Fingolimod

What is Fingolimod?

• Fingolimod (GILENYA) is a sphingosine 1-phosphate receptor modulator used to treat relapsing multiple sclerosis.

Fingolimod structure

Fingolimod2DACS

Fingolimod-3D-balls-by-AHRLS-2011

What are the uses of this medicine?

• Fingolimod (GILENYA) is used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome,relapsing-remitting disease, and active secondary progressive disease, in adults and children 10 years of age and older.

How does this medicine work?

• Fingolimod (fin gol' i mod) is an immunomodulatory agent that is believed to act by inhibition of sphingosine-1-phosphate receptors. Fingolimod is a derivative of myriocin, a metabolite of the fungus Isaria sinclairii and is a structural analogue of sphingosine.
• Once phosphorylated intracellularly, fingolimod acts as a sphingosine-1-phosphate receptor antagonist which renders T and B cells insensitive to signals necessary for egress from lymphoid tissue.
• In animal models of multiple sclerosis, fingolimod resulted in reduced recirculation of autoaggressive lymphocytes to the central nervous system. Subsequently, in several large, randomized controlled trials, fingolimod was shown to reduce relapse rates and improve neuro-radiologic outcomes in adult patients with relapsing-remitting multiple sclerosis.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have had a heart attack, unstable angina, stroke or mini-stroke (transient ischemic attack or TIA) or certain types of heart failure in the last 6 months.
• 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.
• have a heart rhythm problem that needs treatment with certain medicines.
• are allergic to fingolimod or any of the ingredients in GILENYA.

What drug interactions can this medicine cause?

• GILENYA has not been studied in patients treated with drugs that prolong the QT interval (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin).
• Patients who use GILENYA and systemic ketoconazole concomitantly should be closely monitored, as the risk of adverse reactions is greater.
• Avoid the use of live attenuated vaccines during and for 2 months after treatment with GILENYA because of the risk of infection.
• Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with GILENYA.
• Because initiation of GILENYA treatment may result in an additional decrease in heart rate, concomitant use of drugs that slow the heart rate or AV conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers, such as diltiazem or verapamil) during GILENYA initiation may be associated with severe bradycardia or heart block.

Is this medicine FDA approved?

• Fingolimod was approved for use in relapsing multiple sclerosis in the United States in 2010 and was the first oral disease modifying agent approved in this condition.

How should this medicine be used?

• Obtain a cardiac evaluation in patients with certain preexisting conditions.
• Review results of a recent CBC.
• Prior to starting treatment with GILENYA (i.e., within 6 months), obtain serum transaminases (ALT and AST) and total bilirubin levels.
• Test patients for antibodies to varicella zoster virus (VZV) before initiating GILENYA; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with GILENYA.

Recommended dosage:

• In adults and pediatric patients 10 years of age and older weighing more than 40 kg, the recommended dosage of GILENYA is 0.5 mg orally once-daily.
• In pediatric patients 10 years of age and older weighing less than or equal to 40 kg, the recommended dosage of GILENYA is 0.25 mg orally once daily.
• Fingolimod doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefit.

First-Dose Monitoring (including reinitiation after discontinuation greater than 14 days and dose increases):

• Observe all patients for bradycardia for at least 6 hours; monitor pulse and blood pressure hourly. Electrocardiograms (ECGs) prior to dosing and at end of observation period required.
• Monitor until resolution if heart rate < 45 beats per minute (bpm) in adults, < 55 bpm in patients aged 12 years and above, or < 60 bpm in pediatric patients aged 10 to below 12 years, atrioventricular (AV) block, or if lowest postdose heart rate is at the end of the observation period.
• Monitor symptomatic bradycardia with ECG until resolved. Continue overnight if intervention is required; repeat first-dose monitoring for second dose.
• Observe patients overnight if at higher risk of symptomatic bradycardia, heart block, prolonged QTc interval, or if taking drugs with known risk of torsades de pointes.

Administration:

• Take GILENYA exactly as your doctor tells you to take it.
• Take GILENYA 1 time each day.
• If you take too much GILENYA, call your doctor or go to the nearest hospital emergency room right away.
• Take GILENYA with or without food.
• Do not stop taking GILENYA without talking with your doctor first.
• Call your doctor right away if you miss a dose of GILENYA. You may need to be observed by a healthcare professional for at least 6 hours when you take your next dose. If you need to be observed by a healthcare professional when you take your next dose of GILENYA you will have:
• an ECG before you take your dose
• hourly pulse and blood pressure measurements after you take the dose
• an ECG 6 hours after your dose
• If you have certain types of heart problems, or if you are taking certain types of medicines that can affect your heart, you will be observed overnight by a healthcare professional in a medical facility after you take your dose of GILENYA.
• If you have serious side effects after taking a dose of GILENYA, especially those that require treatment with other medicines, you will stay in the medical facility to be observed overnight. If you were observed overnight, you will also be observed for any serious side effects for at least 6 hours after you take your second dose of GILENYA.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As 0.25 mg hard capsules
• 0.5 mg hard capsules

This medicine is available in fallowing brand namesː

• GILENYA

What side effects can this medication cause?

