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Fingolimod (Gilenya®) Information for People Affected by MS

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April 17, 2012
February 10, 2012

The Multiple Sclerosis Emerging Therapies Collaborative includes the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), the MS Coalition, the American Academy of Neurology, and the VA Multiple Sclerosis Centers of Excellence East and West.

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What is the medication?
Generic: Fingolimod
Brand name: Gilenya
First oral medication (taken by mouth) approved by the Food and Drug Administration (FDA) to modify disease activity in multiple sclerosis (MS)
Has the US Food and Drug Administration (FDA) approved the medication?
Yes – A 0.5-mg daily dose was approved by the FDA on September 21, 2010.
If so, what is the recommended use in MS, and for whom is the medication recommended?
  • The medication is approved to reduce the frequency of relapses (also called exacerbations or attacks) and to delay physical disability. It is recommended for people with relapsing forms of MS.
  • Studies are currently being done to find out if this medication can also help people with primary-progressive MS.
What studies did the FDA look at when deciding whether to approve this medication? What were the results of these studies?
Two large trials have been published so far:
  • The FREEDOMS trial (Kappos L, et al. N Engl J Med. 2010;362:387-401)

    What was the design of the study?
    Three groups of people took part in this two-year study – a low-dose (0.5-mg) fingolimod group, a higher-dose (1.25-mg) fingolimod group, and a group that took a placebo (a capsule without active medication).

    What questions was the study trying to answer?
    This study was designed to answer several questions, including:
    • Do people taking fingolimod have fewer relapses (exacerbations or attacks) over the two-year study than the group taking the placebo?
    • Is the risk of disability progression over the two-year study period lower in people taking fingolimod than in those who are taking placebo?
    • Do people taking fingolimod have fewer new lesions (damaged areas related to MS) on magnetic resonance imaging (MRI) scans over the two-year study than people taking placebo?
    • Do people taking fingolimod develop less brain tissue loss or shrinkage over the two-year study than people taking placebo?
    • Does the group taking the low dose of fingolimod have different results or side effects than the group taking the high dose of fingolimod?

    What were the results of the study?
    • The annual relapse rate was 0.18 for the group taking the 0.5-mg dose and 0.40 for those on placebo. This means that over the two years if the trial the group taking fingolimod had a 54% lower risk of relapse than the group taking the placebo.
    • The risk of disability progression was 30% lower over the two years of the trial in people taking the 0.5-mg dose of fingolimod than in people taking the placebo.
    • The people taking fingolimod had fewer new lesions and developed less brain tissue loss, as shown on their MRI scans, than the group taking placebo.
    • The group taking the low dose of fingolimod and the group taking the high dose of fingolimod did equally well, but the higher-dose group had more side effects, including two deaths. These findings led to the FDA's decision to approve only the 0.5-mg dose of fingolimod.

  • The TRANSFORMS trial (Cohen J, et al. N Engl J Med. 2010;362:402-415)

    What was the design of the study?
    Three groups of people took part in this 12-month trial. All of them had a relapse during the year before entering the study, many while taking an injectable disease modifying treatment for MS. During the study, one group took a weekly injection of interferon beta-1a (Avonex®) and a daily capsule containing a placebo. One group took the daily 0.5-mg dose of fingolimod and a weekly injection containing a placebo. One group took the daily 1.25-mg dose of fingolimod and a weekly injection of placebo.

    What questions was the study trying to answer?
    This study was designed to answer several questions, including:
    • Do people taking fingolimod have fewer relapses over the one-year study than people taking interferon beta-1a (Avonex)?
    • Do people taking fingolimod have fewer new lesions (spots) on their MRI over the one-year study than people taking interferon beta-1a (Avonex)?
    • Is the risk of disability progression over the one-year study period lower in people taking fingolimod than in people taking interferon beta-1a (Avonex)?

