DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ENTRECTINIB

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 Interval Prolongation
Among the 355 patients who received ROZLYTREK across the clinical trials, 3.1% of patients with at least one post-baseline ECG assessment experienced QTcF interval prolongation of > 60 ms after starting ROZLYTREK and 0.6% had a QTcF interval > 500 ms [see ADVERSE REACTIONS (6.1), CLINICAL PHARMACOLOGY (12.2)].
Monitor patients who already have or who are at significant risk of developing QTc interval prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Assess QT interval and electrolytes at baseline and periodically during treatment, adjusting frequency based upon risk factors such as congestive heart failure, electrolyte abnormalities, or concomitant medications known to prolong the QTc interval. Based on the severity of QTc interval prolongation, withhold ROZLYTREK and then resume at same or reduced dose, or permanently discontinue [see DOSAGE AND ADMINISTRATION (2.4)].
DRUG INTERACTIONS
Drugs That Prolong QT Interval
QTc interval prolongation can occur with ROZLYTREK. Avoid coadministration of ROZLYTREK with other products with a known potential to prolong QT/QTc interval [see WARNINGS AND PRECAUTIONS (5.6), CLINICAL PHARMACOLOGY (12.2)].
DOSAGE AND ADMINISTRATION
ADVERSE REACTIONS
Clinically relevant adverse reactions occurring in ≤ 10% of patients include dysphagia (10%), fall (8%), pleural effusion (8%), fractures (6%), hypoxia (4.2%), pulmonary embolism (3.9%), syncope (3.9%), congestive heart failure (3.4%), and QT prolongation (3.1%).
CLINICAL PHARMACOLOGY
Pharmacodynamics
Entrectinib exposure-response relationships and the time course of pharmacodynamic responses are unknown.
Cardiac Electrophysiology
Across clinical trials, 3.1% of 355 patients, who received ROZLYTREK at doses ranging from 100 mg to 2600 mg daily under fasting or fed conditions (75% received 600 mg orally once daily) and had at least one post-baseline ECG assessment, experienced QTcF interval prolongation of > 60 ms after starting ROZLYTREK and 0.6% had a QTc interval > 500 ms [see WARNINGS AND PRECAUTIONS (5.6)].
PATIENT COUNSELING INFORMATION
QT Interval Prolongation
Inform patients of the risks of QT interval prolongation and to advise patients to contact their healthcare provider immediately for any symptoms of QT interval prolongation [see WARNINGS AND PRECAUTIONS (5.6)].
PATIENT PACKAGE INSERT
ROZLYTREK may cause serious side effects, including:
Changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. Your healthcare provider will do tests before and during your treatment with ROZLYTREK to check the electrical activity of your heart and your body salts (electrolytes). Tell your healthcare provider right away if you feel faint, lightheaded, dizzy, or feel your heart beating irregularly or fast during your treatment with ROZLYTREK. These may be symptoms related to QT prolongation.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24091

Other ADRs

420

38381167

Odds Ratio = 3.794

Drug Property Information

ATC Code(s):

L01EX14 - entrectinib

L01EX -
L01E -
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:ENTRECTINIB

Active Ingredient UNII:L5ORF0AN1I

Drugbank ID:DB11986

PubChem Compound:25141092

CTD ID:C000607349

PharmGKB:

CAS Number:1108743-60-7

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
CN1CCN(CC1)C1=CC=C(C(=O)NC2=NNC3=CC=C(CC4=CC(F)=CC(F)=C4)C=C23)C(NC2CCOCC2)=C1

Reference

1: {'i': 'NTRK', '#text': 'FDA Approval Summary: Entrectinib for the Treatment of gene Fusion Solid Tumors.'}

[Marcus Leigh,Donoghue Martha,Aungst Stephanie,Myers Claire E,Helms Whitney S,Shen Guoxiang,Zhao Hong,Stephens Olen,Keegan Patricia,Pazdur Richard]
Clin Cancer Res,2021 Feb 15;27(4):928-932. PMID: 32967940

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