DIQTA 1.0: Drug-Induced QT Prolongation Atlas

DASATINIB

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

WARNINGS AND PRECAUTIONS
QT Prolongation
In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarization (QT interval). Of the 2440 patients with CML treated with SPRYCEL in clinical studies, 15 patients (<1%) had QTc prolongation reported as an adverse reaction. Twenty-two patients (1%) experienced a QTcF >500 ms. In 865 patients with leukemia treated with SPRYCEL in five Phase 2 single-arm studies, the maximum mean changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 ms to 13.4 ms.
Administer SPRYCEL with caution to patients who have or may develop prolongation of QTc. These include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy. Correct hypokalemia or hypomagnesemia prior to SPRYCEL administration.
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Myelosuppression [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
Bleeding related events [see Warnings and Precautions (5.2)].
Fluid retention [see Warnings and Precautions (5.3)].
QT prolongation [see Warnings and Precautions (5.4)].
Congestive heart failure, left ventricular dysfunction, and myocardial infarction [see Warnings and Precautions (5.5)].
Pulmonary Arterial Hypertension [see Warnings and Precautions (5.6)].
CLINICAL STUDIES
Chronic Phase CML
Dose-Optimization Study: A randomized, open-label study was conducted in patients with chronic phase CML to evaluate the efficacy and safety of SPRYCEL administered once daily compared with SPRYCEL administered twice daily. Patients with significant cardiac diseases, including myocardial infarction within 6 months, congestive heart failure within 3 months, significant arrhythmias, or QTc prolongation were excluded from the study. The primary efficacy endpoint was MCyR in patients with imatinib-resistant CML. A total of 670 patients, of whom 497 had imatinib-resistant disease, were randomized to the SPRYCEL 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily group. Median duration of treatment was 22 months.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24039

Other ADRs

47469

38334118

Odds Ratio = 1.781

Drug Property Information

ATC Code(s):

L01EA02 - dasatinib

L01EA -
L01E -
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:dasatinib

Active Ingredient UNII:RBZ1571X5H

Drugbank ID:DB01254

PubChem Compound:3062316

CTD ID: D000069439

PharmGKB:PA162372878

CAS Number:302962-49-8

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1

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