    What were the results of the study?
    • The relapse rate during the one-year study was 0.16 per year for the 0.5-mg fingolimod group and 0.33 per year for the group taking Avonex. This means that the group taking fingolimod had a 52% lower risk of having a relapse during the study period than the group taking interferon beta-1a (Avonex).
    • 82.5% of people taking the 0.5-mg dose of fingolimod and 70% of people taking interferon beta-1a had no relapses during the 12 months of the study.
    • The group taking the 0.5-mg dose of fingolimod had fewer signs of disease activity on MRI than the group taking Avonex.
    • There was no difference among the groups in the risk of disease progression over the course of the 12-month study.
How does the medication work?
Fingolimod appears to prevent some potentially damaging T cells (types of white blood cells called T-lymphocytes) from leaving the lymph nodes. The result is that there are fewer T cells traveling into the central nervous system (CNS - the brain and spinal cord) to do damage. It is not known yet whether fingolimod helps or protects the cells in a person's CNS.
How is this medication taken? What is the dosage and how often is it taken?
Fingolimod is taken once a day by mouth in capsule form. The dose of the medication is 0.5 mg.
Can this medication be used with other medications?
  • Disease-modifying Therapies:
    • Has this medication been tested in combination with other medications?
      • No studies have been done to look at the use of fingolimod in combination with other disease-modifying therapies.
      • The FDA has suggested caution when switching from a long-acting therapy such as natalizumab or mitoxantrone to fingolimod. If you are currently taking one of these medications, your doctor will determine if a switch is safe or appropriate for you. See Product Insert
  • Other Medications
    • Can fingolimod be taken with other medications a person is taking to manage MS symptoms or other medical problems?
      • Certain medications are known to interact with fingolimod. These include medications that contain quinidine, such as Neudexta®, a combination of dextromethorphan and quinidine that is approved for treating uncontrollable laughing and/or crying (pseudobulbar affect) in people with MS. Other medications that might interact with fingolimod include beta blockers (a type of heart medication) and some medications that are used to treat fungal infections.
      • Live vaccines should not be taken by someone who is taking fingolimod or within two months after a person stops taking fingolimod. The reason for this is that live vaccines can increase a person's risk of infection.
      • Inactivated (killed) vaccines (such as the seasonal flu vaccine) may not be as effective while a person is taking fingolimod or for 2 months after treatment with fingolimod is stopped.
What results can a person expect from this medication?
  • Fingolimod does not cure MS or make the symptoms of MS go away.
  • Fingolimod was shown in the clinical trials to reduce the rate of relapses, reduce the disease activity (as shown on MRI scans), and slow the progression of disability.
  • No data are available yet to show whether fingolimod is effective in the long term.
  • Only one comparison trial (the TRANSFORMS trial – see p. 2) has been done so far. More comparison trials must be done to determine is fingolimod is more effective that the other approved MS disease-modifying therapies.
What are the possible short-term side effects of this medication?
  • The most commonly-reported side effects of fingolimod are headache, flu, diarrhea, back pain, abnormal liver tests, and cough.
  • Fingolimod can cause a person's heart rate to slow, particularly right after the first dose. The heart rate will be lowest approximately six hours after the first dose, which may cause the person to feel dizzy or tired. The heart rate will generally return to normal within one month.
  • During the course of the two-year FREEDOMS trial two individuals on the higher (1.25-mg) dose of the medication died from herpes virus infections. One patient who had never had chicken pox was infected with the herpes virus that causes chicken pox. The other person was infected with a different kind of herpes virus that caused a brain infection.
Can long-term health problems occur from use of this medication?
  • The FDA's labeling information for fingolimod lists some warnings about health problems that can occur with the use of fingolimod:
    • Increased risk of infections. In clinical trials, a small number of serious herpes infections occurred, including two deaths from herpes infections that occurred in people taking the 1.25-mg dose rather than the 0.5-mg dose that the FDA has now approved.
    • Macular edema (swelling of the center of the retina inside the eye)
    • Decrease in lung function
    • Slight increase in blood pressure
    • Increases in liver enzymes (which indicate liver injury)
  • The long-term safety of fingolimod is unknown at this time.
