• Gilenya is a brand (trade) name for fingolimod which may be used to treat multiple sclerosis.
• Gilenya (fingolimod) is thought to work by blocking the migration of lymphocytes (a type of immune cell) from the lymph nodes into the bloodstream. Gilenya (fingolimod) is derived from myriocin (ISP-1), a natural immunosuppressant, and metabolite of the fungus Isaria sinclairii. It was first made by Yoshitomi Pharmaceuticals in 1992 from ISP-I through chemical modification.
• Gilenya belongs to the class of medicines known as selective immunosuppressants.

• Gilenya is an immunosuppressant that may be used for the treatment of relapsing multiple sclerosis (MS) in adults, and children aged 10 years and older.
• Gilenya reduces nerve inflammation and subsequent damage.
• The dose of Gilenya is the same for adults and children over the age of 10 who weigh more than 40kg: 0.5 mg once daily. For those under 40kg, the dose should be reduced to 0.25mg once daily.
• Gilenya is taken by mouth (orally) once a day.
• May be taken with or without food.
• No dosage adjustment is needed for people with mild-to-moderate liver disease.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Abdominal pain, an increase in blood triglycerides, an increased risk of basal cell carcinoma (2%) and skin papilloma (3%), an increased risk of infections, such as the flu, sinusitis, bronchitis, herpes zoster, and tinea versicolor; back pain or other pain; blood disorders; blurred vision; bradycardia (a slow heart rate); cough; diarrhea; hair loss; headache; high blood pressure; liver enzyme elevations and liver injury; migraine; nausea; shortness of breath; weakness.
• Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients with MS who received Gilenya. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that often leads to death or severe disability. Posterior reversible encephalopathy syndrome (PRES) and respiratory effects have also been reported.
• Hair loss is an uncommon side effect of Gilenya. In clinical trials, 3% of people who had hair loss were taking Gilenya, compared with 2% of people taking a placebo.
• Gilenya should not be given to people who have experienced a heart attack (myocardial infarction) in the last 6 months, or with various other cardiovascular conditions such as unstable angina, stroke, or severe heart failure; with a baseline QTc interval ≥ 500 msec; with cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs; with a previous allergic reaction to fingolimod or any of the excipients in Gilenya.
• Obtain a CBC before initiating treatment with Gilenya. Gilenya causes a dose-dependent reduction in peripheral lymphocyte count to 20%–30% of baseline values via redistribution in secondary lymphoid organs. This means that peripheral blood lymphocyte counts cannot be utilized to evaluate lymphocyte levels in a patient treated with Gilenya. Within 6 months of starting Gilenya obtain serum transaminases (ALT and AST) and total bilirubin levels.
• A full cardiac evaluation should be conducted before starting Gilenya in those with pre-existing conditions, such as ischemic heart disease, a history of myocardial infarction, or cerebrovascular disease. Conduct a full medication review for other medications that may also slow the heart rate and consider modifying treatment before initiating Gilenya.
• Gilenya does not cure MS, it only decreases the frequency of relapses.
• Gilenya will suppress the immune system and will reduce a person's ability to fight infection. This ability will be further compromised if the person is also taking other drugs that suppress the immune system, such as chemotherapy agents, immune-modulating therapies, or other immunosuppressants. This immune-suppressing effect will persist for up to two months after stopping Gilenya treatment. Review all other immune-suppressing medications before initiating Gilenya, and be aware of those with a long half-life whose effects may persist for weeks after discontinuation, such as natalizumab, teriflunomide, or mitoxantrone. Life-threatening and fatal infections have occurred in association with Gilenya.
• Gilenya will also reduce the immune response to live vaccines, such as MMR and varicella vaccines. All vaccines should be up to date before Gilenya is even started. Test patients for antibodies to varicella zoster virus (VZV) before initiating Gilenya and vaccinate all antibody-negative patients with VZV vaccination before commencing treatment with Gilenya. All pediatric patients should complete all immunizations per current immunization guidelines before initiating Gilenya therapy, if possible.
• Gilenya can increase the risk of macular edema. Perform an eye examination before starting treatment, again 3 to 4 months after starting treatment, and again at any time after a patient reports visual disturbances while on Gilenya therapy.
• Gilenya can cause bradycardia, particularly on first dose initiation. The maximum decline in heart rate generally occurs within 6 hours of the first dose and recovers, although not to baseline levels, by 8 to 10 hours post dose. There is also a second period of heart rate decrease within 24 hours because of physiological diurnal variation. In trials, symptomatic bradycardia following the first dose was reported in 0.6% of patients receiving Gilenya 0.5 mg and in 0.1% of patients on a placebo. Most were asymptomatic, but some experienced hypotension, dizziness, fatigue, palpitations, and/or chest pain.
