DIQTA 1.0: Drug-Induced QT Prolongation Atlas

CRIZOTINIB

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
QT Interval Prolongation
QTc prolongation can occur in patients treated with XALKORI. Across clinical trials, 2.1% of 1616 patients had QTcF (corrected QT for heart rate by the Fridericia method) greater than or equal to 500 ms and 5% of 1582 patients had an increase from baseline QTcF greater than or equal to 60 ms by automated machine-read evaluation of ECGs.
Avoid use of XALKORI in patients with congenital long QT syndrome. Monitor ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QT interval. Withhold, reduce dose, or permanently discontinue XALKORI for QT/QTc interval prolongation as recommended [see DOSAGE AND ADMINISTRATION (2.3), CLINICAL PHARMACOLOGY (12.2)].
DRUG INTERACTIONS
Drugs That Prolong the QT Interval
XALKORI can prolong the QT/QTc interval. Avoid concomitant use of XALKORI with drugs that prolong the QT interval [see WARNINGS AND PRECAUTIONS (5.3), CLINICAL PHARMACOLOGY (12.2)].
DOSAGE AND ADMINISTRATION
ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
Hepatotoxicity [see WARNINGS AND PRECAUTIONS (5.1)]
Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS (5.2)]
QT Interval Prolongation [see WARNINGS AND PRECAUTIONS (5.3)]
Bradycardia [see WARNINGS AND PRECAUTIONS (5.4)]
Severe Visual Loss [see WARNINGS AND PRECAUTIONS (5.5)]
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
In an ECG substudy conducted in 52 patients with ALK-positive NSCLC, the maximum mean QTcF (corrected QT by the Fridericia method) change from baseline was 12.3 ms (2-sided 90% upper CI: 19.5 ms) following administration of XALKORI 250 mg orally twice daily. An exposure-QT analysis suggested a crizotinib plasma concentration-dependent increase in QTcF [see WARNINGS AND PRECAUTIONS (5.3)].
PATIENT PACKAGE INSERT
What should I tell my healthcare provider before taking XALKORI?
Before you take XALKORI, tell your healthcare provider if you:
have heart problems, including a condition called long QT syndrome
have liver or kidney problems
have vision or eye problems
have any other medical conditions

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24033

Other ADRs

22819

38358768

Odds Ratio = 4.127

Drug Property Information

ATC Code(s):

L01ED01 - crizotinib

L01ED -
L01E -
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:CRIZOTINIB

Active Ingredient UNII:53AH36668S

Drugbank ID:DB08865

PubChem Compound:11626560

CTD ID:D000077547

PharmGKB:PA165946122

CAS Number:877399-52-5

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl

Reference

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