Is training recommended or required for people who are starting this treatment?
There is no specific training required of either provider or patient before beginning fingolimod treatment.
What is known about the effect of this medication on reproduction?
Fingolimod is Pregnancy Category C, which means that animal studies have shown that it may cause harm to the unborn baby. It is recommended that women use effective birth control while taking fingolimod and for two months after stopping the medication.
Does this medication interact or interfere with oral contraceptives (birth control pills)?
Fingolimod is not known to interact with oral contraceptives.
Has the FDA recommended or required a safety-monitoring program?
  • The FDA has required Novartis to create a registry that will follow 5000 patients for five years to track any significant safety problems that may occur.
  • Novartis has created a pregnancy registry in order to follow the pregnancies of any women who accidentally become pregnant while taking fingolimod or within two months after stopping the medication. Since all women in the clinical trials were required to be using birth control, this is the most effective way to learn about the impact of fingolimod on a woman's health during pregnancy and on her unborn baby.
Does the FDA recommend or require that people taking this medication be monitored for safety concerns?
The FDA has recommended that clinicians and patients take certain steps for safety purposes. These steps are intended to lower health risks
  • Prior to starting treatment, a person should be evaluated for heart, lung, liver, and eye problems.
  • A person with no history of chicken pox should be given a blood test for antibodies to determine if he or she has ever been exposed to the varicella zoster virus. If the test indicates that the person has not previously been exposed, the FDA recommends that the varicella zoster vaccination be considered at least one month prior to starting treatment with fingolimod.
  • A person's pulse and blood pressure should be measured before the first dose. The person should remain in a medical facility for six hours following the first dose so that she or he can be observed for changes in heart rate. If a drop occurs that is significant enough to cause symptoms, those symptoms should be managed before the person leaves the medical facility.
  • Blood pressure should be monitored on a regular basis while a person is taking fingolimod.
  • People should have their eyes examined 3-4 months after starting treatment and any time that they experience visual symptoms.
  • A person who develops breathing problems while taking fingolimod should report them to the doctor so an evaluation can be done.
  • A person who develops symptoms of liver problems should report them to the doctor so an evaluation can be done. These symptoms might include yellowing of the skin and whites of the eyes; dark urine; light-colored bowel movements; nausea and vomiting; diarrhea; loss of appetite.
How long can a person safely take this medication?
There are no recommended limits for treatment with fingolimod.
What happens if a person stops taking fingolimod?
  • If a person stops this medication, what other treatment options are available for patients after being treated with fingolimod?
    After taking fingolimod a person may take any of the other disease-modifying therapies.
  • After stopping fingolimod, how long would a person have to wait before starting a different medication?
    The answer to this question is not known. The numbers of certain types of cells in the body generally return to their normal levels within two months of stopping fingolimod. This means that healthcare providers will probably recommend waiting at least two months before starting another disease-modifying therapy.
  • What would a person do in the meantime?
    While waiting to begin treatment with another medication, a patient should work with his or her healthcare provider on a plan to manage symptoms.
  • Are there any risks associated with suddenly stopping the use of fingolimod?
    The answer to this question is not known. It is important for people to talk with their healthcare provider before suddenly stopping any medication that has been prescribed for them.
How can a person tell if the medication is not working?
Fingolimod does not treat long-standing symptoms. This means that symptoms a person has had for some time are likely to continue even if the medication is working. It is possible for relapses to occur even if the person is taking fingolimod as prescribed. If a sudden worsening of symptoms occurs, the person should see her or his healthcare provider for further evaluation.
Is the manufacturer/distributor offering any financial assistance program for patients?
Financial assistance is available from Novartis. Call 1-877-408-4974 for information about their financial assistance program.
Are there any special considerations for this medication?
People with relapsing forms of MS would be considered appropriate candidates for this therapy.


