DIQTA 1.0: Drug-Induced QT Prolongation Atlas

FINGOLIMOD HCL

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
Bradyarrhythmia and Atrioventricular Blocks
Since initiation of GILENYA treatment, results in decreased heart rate and may prolong the QT interval, patients with a prolonged QTc interval (> 450 msec adult and pediatric males, > 470 msec adult females, or > 460 msec pediatric females) before dosing or during 6-hour observation, or at additional risk for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome), or on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) should be monitored overnight with continuous ECG in a medical facility
DRUG INTERACTIONS
QT Prolonging Drugs
GILENYA has not been studied in patients treated with drugs that prolong the QT interval. Drugs that prolong the QT interval have been associated with cases of torsades de pointes in patients with bradycardia. Since initiation of GILENYA treatment results in decreased heart rate and may prolong the QT interval, patients on QT prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) should be monitored overnight with continuous ECG in a medical facility [see Dosage and Administration (2.4), Warnings and Precautions (5.1)].
CONTRAINDICATIONS
GILENYA is contraindicated in patients who have:
a baseline QTc interval ≥ 500 msec
DOSAGE AND ADMINISTRATION
First-Dose Monitoring
Overnight Monitoring
Continuous overnight ECG monitoring in a medical facility should be instituted:
in patients with a prolonged QTc interval before dosing or during 6-hour observation, or at additional risk for QT prolongation, or on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes [see Warnings and Precautions (5.1), Drug Interactions (7.1)];
CLINICAL PHARMACOLOGY
Pharmacodynamics
Potential to Prolong the QT Interval
In a thorough QT interval study of doses of 1.25 or 2.5 mg fingolimod at steady-state, when a negative chronotropic effect of fingolimod was still present, fingolimod treatment resulted in a prolongation of QTc, with the upper boundary of the 90% confidence interval (CI) of 14.0 msec. There is no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment. In MS studies, there was no clinically relevant prolongation of the QT interval, but patients at risk for QT prolongation were not included in clinical studies.
MEDICATION GUIDE
Who should not take GILENYA?
Do not take GILENYA if you:
have certain types of irregular or abnormal heartbeat (arrhythmia), including patients in whom a heart finding called prolonged QT is seen on ECG before starting GILENYA.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

331

23761

Other ADRs

241411

38140176

Odds Ratio = 2.201

Drug Property Information

ATC Code(s):

L04AA27 - fingolimod hcl

L04AA - Selective immunosuppressants
L04A - IMMUNOSUPPRESSANTS
L04 - IMMUNOSUPPRESSANTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:FINGOLIMOD HYDROCHLORIDE

Active Ingredient UNII:G926EC510T

Drugbank ID:DB08868

PubChem Compound:107970

CTD ID:D000068876

PharmGKB:

CAS Number:162359-55-9

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

0.5 mg/day L04AA27

Chemical Structure:

SMILE Code:
CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1

Reference

N/A