DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ELIGLUSTAT

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIQT concern

Severity Score:3.0

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

WARNINGS AND PRECAUTIONS
ECG Changes and Potential for Cardiac Arrhythmias
CERDELGA is predicted to cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated eliglustat plasma concentrations and may increase the risk of cardiac arrhythmias.
Use of CERDELGA is contraindicated, to be avoided, or requires dosage adjustment in patients taking CYP2D6 or CYP3A inhibitors, depending CYP2D6 metabolizer status, type of inhibitor, or degree of hepatic impairment [see DOSAGE AND ADMINISTRATION (2.3), CONTRAINDICATIONS (4), DRUG INTERACTIONS (7.1)].
Use of CERDELGA in patients with pre-existing cardiac conditions has not been studied during clinical trials. Avoid use of CERDELGA in patients with:
pre-existing cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia)
long QT syndrome
in combination with Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications [see CLINICAL PHARMACOLOGY (12.2)].
DRUG INTERACTIONS
Effect of Other Drugs on CERDELGA
Coadministration of CERDELGA with:
CYP2D6 or CYP3A inhibitors may increase eliglustat concentrations which may increase the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac interval [see WARNINGS AND PRECAUTIONS (5.1), CLINICAL PHARMACOLOGY (12.3)].
strong CYP3A inducers decreases eliglustat concentrations which may reduce CERDELGA efficacy [see CLINICAL PHARMACOLOGY (12.3)].
CONTRAINDICATIONS
CERDELGA is contraindicated in the following patients based on CYP2D6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
Concentration-related increases were observed for the placebo-corrected change from baseline in the PR, QRS, and QTc intervals. At the mean peak concentration of 237 ng/mL at a dose of 800 mg eliglustat tartrate (8 times the recommended dose), CERDELGA did not prolong the QT/QTc interval to any clinically relevant extent. However, pharmacokinetic/pharmacodynamic modeling predicts mean (upper bound of the 95% one-sided confidence interval) increases in the PR, QRS, and QTcF intervals of 22 (26), 7 (10), and 13 (19) msec, respectively, at eliglustat plasma concentration of 500 ng/mL [see WARNINGS AND PRECAUTIONS (5.1)].
PATIENT COUNSELING INFORMATION
ECG Changes and Potential for Cardiac Arrhythmias
Advise patients to inform their healthcare provider of the following: history of congestive heart failure; recent acute myocardial infarction; bradycardia; heart block; ventricular arrhythmia; and long QT syndrome [see WARNINGS AND PRECAUTIONS (5.1)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24091

Other ADRs

1142

38380445

Odds Ratio = 1.396

Drug Property Information

ATC Code(s):

A16AX10 - eliglustat

A16AX - Various alimentary tract and metabolism products
A16A - OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
A16 - OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
A - ALIMENTARY TRACT AND METABOLISM

Active Ingredient:eliglustat

Active Ingredient UNII:DR40J4WA67

Drugbank ID:DB09039

PubChem Compound:23652731

CTD ID:C522917

PharmGKB:PA166123486

CAS Number:491833-29-5

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

168.0 mg/day A16AX10

Chemical Structure:

SMILE Code:
CCCCCCCC(=O)N[C@H](CN1CCCC1)[C@H](O)C1=CC=C2OCCOC2=C1

Reference

N/A