DIQTA 1.0: Drug-Induced QT Prolongation Atlas

SORAFENIB

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
NEXAVAR can prolong the QT/QTc interval. QT/QTc interval prolongation increases the risk for ventricular arrhythmias.
Avoid NEXAVAR in patients with congenital long QT syndrome. Monitor electrolytes and electrocardiograms in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Correct electrolyte abnormalities (magnesium, potassium, calcium). Interrupt NEXAVAR if QTc interval is greater than 500 milliseconds or for an increase from baseline of 60 milliseconds or greater [see Clinical Pharmacology (12.2)].
DRUG INTERACTIONS
Drugs That Prolong the QT Interval
NEXAVAR is associated with QTc interval prolongation. Avoid coadministration of NEXAVAR with medicinal products with a known potential to prolong QT/QTc interval [see Warnings and Precautions (5.9), Clinical Pharmacology (12.2)].
DOSAGE AND ADMINISTRATION
ADVERSE REACTIONS
The following clinically significant adverse reactions are discussed elsewhere in the labeling:•
Cardiovascular events [see Warnings and Precautions (5.1)]
Hemorrhage [see Warnings and Precautions (5.2)]
Hypertension [see Warnings and Precautions (5.3)]
Dermatologic toxicities [see Warnings and Precautions (5.4)]
Gastrointestinal perforation [see Warnings and Precautions (5.5)]
QT interval prolongation [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.2)]
Drug-induced liver injury [see Warnings and Precautions (5.10)]
Impairment of TSH suppression in DTC [see Warnings and Precautions (5.12)]
[Additional Data from Multiple Clinical Trials]
Cardiovascular: Common: congestive heart failure*†, myocardial ischemia and/or infarction Uncommon: hypertensive crisis* Rare: QT prolongation*
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of NEXAVAR 400 mg twice daily on the QTc interval was evaluated in a multi-center, open-label, non-randomized trial in 53 patients with advanced cancer. No large changes in the mean QTc intervals (that is, >20 ms) from baseline were detected in the trial. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2 [see Warnings and Precautions (5.9), Drug Interactions (7.3)].
PATIENT COUNSELING INFORMATION
QT Interval Prolongation
Inform patients with a history of prolonged QT interval that NEXAVAR can worsen the condition [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.2)].
NEXAVAR 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 may do tests during your treatment with NEXAVAR to check the levels of potassium, magnesium, and calcium in your blood, and check the electrical activity of your heart with an electrocardiogram (ECG). Tell your healthcare provider right away if you feel faint, lightheaded, dizzy or feel your heart beating irregularly or fast during your treatment with NEXAVAR.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24080

Other ADRs

13755

38367832

Odds Ratio = 1.391

Drug Property Information

ATC Code(s):

L01EX02 - sorafenib

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

Active Ingredient:SORAFENIB

Active Ingredient UNII:9ZOQ3TZI87

Drugbank ID:DB00398

PubChem Compound:216239

CTD ID:D000077157

PharmGKB:PA7000

CAS Number:284461-73-0

Dosage Form(s):tablet, film coated

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

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