The most common side effects of this medicine include:

• headache
• abnormal liver tests
• diarrhea
• cough
• flu
• inflammation of the sinuses (sinusitis)
• back pain
• stomach-area (abdominal) pain
• pain in arms or legs

GILENYA can cause serious side effects, including:

• Slow heart rate (bradycardia or bradyarrhythmia) when you start taking GILENYA
• Pregnancy
• Infections
• Progressive multifocal leukoencephalopathy (PML)
• A problem with your vision called macular edema
• swelling and narrowing of the blood vessels in your brain
• liver damage
• breathing problems
• severe worsening of multiple sclerosis after stopping GILENYA
• increased blood pressure
• basal cell carcinoma (BCC) and melanoma
• allergic reactions

What special precautions should I follow?

• GILENYA may increase the risk of infections, some serious in nature. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment and for 2 months after discontinuation. Do not start in patients with active infections.
• Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients with MS who received GILENYA. Withhold GILENYA at the first sign or symptom suggestive of PML.
• Fingolimod increases the risk of macular edema. Examine the fundus before and 3-4 months after treatment start. Diabetes mellitus and uveitis increase the risk.
• Clinically significant liver injury has occurred in patients treated with GILENYA. Obtain liver enzyme results before initiation and periodically during treatment. Closely monitor patients with severe hepatic impairment. Discontinue if there is evidence of liver injury without other cause.
• There have been rare cases of posterior reversible encephalopathy syndrome (PRES) reported in adult patients receiving GILENYA. If suspected, discontinue GILENYA.
• Respiratory Effects may occur with GILENYA. Evaluate when clinically indicated.
• GILENYA May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 2 months after stopping GILENYA.
• Monitor for development of severe increase in disability following discontinuation and begin appropriate treatment as needed.
• MS relapses with tumefactive demyelinating lesions on imaging have been observed during GILENYA therapy and after GILENYA discontinuation in the postmarketing setting. Consider when severe MS relapse occurs during treatment or after discontinuation. Obtain imaging and begin treatment as needed.
• Hypertension was reported as an adverse reaction in patients treated with GILENYA . Blood pressure should be monitored during treatment with GILENYA.
• The risk of basal cell carcinoma (BCC) and melanoma is increased in patients treated with GILENYA.
• Hypersensitivity reactions, including rash, urticaria, and angioedema have been reported with GILENYA in the postmarketing setting. GILENYA is contraindicated in patients with history of hypersensitivity to fingolimod or any of its excipients.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• bradycardia
• AV conduction blocks

Management of overdosage:

• In case of GILENYA overdosage, observe patients overnight with continuous ECG monitoring in a medical facility, and obtain regular measurements of blood pressure
• Neither dialysis nor plasma exchange results in removal of fingolimod from the body.

Can this medicine be used in pregnancy?

• Based on findings from animal studies, GILENYA may cause fetal harm when administered to a pregnant woman.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to GILENYA during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the GILENYA Pregnancy Registry by calling 1-877-598-7237, sending an email to gpr@quintiles.com

Can this medicine be used in children?

• Safety and effectiveness of GILENYA for the treatment of relapsing forms of multiple sclerosis in pediatric patients 10 to less than 18 years of age were established.
• Safety and effectiveness of GILENYA in pediatric patients below the age of 10 years have not been established.

What are the active and inactive ingredients in this medicine?

0.25 mg capsules

• Active ingredient: fingolimod
• Inactive ingredients: mannitol, hydroxypropylcellulose, hydroxypropylbetadex, magnesium stearate, gelatin, titanium dioxide, yellow iron oxide.

0.5 mg capsules

• Active ingredient: fingolimod hydrochloride
• Inactive ingredients: mannitol, magnesium stearate, gelatin, titanium dioxide, yellow iron oxide.

Who manufactures and distributes this medicine?

GILENYA is a registered trademark of Novartis, AG.

• Manufactured by: Novartis Pharma Stein AG Stein, Switzerland
• Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store GILENYA in the original bottle or blister pack in a dry place.
• Store GILENYA at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep GILENYA and all medicines out of the reach of children.

Multiple sclerosis drugs

Disease modifying agents

• Alemtuzumab
• Dimethyl Fumarate
• Fingolimod
• Glatiramer Acetate
• Interferon Beta
• Interferon Beta-1a
• Interferon Beta-1b
• Peginterferon Beta-1a
• Mitoxantrone
• Natalizumab
• Ocrelizumab
• Teriflunomide

Symptomatic Therapies

• Dalfampridine

• Dailymed label info on Fingolimod
• FDA Fingolimod

Fingolimod Resources
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