GILENYA™ (fingolimod Hcl)

(description)

Clinical pharmacology

Indications and usage

Contraindications

Precautions

Adverse reactions

Dosage and administration

How supplied

Reference

(description)

Initial U.S. Approval: 2010
DESCRIPTION
Fingolimod is a sphingosine 1-phosphate receptor modulator.

Chemically, fingolimod is 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol hydrochloride.
Fingolimod hydrochloride is a white to practically white powder that is freely soluble in water and alcohol and soluble in propylene glycol. It has a molecular weight of 343.93.

GILENYA is provided as 0.5 mg hard gelatin capsules for oral use. Each capsule contains 0.56 mg of fingolimod hydrochloride, equivalent to 0.5 mg of fingolimod.

Each GILENYA 0.5 mg capsule contains the following inactive ingredients: gelatin, magnesium stearate, mannitol, titanium dioxide, yellow iron oxide.

Clinical pharmacology

CLINICAL PHARMACOLOGY
Mechanism of Action
Fingolimod is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

Indications and usage

GILENYA is a sphingosine 1-phosphate receptor modulator indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.

Contraindications

None.

Precautions

WARNINGS AND PRECAUTIONS

Decrease in heart rate and/or atrioventricular conduction after first dose of GILENYA: Observe all patients for signs and symptoms of bradycardia for 6 hours after first dose. Obtain baseline ECG before first dose if not recently available in those at higher risk of bradyarrhythmia. Patients receiving Class Ia or Class III antiarrhythmic drugs, beta blockers, calcium channel blockers, those with a low heart rate, history of syncope, sick sinus syndrome, 2nd degree or higher conduction block, ischemic heart disease, or congestive heart failure are at increased risk of developing bradycardia or heart blocks.
Infections: GILENYA may increase the risk of infections. A recent CBC should be available before initiating treatment with GILENYA. Monitor for signs and symptoms of infection during treatment and for two months after discontinuation. Do not start GILENYA treatment in patients with active acute or chronic infections.
Macular edema: Can occur with or without visual symptoms. An ophthalmologic evaluation should be performed before starting GILENYA and at 3-4 months after treatment initiation. Monitor visual acuity at baseline and during routine evaluations of patients. Patients with diabetes mellitus or a history of uveitis are at increased risk and should have regular ophthalmologic evaluations.
Decrease in pulmonary function tests with GILENYA: Obtain spirometry and diffusion lung capacity for carbon monoxide (DLCO) when clinically indicated.
Hepatic effects: GILENYA may increase liver transaminases. Recent liver enzyme results should be available before initiating treatment with GILENYA. Assess liver enzymes if symptoms suggestive of hepatic injury develop. Discontinue GILENYA if significant liver injury is confirmed.
Fetal risk: Women of childbearing potential should use effective contraception during and for two months after stopping GILENYA treatment.

DRUG INTERACTIONS
Class Ia or Class III antiarrhythmic drugs: Because of a risk of serious rhythm disturbances, carefully monitor patients on Class Ia or Class III antiarrhythmic drugs during initiation of therapy.

Beta blockers: Because of a risk of additive effect on heart rate, carefully monitor patients on beta blockers during initiation of therapy.

Ketoconazole: Monitor patients closely, as GILENYA exposure is increased by70% during concomitant use with systemic ketoconazole, and risk of adverse reactions is greater.

Vaccines: Avoid live attenuated vaccines during, and for 2 months after stopping GILENYA treatment, due to risk of infection.

USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. Pregnancy registry available.

Pediatric patients: Safety and effectiveness have not been established.

Hepatic impairment: Monitor patients with severe hepatic impairment closely, as GILENYA exposure is doubled, and risk of adverse reactions is greater.

Adverse reactions

Most common adverse reactions (incidence ≥10% and > placebo): Headache, influenza, diarrhea, back pain, liver transaminase elevations and cough.

Dosage and administration

The recommended dose of GILENYA is 0.5 mg orally once daily. Patients should be observed for 6 hours after the first dose to monitor for signs and symptoms of bradycardia [see Warnings and Precautions]. Fingolimod doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefit.

GILENYA can be taken with or without food.

How supplied

GILENYA is available as 0.5 mg hard capsules with a white opaque body and bright yellow cap imprinted with “FTY 0.5 mg” on the cap and two radial bands imprinted on the capsule body with yellow ink.

Reference

Package Insert data:
GILENYA is a trademark of Novartis AG.
Manufactured by:
Novartis Pharma Stein AG
Stein, Switzerland

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936
© Novartis
T2011-104/T2010-82
July 2011/September 2010

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here.