DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ANAGRELIDE 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
Cardiovascular Toxicity
Torsades de pointes and ventricular tachycardia have been reported with anagrelide. Obtain a pre-treatment cardiovascular examination including an ECG in all patients. During treatment with anagrelide monitor patients for cardiovascular effects and evaluate as necessary.
Anagrelide increases the QTc interval of the electrocardiogram and increases the heart rate in healthy volunteers [see Clinical Pharmacology (12.2)].
Do not use anagrelide in patients with known risk factors for QT interval prolongation, such as congenital long QT syndrome, a known history of acquired QTc prolongation, medicinal products that can prolong QTc interval and hypokalemia [see Drug Interactions (7.1)].
Hepatic impairment increases anagrelide exposure and could increase the risk of QTc prolongation. Monitor patients with hepatic impairment for QTc prolongation and other cardiovascular adverse reactions. The potential risks and benefits of anagrelide therapy in a patient with mild and moderate hepatic impairment should be assessed before treatment is commenced. Reduce anagrelide dose in patients with moderate hepatic impairment. Avoid use of anagrelide in patients with severe hepatic impairment.
DRUG INTERACTIONS
Drugs that Prolong QT
Avoid use of anagrelide in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide) [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2)].
CLINICAL PHARMACOLOGY
Cardiac Electrophysiology
The effect of anagrelide dose (0.5 mg and 2.5 mg single doses) on the heart rate and QTc interval prolongation potential was evaluated in a double-blind, randomized, placebo- and active-controlled, cross-over study in 60 healthy adult men and women.
A dose-related increase in heart rate was observed, with the maximum increase occurring around the time of maximal drug concentration (0.5 to 4 hours). The maximum change in mean heart rate occurred at 2 hours after administration and was +7.8 beats per minute (bpm) for 0.5 mg and +29.1 bpm for 2.5 mg.
Dose-related increase in mean QTc was observed. The maximum mean (95% upper confidence bound) change in QTcI (individual subject correction) from placebo after baseline-correction was 7 (9.8) ms and 13 (15.7) ms following anagrelide doses of 0.5 mg and 2.5 mg, respectively.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24086

Other ADRs

3740

38377847

Odds Ratio = 2.557

Drug Property Information

ATC Code(s):

L01XX35 - anagrelide hydrochloride

L01XX - Other antineoplastic agents
L01X - OTHER ANTINEOPLASTIC AGENTS
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:ANAGRELIDE HYDROCHLORIDE

Active Ingredient UNII:VNS4435G39

Drugbank ID:DB00261

PubChem Compound:2182

CTD ID:C021139

PharmGKB:PA164742986

CAS Number:68475-42-3

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
ClC1=CC=C2N=C3NC(=O)CN3CC2=C1Cl

Reference

N/A