Julie Cox, Gay Falkowski, Cindy Richman
Rosalind Kalb, PhD

Fingolimod (Gilenya) for Clinicians and Patients Affected by MS – Posted on February 10, 2012

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Click here to read the complete Gilenya information for clinicians and for people affected by MS.

Following the report on January 20, 2012 of 11 deaths among patients who received fingolimod (Gilenya) outside of the clinical trials, the European Medicines Agency (EMA) announced a review of the medication. This review is separate from the investigation currently underway by the U.S. Food and Drug Administration (FDA). The FDA issued a statement in December, 2011 concerning a patient who died within 24 hours of receiving a first dose of the medication.

According to Novartis Pharmaceuticals, more than 33,000 people have received fingolimod to date. Although little is known at this time about the 11 reported deaths, they appear to be related to cardiac events. Until the EMA and FDA have completed their reviews, it is impossible to know what role fingolimod may have played in the deaths.

While their review is under way, the EMA has recommended to healthcare professionals in Europe that they increase patient monitoring for the first dose of fingolimod. The recommendations include:

  • Electrocardiogram (ECG) monitoring before treatment and then continuously during the first six hours following the first dose
  • Measurement of blood pressure and heart rate every hour during the six-hour observation period
  • After six hours, any patients with clinically important heart-related effects, such as bradycardia (a slow heart rate) or atrioventricular block (a problem with the conduction of electricity in the heart), should continue to be managed and monitored until their condition has improved.

Pending further investigation, the FDA recommends that healthcare professionals who prescribe Gilenya continue to follow the recommendations on the approved label. The FDA further states that people who are currently taking Gilenya should not stop taking it without talking to their prescriber.

The Emerging Therapies Collaborative will continue to post updated information as it becomes available.

Fingolimod (Gilenya) for Clinicians and Patients Affected by MS – Posted on April 17, 2012

In April, 2012, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) revised the prescribing information for fingolimod, based on independent safety reviews initiated by the agencies after deaths were reported among patients taking fingolimod. The revised prescribing information defines who should avoid using this multiple sclerosis (MS) therapy based on pre-existing medical conditions, and alters the recommended testing and heart monitoring that occur when the first dose is given.

In the United States, the prescribing information update includes the following:

First-Dose Monitoring

  • After the first dose of fingolimod, the heart rate decrease starts within an hour, and the Day 1 nadir generally occurs within approximately 6 hours, although the nadir can be observed up to 24 hours after the first dose in some patients.
  • The first dose of fingolimod should be administered in a setting in which adequate resources are available to manage symptomatic bradycardia. All patients should be given an electrocardiogram prior to the first dose and at the end of the 6-hour observation period. During the observation period, monitor all patients with hourly pulse and blood pressure measurement for signs of bradycardia.
  • If any of the following occur, additional observation should be instituted until the finding has resolved:
    • The heart rate 6 hours post-dose is <45 bpm
    • The heart rate 6 hours post-dose is at the lowest value post-dose (suggesting that the maximum pharmacodynamics effect on the heart may not have occurred)
    • The ECG 6 hours post-dose shows new onset second degree or higher AV block or a QTc interval greater than or equal to 500 msec.
    If post-dose symptomatic bradycardia occurs:
    • Initiate appropriate management
    • Begin continuous ECG monitoring
    • Continue observation until the symptoms have resolved
    If a patient requires pharmacologic intervention for symptomatic bradycardia:
    • Provide continuous overnight ECG monitoring in a medical facility
    • Repeat the first-dose monitoring strategy after the second dose of fingolimod
  • Patients with some pre-existing conditions (e.g., ischemic heart disease, history of myocardial infarction, congestive heart failure, history of cardiac arrest, cerebrovascular disease, history of symptomatic bradycardia, history of recurrent syncope, severe untreated sleep apnea, AV block, sino-atrial heart block) may be unable to tolerate fingolimod-induced bradycardia or experience serious rhythm disturbances after the first dose. Prior to treatment with fingolimod, patients with any of these conditions should have a cardiac evaluation by a physician appropriately trained to conduct such evaluation [See Commentary] and, if treated with fingolimod, should be monitored overnight with continuous ECG in a medical facility after the first dose. Fingolimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart failure)
  • Since initiation of fingolimod treatment results in decreased heart rate and may prolong the QT interval, patients with a prolonged QT interval (>450 msec males, >470 msec 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 Tosades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin), should be monitored overnight with continuous ECG in a medical facility.
  • Experience with fingolimod is limited in patients receiving concurrent therapy with drugs that slow heart rate (e.g., beta blockers, heart-rate-lowering calcium channel blockers such as diltiazem or verapamil, or digoxin). Because the initiation of fingolimod is associated with slowing of the heart rate, concomitant use of these drugs may be associated with severe bradycardia or heart block. The physician prescribing the heart-rate-lowering medication should consider switching to non-heart-rate-lowering drugs before fingolimod is initiated. In patients who cannot switch, overnight continuous ECG monitoring after the first dose is recommended.
  • Clinical data indicate that the effects of fingolimod on heart rate are maximal after the first dose – although milder effects on heart rate may persist for an average of 2-4 weeks after initiation of therapy – at which time heart rate generally returns to baseline. Physicians should continue to be alert to patient reports of cardiac symptoms.


