• Ponvory is a prescription medicine that is used to treat relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease, in adults.
• It is not known if this medicine is safe and effective in children.

Ponvory may cause serious side effects, including:

1. Infections. Ponvory can increase your risk of serious infections that can be life-threatening and cause death. Ponvory lowers the number of white blood cells (lymphocytes) in your blood. This will usually go back to normal within 1 to 2 weeks of stopping treatment. Your healthcare provider should review a recent blood test of your white blood cells before you start treatment.

Call your healthcare provider right away if you have any of these symptoms of an infection during treatment with Ponvory and for 1 to 2 weeks after your last dose:

• • fever
  • vomiting
  • tiredness
  • headache with fever, neck stiffness, sensitivity to light, nausea, or confusion (these may be symptoms of meningitis, an infection of the lining around your brain and spine)
  • body aches
  • chills
  • nausea
    Your healthcare provider may delay starting or may stop your treatment if you have an infection.

2. Slow heart rate (bradycardia or bradyarrhythmia) when you start taking Ponvory. Ponvory can cause your heart rate to slow down, especially after you take your first dose. You should have a test to check the electrical activity of your heart called an electrocardiogram (ECG) before you take your first dose. Only start your treatment using the Starter Pack. You must use the Starter Pack to slowly increase the dose over a 14-day period to help reduce the effect of slowing of your heart rate. It is important to follow the recommended dosing instructions. See How should I take Ponvory?

Call your healthcare provider if you experience the following symptoms of slow heart rate:

• • dizziness
  • shortness of breath
  • lightheadedness
  • confusion
  • feeling like your heart is beating slowly or skipping beats
  • chest pain
  • tiredness
    Follow directions from your healthcare provider when starting treatment and when you miss a dose. See How should I take Ponvory?
    See Ponvory side effects for more information about side effects.

You will receive a 14-day starter pack. You must start Ponvory by slowly increasing doses over the first two weeks. Follow the dose schedule in the table below. This may reduce the risk of slowing of the heart rate.

• Take Ponvory exactly as your healthcare provider tells you to take it.
• Take Ponvory 1 time each day.
• Swallow the Ponvory tablets whole.
• Take the tablets with or without food.
• Do not stop taking Ponvory without talking with your healthcare provider first.
• Do not skip a dose.
• Start taking Ponvory with a 14-day starter pack.
• If you miss taking 1, 2, or 3 tablets in a row of Ponvory in the 14-day starter pack, continue treatment by taking the first dose you missed. Take 1 tablet as soon as you remember. Then, take 1 tablet a day to continue with the starter pack dose as planned.
• If you miss taking 1, 2, or 3 tablets in a row of Ponvory while taking the 20 mg maintenance dose, continue treatment with the 20 mg maintenance dose.
• If you miss taking 4 or more tablets in a row of Ponvory, while taking the 14-day starter pack or the 20 mg maintenance dose, you need to restart treatment with a new 14-day starter pack. Call your healthcare provider if you miss 4 or more doses of Ponvory. Do not restart Ponvory after stopping it for 4 or more days in a row without talking to your healthcare provider. If you have certain heart conditions, you may need to be monitored by your healthcare provider for at least 4 hours when you take your next dose.
• Write down the date you start taking Ponvory so you will know if you miss 4 or more doses in a row.

Do not take Ponvory if you:

• have had a heart attack, chest pain called 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 heart block or irregular or abnormal heartbeat (arrhythmia), unless you have a pacemaker.
  Talk to your healthcare provider before taking Ponvory if you have any of these conditions, or do not know if you have any of these conditions.

Before you take Ponvory

Before you start treatment, tell your healthcare provider about all of your medical conditions, including if you:

• have a fever or infection, or you are unable to fight infections due to a disease or taking medicines that weaken your immune system.
• have had chicken pox or have received the vaccine for chicken pox. Your healthcare provider may do a blood test for chicken pox virus. You may need to get the full course of vaccine for chicken pox and then wait 1 month before you start taking Ponvory.
• have slow heart rate.
• have an irregular or abnormal heartbeat (arrhythmia).
• have a history of stroke.
• have heart problems, including a heart attack or chest pain.
• have breathing problems, including during your sleep (sleep apnea).
• have liver problems.
• have high blood pressure.
• had or now have a type of skin cancer called basal cell carcinoma (BCC), melanoma, or squamous cell carcinoma.
• have eye problems, especially an inflammation of the eye called uveitis.
• have diabetes.
• are pregnant or plan to become pregnant. Ponvory may harm your unborn baby. Talk with your healthcare provider if you are pregnant or plan to become pregnant. If you are a woman who can become pregnant, you should use effective birth control during your treatment, and for 1 week after you stop taking Ponvory. Talk to your healthcare provider about what method of birth control is right for you during this time.
  Tell your healthcare provider right away if you do become pregnant during treatment or within 1 week after you stop taking Ponvory.
• are breastfeeding or plan to breastfeed. It is not known if Ponvory passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Ponvory.

Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. Using Ponvory and other medicines together may affect each other causing serious side effects. Especially tell your healthcare provider if you take or have taken:

• medicines to control your heart rhythm (antiarrhythmics), or blood pressure (antihypertensives), or heart beat (such as calcium channel blockers or beta-blockers).
• medicines that affect your immune system, such as alemtuzumab.
• medicines such as rifampin, phenytoin, or carbamazepine.
• You should not receive live vaccines during treatment, for at least 1 month before, and for 1 to 2 weeks after you stop treatment. If you receive a live vaccine, you may get the infection the vaccine was meant to prevent. Vaccines may not work as well when given during treatment with Ponvory.

Talk with your healthcare provider if you are not sure if you take any of these medicines. Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist when you get a new medicine.

Ponvory may cause serious side effects, including:

• See Important information
• breathing problems. Some people who take Ponvory have shortness of breath. Call your healthcare provider right away if you have new or worsening breathing problems.
• liver problems. Ponvory may cause liver problems. Your healthcare provider should do blood tests to check your liver before you start treatment. Call your healthcare provider right away if you have any of the following symptoms of liver problems:
  • unexplained nausea
  • loss of appetite
  • vomiting
  • yellowing of the whites of your eyes or skin
  • stomach (abdominal) pain o dark urine
  • tiredness
• increased blood pressure. Your healthcare provider should check your blood pressure during treatment.
• types of skin cancer called basal cell carcinoma (BCC), melanoma, and squamous cell carcinoma. Certain types of skin cancer have happened with drugs in the same class. Tell your healthcare provider if you have any changes in the appearance of your skin, including changes in a mole, a new darkened area on your skin, a sore that does not heal, or growths on your skin, such as a bump that may be shiny, pearly white, skin-colored, or pink. Your doctor should check your skin for any changes during treatment. Limit the amount of time you spend in sunlight and ultraviolet (UV) light. Wear protective clothing and use a sunscreen with a high sun protection factor.
• a problem with your vision called macular edema. Tell your healthcare provider about any changes in your vision. Your healthcare provider should test your vision before you start treatment and any time you notice vision changes during treatment with Ponvory. Your risk of macular edema is higher if you have diabetes or have had an inflammation of your eye called uveitis.
  Call your healthcare provider right away if you have any of the following symptoms:
  • blurriness or shadows in the center of your vision
  • sensitivity to light
  • a blind spot in the center of your vision
  • unusually colored (tinted) vision
• swelling and narrowing of  the blood vessels in your brain. A condition called Posterior Reversible Encephalopathy Syndrome (PRES) has happened with drugs in the same class. Symptoms of PRES usually get better when you stop taking Ponvory. However, if left untreated, it may lead to a stroke. Call your healthcare provider right away if you have any of the following symptoms:
  • sudden severe headache
  • sudden loss of vision or other changes in your vision
  • sudden confusion
  • seizure
• severe worsening of multiple sclerosis (MS) after stopping Ponvory. When Ponvory is stopped, symptoms of MS may return and become worse compared to before or during treatment. Always talk to your healthcare provider before you stop taking Ponvory for any reason. Tell your healthcare provider if you have worsening symptoms of MS after stopping Ponvory.

The most common side effects include:

• upper respiratory tract infections
• elevated liver enzymes (abnormal liver tests)
• high blood pressure

These are not all of the possible side effects. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088.

Ponvorycan cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Tell your doctor about all your other medicines, especially:

• alemtuzumab;

• rifampin;

• heart or blood pressure medication;

• seizure medicine such as carbamazepine or phenytoin; or other drugs that weaken the immune system (cancer medicine, steroids, medicines to prevent organ transplant rejection).

• This list is not complete. Other drugs may affect ponesimod, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Ponvorycan have long lasting effects on your body, especially on your immune system. For 1 or 2 weeks after your last dose, tell any doctor who treats you that you have used Ponvory.