DIQTA 1.0: Drug-Induced QT Prolongation Atlas

QUETIAPINE FUMARATE

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 Prolongation
In clinical trials quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10.1)], in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval.
The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone).
Quetiapine should also be avoided in circumstances that may increase the risk of occurrence of torsade de pointes and/or sudden death including (1) a history of cardiac arrhythmias such as bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval.
Caution should also be exercised when quetiapine is prescribed in patients with increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure and heart hypertrophy).
OVERDOSAGE
Human Experience
In clinical trials, survival has been reported in acute overdoses of up to 30 grams of quetiapine. Most patients who overdosed experienced no adverse reactions or recovered fully from the reported events. Death has been reported in a clinical trial following an overdose of 13.6 grams of quetiapine alone. In general, reported signs and symptoms were those resulting from an exaggeration of the drug’s known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and anticholinergic toxicity including coma and delirium. Patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of overdose [see WARNINGS AND PRECAUTIONS (5.12)]. One case, involving an estimated overdose of 9600 mg, was associated with hypokalemia and first degree heart block. In post-marketing experience, there were cases reported of QT prolongation with overdose.
ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the labeling:
QT Prolongation [see WARNINGS AND PRECAUTIONS( 5.12)]
CLINICAL PHARMACOLOGY
Effect on QT Interval
In clinical trials quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10.1)], in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

934

23158

Other ADRs

235660

38145927

Odds Ratio = 6.529

Drug Property Information

ATC Code(s):

N05AH04 - quetiapine fumarate

N05AH - "Diazepines, oxazepines and thiazepines"
N05A - ANTIPSYCHOTICS
N05 - PSYCHOLEPTICS
N - NERVOUS SYSTEM

Active Ingredient:QUETIAPINE FUMARATE

Active Ingredient UNII:2S3PL1B6UJ

Drugbank ID:DB01224

PubChem Compound:5002

CTD ID:D000069348

PharmGKB:PA451201

CAS Number:111974-69-7

Dosage Form(s):tablet, extended release

Route(s) Of Administrator:oral

Daily Dose:

400.0 mg/day N05AH04

Chemical Structure:

SMILE Code:
OCCOCCN1CCN(CC1)C1=NC2=CC=CC=C2SC2=CC=CC=C12

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