Re-initiation of Therapy Following Discontinuation

  • If fingolimod is discontinued for more than 14 days after the first month of treatment, the effects on heart rate and AV conduction may recur on reintroduction of fingolimod treatment. Therefore, the same first-dose monitoring should be repeated.
  • Within the first 2 weeks of treatment, first-dose procedures are recommended after interruption of one day or more.
  • During week 3 and 4 of treatment, first-dose procedures are recommended after treatment interruption of more than 7 days.



  • Patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure
  • Mobitz Type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker
  • Baseline QTc interval >500 ms
  • Treatment with Class Ia or Class III anti-arrhythmic drugs


Warnings and Precautions

Bradyarrhythmia and Atrioventricular Blocks

Because of a risk for bradyarrhythmia and atrioventricular (AV) blocks, patients should be monitored during initiation of treatment with fingolimod.

Reduction in heart rate

  • After the first dose of fingolimod, the heart rate decrease starts within an hour. On Day 1, the maximal decline in heart rate generally occurs within 6 hours and recovers, although not to baseline levels, by 8-10 hours post-dose.
  • Because of physiological diurnal variation, there is a second period of heart rate decrease within 24 hours after the first dose. In some patients, heart rate decrease during the second period is more pronounced than the decrease observed in the first 6 hours.
  • Heart rates below 40 beats per minute were rarely observed. Adverse reactions of symptomatic bradycardia following the first dose were reported in 0.5% of patients receiving fingolimod 0.5 mg, but in no patient on placebo.
  • Patients who experienced bradycardia were generally asymptomatic, but some patients experienced hypotension, dizziness, fatigue, palpitations, and chest pain that usually resolved within the first 24 hours on treatment.
  • Following the second dose, a further decrease in heart rate may occur when compared with the heart rate prior to the second dose, but this change is of a smaller magnitude than that observed following the first dose. With continued dosing, the heart rate returns to baseline within one month of chronic treatment.


Blood Pressure Effects

  • Blood pressure should be monitored during treatment with fingolimod.
    • In MS clinical trials, patients treated with fingolimod 0.5 mg had an average increase of approximately 2 mmHg in systolic pressure, and approximately 1 mmHg in diastolic pressure, first detected after approximately 1 month of treatment initiation, and persisting with continued treatment.
    • In controlled studies involving 854 MS patients on fingolimod 0.5 mg and 511 MS patients on placebo, hypertension was reported as an adverse reaction in 5% of patients on fingolimod 0.5 mg and in 3% of patients on placebo.


Post-Marketing Experience

  • In the post-marketing setting, third-degree AV block and AV block with junctional escape have been observed during the first-dose 6-hour observation period.
  • Isolated delayed-onset events, including transient asystole and unexplained death, have occurred within 24 hours of the first dose. These events were confounded by concomitant medications and/or pre-existing disease; the relationship to fingolimod is uncertain.
  • Cases of syncope were also reported after the first dose.



It is the recommendation of the Emerging Therapies Collaborative Work Group that the pre-treatment evaluation of patients with pre-existing cardiac conditions be done by a cardiologist.

The Emerging Therapies Collaborative is proud to be a source of information about multiple sclerosis. Our comments are based on published data and expert opinion, but do not represent individual therapeutic recommendations or prescriptions. For specific information and advice, consult your physician.
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Last Updated on Monday, 15 April 2013 16:06