• The first dose of Gilenya should be initiated in a setting that can appropriately manage people for symptomatic bradycardia (a slow heartbeat) for 6 hours (sometimes longer). Before the first dose and at the end of the observation period an ECG should be obtained in all patients. During the 6 hours, the patient's pulse and blood pressure should be taken every hour. Continue monitoring after the 6 hours if any of the following are present: a heart rate less than 45 bpm in adults, less than 55 bpm in pediatric patients 12 years of age and older, or less than 60 bpm in pediatric patients 10 or 11 years of age; the heart rate taken 6 hours postdose is at the lowest value suggesting that the maximum pharmacodynamic effect on the heart may not have occurred; the ECG obtained 6 hours postdose shows new onset second degree or higher AV block. Continue monitoring until symptoms have resolved if no pharmacological treatment is required, or if treatment is required, continue monitoring overnight and repeat 6-hour monitoring after the second dose. Some patients may require continuous ECG monitoring overnight (see product information for details).
• First-dose monitoring for bradycardia is required by all patients if Gilenya is stopped with an interruption of one day or more during the first two weeks or during weeks 3 and 4 of treatment, after treatment interruptions of more than 7 days. Thereafter, first-dose monitoring is required for interruptions of longer than 14 days.
• Gilenya is expensive. Gilenya 0.5mg costs around $302 per capsule, or $9053 for a supply of 30 capsules. however, 96 to 99% of people with commercial or private health insurance or who are eligible for Medicare or Medicaid are covered for Gilenya. Co-pay assistance is also available through the GILENYA Medical Co-Pay Support Program. Most people pay nothing. The cost of pre-tests and first observations may also be covered.
• Gilenya interacts with many medications, particularly those with immune-lowering effects or those that slow the heart.
• In people with kidney disease, the blood levels of some Gilenya metabolites may be increased up to 13-fold. There has not been enough research to determine what effects this has.
• Gilenya may cause harm to a developing baby and animal studies have reported developmental toxicity at doses less than the recommended human dose. All females of reproductive potential should use effective contraception to avoid pregnancy during and for 2 months after stopping Gilenya treatment.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• You can take Gilenya with or without food, but you should try and take it at the same time each day. If you miss a dose, take it as soon as you remember. If it is close to your next dose, miss that dose do not double up your dosage. If you miss a dose in your first two weeks of taking Gilenya, contact your doctor as they may need to monitor your heart rate again.
• Gilenya can slow your heart rate, and this is more likely to happen with the very first dose of Gilenya, or if you miss a dose during the first two weeks of treatment, and then start taking Gilenya again.
• While you are taking Gilenya you are at an increased risk of infections, because Gilenya lowers your immune response. Some vaccinations may need to be avoided during treatment with Gilenya and for two months after stopping it. Take care to avoid people who are unwell and protect yourself from injury. See your doctor immediately if you develop any signs of an infection which may include fever, pain, swelling, redness, or a discharge.
• Although Gilenya is expensive, most people pay nothing because 96 to 99% of people with commercial or private health insurance or who are eligible for Medicare or Medicaid are covered for Gilenya. Co-pay assistance is also available through the GILENYA Medical Co-Pay Support Program. The cost of pre-tests and first observations may also be covered. For those experiencing financial hardship or with no prescription coverage, The Novartis Patient Assistance Foundation, Inc. (NPAF) is committed to providing access to Novartis medications for those most in need. Call the Gilenya Go Program at 1 800-445-3692.
• Do not stop taking Gilenya without talking to your prescriber first. In 2018, the FDA issued a warning stating that there is a possibility for some people that their MS may worsen significantly on stopping Gilenya. This worsening is rare but could result in permanent disability. The increase in disability generally occurred within 12 weeks after stopping Gilenya but was reported up to 24 weeks after Gilenya's discontinuation. Reasons for stopping may include intolerable adverse drug reactions, planned or unplanned pregnancy, or because the medicine is not working.
• Gilenya can increase your risk of macular edema and you should have an eye test before starting treatment with Gilenya, 3 to 4 months after starting treatment, and then regularly thereafter.
• See your doctor if you experience any unusual or worrying side effects, such as abdominal pain, fainting, heart palpitations, a rash, nausea, vomiting, shortness of breath, fever, or vision problems. Gilenya can also increase your risk of developing progressive multifocal leukoencephalopathy (PML), a serious viral infection, and symptoms may include progressive weakness on one side of the body, limb clumsiness, vision disturbance, changes in thinking, memory, and orientation leading to confusion and personality changes. See your doctor immediately if any of these symptoms happen to you.
• Gilenya is not safe to use during pregnancy and is not recommended during breastfeeding. If you are of child-bearing potential you may have to undertake a pregnancy test before starting Gilenya and use reliable contraception while taking it. If you inadvertently become pregnant during Gilenya treatment or within 2 months of stopping it, tell your doctor straight away.
• Gilenya can increase your risk of developing skin cancer including basal cell carcinomas and melanomas. Protect your skin from sunlight and wear protective clothing and use sunscreen with a high sun protection factor. Tell your doctor if you have any changes in the appearance of your skin, including changes in a mole or sores that do not heal.
• Gilenya capsules should be kept at room temperature 20ºC to 25ºC (68ºF-77ºF) and protected from moisture.

