[Posted 08/29/2013]ISSUE: FDA is alerting the public that a patient in Europe diagnosed with possible multiple sclerosis (MS) has developed a rare and serious brain infection after taking the drug Gilenya (fingolimod). This is the first case of progressive multifocal leukoencephalopathy (PML), reported following the administration of Gilenya to a patient who had not previously received Tysabri (natalizumab), an MS drug associated with a higher risk of PML.
BACKGROUND: PML is a rare and serious brain infection caused by the John Cunningham (JC) virus that damages the fatty covering of the brain called myelin. PML usually causes death or severe disability. Gilenya is used to treat relapsing forms of MS, a nervous system disease that affects the brain and spinal cord. Novartis reports that approximately 71,000 patients worldwide have been treated with Gilenya.
RECOMMENDATION: Patients should not stop taking Gilenya without first discussing any questions or concerns with their health care professionals. FDA is providing this alert while continuing to investigate the PML case, and is working with Gilenya's manufacturer, Novartis, to obtain and review all available information about this occurrence. FDA will communicate its final conclusions and recommendations after the evaluation is complete.
For more information visit the FDA website at: Web Siteand Web Site.
Fingolimod is used to prevent episodes of symptoms and slow the worsening of disability in patients with relapsing forms (course of disease where symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do not function properly and people may experience weakness, numbness, loss of muscle coordination, and problems with vision, speech, and bladder control). Fingolimod is in a class of medications called sphingosine l-phosphate receptor modulators. It works by decreasing the action of immune cells that may cause nerve damage.
Fingolimod comes as a capsule to take by mouth. It is usually taken once a day with or without food. Take fingolimod at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take fingolimod exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Fingolimod may cause your heartbeat to slow, especially during the first 6 hours after you take your first dose. You will receive an electrocardiogram (ECG; test that records the electrical activity of the heart) before you take your first dose and again 6 hours after you take the dose. You will take your first dose of fingolimod in your doctor's office or another medical facility. You will need to stay at the medical facility for at least 6 hours after you take the medication so that you can be monitored. You may need to stay at the medical facility for longer than 6 hours or overnight if you have certain conditions that increase the risk that your heartbeat will slow or if your heartbeat slows more than expected or continues to slow after the first 6 hours. You may need to stay at a medical facility for at least 6 hours after you take your second dose if your heartbeat slows too much when you take your first dose. Tell your doctor if you experience dizziness, tiredness, chest pain, or slow or irregular heartbeat at any time during your treatment, especially during the first 6 hours after you take your first dose.
Fingolimod may help control multiple sclerosis but will not cure it. Do not stop taking fingolimod without talking to your doctor. If you do not take fingolimod for 1 day or longer during the first 2 weeks of treatment, for 1 week or longer in the third and fourth weeks of treatment or for 2 weeks or longer after the first month of treatment, talk to your doctor before you start taking it again. You may experience slowed heartbeat when you start taking fingolimod again, so you will need to restart the medication in your doctor's office.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with fingolimod and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking fingolimod,
- tell your doctor and pharmacist if you are allergic to fingolimod, any other medications, or any of the ingredients in fingolimod capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor if you are taking medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), dronedarone (Multaq), procainamide, quinidine (Quinaglute, others), and sotalol (Betapace). Your doctor will probably tell you not to take fingolimod if you are taking one or more of these medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take during your treatment with fingolimod and for 2 months after your treatment. Be sure to mention any of the following: beta-blockers such as atenolol (Tenormin), carteolol (Cartrol), labetalol (Normodyne, Trandate), metoprolol (Lopressor), nadolol (Corgard), propranolol (Inderal), and timolol (Blocadren); calcium channel blockers such as diltiazem (Cardizem, Dilacor) and verapamil ; citalopram (Celexa); chlorpromazine; digoxin (Lanoxin); erythromycin (ERY-C, Ery-Tab, PCE); haloperidol; ketoconazole (Nizoral); medications to control the immune system; medications for cancer, heart problems, or high blood pressure. and methadone (Dolophine, Methadose).Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with fingolimod, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have or have had any of these conditions in the last six months: fainting, heart attack, angina (chest pain), stroke or mini-stroke, or heart failure. Also tell your doctor if you have long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death) or irregular heart rhythm, Your doctor may tell you not to take fingolimod.
- tell your doctor if you have ever fainted, if you currently have a fever or other signs of infection, if you have an infection that comes and goes or that does not go away, and if you have or have ever had diabetes; sleep apnea (condition in which you briefly stop breathing many times during the night) or other breathing problems; high blood pressure; uveitis (inflammation of the eye); a slow heartbeat; low levels of potassium or magnesium in your blood; or liver, or kidney disease.
- tell your doctor if you have never had chicken pox and have not received the chicken pox vaccine. Your doctor may order a blood test to see if you have been exposed to chicken pox. You may need to receive the chicken pox vaccine and then wait one month before beginning your treatment with fingolimod.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You should use birth control to prevent pregnancy during your treatment and for 2 months after your treatment. If you become pregnant while taking fingolimod, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking fingolimod.
- do not have any vaccinations during your treatment with fingolimod or for 2 months after your treatment without talking to your doctor.
Unless your doctor tells you otherwise, continue your normal diet.
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and call your doctor before you take the next dose. You may need to be monitored as you restart your medication. Do not take a double dose to make up for a missed one.
Fingolimod may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- back pain
- numbness, burning, or tingling in the hands or feet
- dry, peeling, or itchy skin
- hair loss
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- slow or pounding heartbeat
- chest pain
- excessive tiredness
- sore throat, fever, chills, cough, and other signs of infection
- eye pain
- blurriness, shadows, or a blind spot in the center of your vision
- sensitivity to light
- unusual color to your vision
- shortness of breath
- loss of appetite
- stomach pain
- yellowing of the skin or eyes
- dark urine
Fingolimod may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include:
- chest tightness or discomfort
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests and eye exams and will monitor your blood pressure before and during your treatment to be sure that it is safe for you to begin taking or continue to take fingolimod.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking fingolimod.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: September 15, 2013.