Siponimod

Siponimod is used to prevent episodes of symptoms and slow the worsening of disability in adults with relapsing-remitting 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), including clinically isolated syndrome (CIS; first nerve symptom episode that lasts at least 24 hours), relapsing-remitting disease (course of disease where symptoms flare up from time to time), or active secondary progressive disease (later stage of disease with continuous worsening of symptoms). Siponimod 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.

Siponimod comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take siponimod 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 siponimod exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them.

Your doctor will probably start you on a low dose of siponimod and gradually increase your dose for the first 5 or 6 days.

Siponimod may cause the 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 siponimod 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 or take certain medications 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 also 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.

Siponimod may help control multiple sclerosis but will not cure it. Do not stop taking siponimod without talking to your doctor.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with siponimod 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 (https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) 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 siponimod,

• tell your doctor and pharmacist if you are allergic to siponimod any other medications, or any of the ingredients in siponimod tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take while taking siponimod. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• Certain genetic changes may cause some patients to respond differently to siponimod. Your doctor will order blood work to check your genetic make-up before you start siponimod. Based on the results, they may decide you can't take siponimod or they may have to change the dose for you.
• tell your doctor if you have or have had any of these conditions in the last six months: heart attack, angina (chest pain), stroke or mini-stroke, or heart failure. Also tell your doctor if you have an irregular heart rhythm. Your doctor may tell you not to take siponimod.
• tell your doctor if you have ever fainted, had a heart attack, stroke, or mini stroke; if you currently have a fever or other signs of infection or 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) or other eye problems; a slow heartbeat; skin cancer, or heart or liver disease. Also tell your doctor if you have recently received a vaccine.
• tell your doctor if you are pregnant or plan to become pregnant, or are breastfeeding. You should use birth control to prevent pregnancy during your treatment and for at least 10 days after your final dose. If you become pregnant while taking siponimod or within 10 days after your final dose, call your doctor.
• do not have any vaccinations for 1 week before you begin your treatment with siponimod, during your treatment, or for 1 month after your final dose without talking to your doctor. Talk to your doctor about vaccinations that you may need to receive before beginning your treatment with siponimod.
• 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 1 month before beginning your treatment with siponimod.
• plan to avoid unnecessary or prolonged exposure to sunlight and UV light (such as tanning booths) and to wear protective clothing, sunglasses, and sunscreen. Siponimod may make your skin more sensitive to the dangerous side effects of sunlight, and may increase your risk of developing skin cancer.

Unless your doctor tells you otherwise, continue your normal diet.

If you miss 1 or more doses of siponimod during the initial titration period, call your doctor as you will need to restart treatment. If you have certain heart conditions, you may need to be monitored by your doctor for at least 6 hours when you take your next dose.

If you miss 1 to 3 days of siponimod after the titration period (maintenance dose), take the missed tablet as soon as you remember and continue your treatment. If you miss taking 4 or more days in a row of siponimod after the titration period (maintenance dose), call your doctor as you will need to restart treatment. If you have certain heart conditions, you may need to be monitored by your doctor for at least 6 hours when you restart treatment.

Siponimod may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• pain in the arms, legs, hands, or feet
• diarrhea
• headache

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• slow heartbeat
• sore throat, body aches, fever, chills, cough, vomiting, and other signs of infection and during treatment and for up to 1 month after your treatment
• headache, neck stiffness, fever, sensitivity to light, nausea, or confusion during treatment and for up to 1 month after your treatment
• sudden severe headache, confusion, changes in vision, or seizures
• blurriness, shadows, or a blind spot in the center of your vision; sensitivity to light; unusual color to your vision or other vision problems
• weakness on one side of the body or clumsiness of the arms or legs that worsens over time; changes in your thinking, memory, or balance; confusion or personality changes; or loss of strength
• new or worsening shortness of breath
• nausea, vomiting, loss of appetite, abdominal pain, yellowing of skin or eyes, or dark urine
• swelling of the hands, ankles, or feet

Siponimod may increase the risk of developing skin cancer. Your doctor will check your skin before and during treatment for signs of skin cancer. If you experience any of the following symptoms, call your doctor immediately: new sores or discoloration on the skin; changes in mole shape, size, or color or bleeding; small lesion with an irregular border; or skin growths or bumps that appear shiny, pearly white, skin-colored, or pink. Talk to your doctor about the risks of taking this medication.

A sudden increase episodes of MS symptoms and worsening of disability may occur after you stop taking siponimod. Tell your doctor if your MS symptoms worsen after stopping siponimod.

Siponimod 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 (https://www.fda.gov/Safety/MedWatch) 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 unopened containers of this medication in the refrigerator. Opened blister packs and bottles may be stored at room temperature and away from excess heat and moisture (not in the bathroom) for 3 months. Do not refrigerate the tablets after opening.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. https://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (https://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include the following:

• slowed or irregular heartbeat

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests, 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 siponimod.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking siponimod.

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.

• Mayzent^®