• The annualized relapse rate was significantly lower in patients treated with Gilenya than in patients who received a placebo an inactive treatment) in a study that enrolled over 1200 people with MS. After two years, 70% of people reported no relapse compared with 46% of those taking a placebo. The mean (median) number of new or newly enlarging T2 lesions over 24 months was 2.5 with Gilenya and 9.8 with placebo. Other studies have shown similar results.
• Gilenya lasts in the blood for a long time, and lymphocyte counts take 1 to 2 months to return to baseline. After stopping therapy, a person’s immune system will remain compromised for up to two months after stopping Gilenya treatment, which means their risk of infection will remain increased.
• Research has shown Gilenya decreases blood lymphocytes to approximately 60% of baseline within four to six hours of the first dose. With continued dosing, the lymphocyte count continued to decrease eventually reaching a low point (called the nadir count) of blood lymphocyte count that corresponded to 30% of baseline or 500 cells/mcL after two weeks.
• Some studies have reported nadir counts of < 200 cells/mL in patients on at least one occasion.
• Gilenya is known as a disease-modifying drug and it reduces the number of relapses of multiple sclerosis (MS) by about half (50%). Any relapses that do happen should be less severe. It takes approximately two weeks of dosing for Gilenya to reach its maximum effect, which is a lymphocyte count of 30% of baseline or around 500 cells/mcL.
• There is a risk that your MS symptoms may worsen if you stop taking Gilenya. This effect is rare, with 35 known cases documented over 8 years. Recovery varied. 17 patients had partial recovery, 8 experienced permanent disability or no recovery, and 6 eventually returned to the level of disability they had before or during Gilenya treatment. Several patients who were able to walk without assistance before discontinuing Gilenya progressed to needing wheelchairs or becoming bedbound.
• Dosages of Gilenya higher than 0.5mg once a day are associated with more side effects with little extra benefit.

Medicines that interact with Gilenya may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Gilenya. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Gilenya interacts with over 500 medications; the majority of these interactions are considered major. Common medications that may interact with Gilenya include:

• antibiotics such as azithromycin, ciprofloxacin, or norfloxacin
• antineoplastics, such as capecitabine, or cyclophosphamide
• antipsychotics, such as clozapine, aripiprazole, or haloperidol
• astemizole
• biologics, such as adalimumab, etanercept, golimumab, or infliximab
• busulfan
• corticosteroids (such as prednisone or dexamethasone)
• heart medications, particularly those that also slow the heart rate, such as beta-blockers (eg, atenolol, sotalol), digoxin, amiodarone, or flecainide (may be associated with severe bradycardia or heart block)
• herbals, such as black cohosh or brewer's yeast
• HIV medications, such as atazanavir or zidovudine
• hydroxychloroquine
• immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• interferon
• ketoconazole (may increase blood levels of Gilenya up to 1.7 fold. Monitor)
• lithium
• live vaccines and some other vaccines, such as BCG, cholera, measles, hepatitis b vaccines, yellow fever, or live influenza vaccines (Gilenya reduces the immune response to vaccination if vaccines are given within 2 months of a Gilenya dose)
• methotrexate
• oxytocin
• probiotics, such as lactobacillus
• promethazine
• quinine
• tamoxifen.

There is a risk Gilenya may exacerbate the QT-prolonging effects of some medications, such as citalopram, chlorpromazine, haloperidol, methadone, or erythromycin. Initiation of Gilenya treatment results in a decreased heart rate which may prolong the QT interval. Monitor all patients already on QT-prolonging drugs with a known risk of torsades de pointes overnight with continuous ECG in a medical facility when starting Gilenya.

Gilenya may have additive immune-suppressing effects when given with any other medications such as anticancer drugs, immune-modulating, or immunosuppressive therapies, which may increase a person's risk for infection. Take this into account when switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide, or mitoxantrone.

Strong enzyme inducers, such as carbamazepine, rifampicin, phenytoin, phenobarbital, and St. John’s wort, have been shown to decrease Gilenya blood concentrations by approximately 40%. The clinical impact of this decrease is unknown.

Note that this list is not all-inclusive and includes only common medications that may interact with Gilenya. You should refer to the prescribing information for Gilenya for a complete list of interactions.