
Cardiovascular: non-sustained tachycardia, bradycardia, hypotension, hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation.
[Clinical Trials Experience]
The most common adverse reactions reported in at least 2% of adults receiving palonosetron 0.075 mg intravenously immediately before induction of anesthesia in 3 randomized placebo-controlled trials [see CLINICAL STUDIES (14.3)] are shown in Table 3. Rates of adverse reactions between palonosetron and placebo groups were similar. Some events are known to be associated with, or may be exacerbated by concomitant perioperative and intraoperative medications administered in this surgical population. A thorough QT/QTc study demonstrated palonosetron does not prolong the QT interval to any clinically relevant extent [see CLINICAL PHARMACOLOGY (12.2)].
Less common adverse reactions, reported in 1% of less of patients, in these PONV clinical trials were:
Cardiovascular: QTc prolongation, sinus bradycardia, tachycardia, blood pressure decreased, hypotension, hypertension, arrhythmia, ventricular extrasystoles, generalized edema, ECG T wave amplitude decreased, platelet count decreased. The frequency of these adverse effects did not appear to be different from placebo.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of intravenous palonosetron on blood pressure, heart rate, and ECG parameters including QTc were comparable to intravenous ondansetron and dolasetron in CINV clinical trials. In PONV clinical trials the effect of palonosetron on the QTc interval was no different from placebo. In non-clinical studies palonosetron possesses the ability to block ion channels involved in ventricular de- and re-polarization and to prolong action potential duration.
At a dose of 9 times the maximum recommended adult dose, palonosetron does not prolong the QT interval to any clinically relevant extent.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24085

Other ADRs

1791

38379796

Odds Ratio = 6.229

Drug Property Information

ATC Code(s):

A04AA05 - palonosetron hydrochloride

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

A04AA55 - palonosetron hydrochloride

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

Active Ingredient:PALONOSETRON HYDROCHLORIDE

Active Ingredient UNII:23310D4I19

Drugbank ID:DB00377

PubChem Compound:6337614

CTD ID:D000077924

PharmGKB:PA10352

CAS Number:135729-56-5

Dosage Form(s):injection, solution

Route(s) Of Administrator:intravenous

Daily Dose:

0.5 mg/day A04AA05

Chemical Structure:

SMILE Code:
[H][C@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2

Reference

N/A