Ponesimod is used to treat relapsing forms of multiple sclerosis in adults (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease).

Ponesimod may also be used for purposes not listed in this medication guide.

Ponesimod can slow your heart rate when you start taking it. Tell your doctor if you have slow heartbeats, chest pain, shortness of breath, or feel like your heart is skipping beats.

You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, chills, aches, tiredness, vomiting, neck stiffness, confusion, increased sensitivity to light. Your risk of infection could last for 2 weeks after you stop taking ponesimod.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Ponesimod can slow your heart rate when you start taking it. Before your first dose, your heart function will be checked using an electrocardiograph or ECG (sometimes called an EKG).

Ponesimod comes in a 14-day starter pack containing tablets of different colors and strengths. Taking the tablets in order will increase your dose gradually during the first 2 weeks.

You may take ponesimod with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

You may get infections more easily, even serious or fatal infections. You will need frequent medical tests, and your risk of infection could last for 2 weeks after you stop taking ponesimod.

If you get an infection, further doses may be delayed until your infection clears up. If you stop taking ponesimod, you may need to use a starter pack again, to gradually increase your dose.

Store at room temperature away from moisture and heat.

Always ask your doctor before you stop taking ponesimod for any reason. Your MS symptoms may return and become worse than before or during treatment with this medicine. Tell your doctor if you have any signs of worsening MS.

Usual Adult Dose for Multiple Sclerosis:

Treatment Initiation:
2 mg orally once a day on Day 1 and 2
3 mg orally once a day on Day 3 and 4
4 mg orally once a day on Day 5 and 6
5 mg orally once a day on Day 7
6 mg orally once a day on Day 8
7 mg orally once a day on Day 9
8 mg orally once a day on Day 10
9 mg orally once a day on Day 11
10 mg orally once a day on Days 12, 13, and 14

Maintenance Dose:
20 mg orally once a day starting on Day 15

Use: For the treatment of adult patients with relapsing forms of multiple sclerosis (MS), to
include clinically isolated syndrome, relapsing-remitting disease, and active secondary
progressive disease

Comments:
-Starter pack must be used for patients initiating treatment (14-day titration pack).
-Patients undergoing therapy initiation may develop a decrease in heart rate.
-Administer the first dose in a setting where resources to properly manage symptomatic bradycardia are available.
-First-dose 4-hour monitoring is recommended for patients with sinus bradycardia [HR less than 55 beats per minute (bpm)], first- or second-degree (Mobitz type I) AV block, or a history of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in stable condition.
-Interruption during treatment, especially during titration, is not recommended.
-Prior to therapy, obtain and review appropriate laboratory tests and medical examinations.
-Establish if patients are taking drugs that could slow heart rate or atrioventricular conduction before starting treatment.
-Consider possible unintended additive immunosuppressive effects before initiating treatment in patients taking or with prior use of anti-neoplastic, immunosuppressive, or immune-modulating therapies.
-Initiating this drug after treatment with alemtuzumab is not recommended.
-Assess vaccination status and test for antibodies to varicella zoster virus (VZV).

You should not use ponesimod if you are allergic to it, or if you have certain serious heart conditions, especially:

• "AV block" or sick sinus syndrome (unless you have a pacemaker); or

• recent (within the past 6 months) heart failure, heart attack, stroke, "mini-stroke" or TIA, chest pain (unstable angina), or other serious heart problem.

Some heart rhythm medications can cause unwanted or dangerous effects when used with ponesimod. Your doctor may change your treatment plan if you also use amiodarone, disopyramide, dofetilide, dronedarone, ibutilide, procainamide, quinidine, or sotalol.

Before you take ponesimod, tell your doctor if you have never had chickenpox or received a varicella vaccine (Varivax). You may need to receive the vaccine and then wait 1 month before taking ponesimod.

Tell your doctor if you have received any vaccine within the past 30 days, or if you are scheduled to receive a vaccine.

Tell your doctor if you have a fever or infection, or if you have ever had:

• a weak immune system (caused by disease or by using certain medicine);

• a very slow heart rate;

• heart rhythm problems, long QT syndrome;

• a heart attack, stroke, or chest pain;

• high blood pressure;

• sleep apnea or other breathing problems;

• diabetes;

• liver disease;

• an eye condition called uveitis; or

• skin cancer including melanoma, or basal or squamous cell carcinoma.

May harm an unborn baby. Use effective birth control while using ponesimod and for at least 1 week after your last dose. Tell your doctor if you become pregnant.

Ask a doctor if it is safe to breastfeed while using this medicine.

If you miss up to 3 starter pack doses in a row: Take 1 tablet as soon as you can, then take 1 tablet daily in the planned order for the rest of the pack.

If you miss a dose after the first 2 weeks: Skip the missed dose and use your next dose at the regular time.

Do not take two doses at one time.

Call your doctor if you miss 4 or more doses in a row. You will need to start over, and your heart function may need to be checked again.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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). If your medication came with a desiccant packet (small packet that contains a substance that absorbs moisture to keep the medication dry), leave the packet in the bottle but be careful not to swallow it.

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. http://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 (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

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

Avoid getting a vaccine without first asking your doctor. While you are taking ponesimod, a "live" vaccine may not fully protect you from disease and you could develop an infection.

Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

You should not receive a live vaccine within 1 month before taking ponesimod, while taking it, and for at least 1 to 2 weeks after you stop taking it.

You may have a higher risk of skin cancer while using ponesimod. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Ponesimod may cause serious side effects. Call your doctor at once if you have:

• slow heartbeats, chest pain, shortness of breath, or feel like your heart is skipping beats;

• a light-headed feeling, like you might pass out;

• sudden confusion, severe headache, vision loss, or a seizure;

• changes in vision--blurred vision, increased sensitivity to light, seeing an unusual color in your vision, or having a blind spot or shadows in the center of your vision;

• liver problems--nausea, vomiting, upper stomach pain, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes);

• skin changes--darkening, a new sore that does not heal, a change in the size or color of a mole, a growth or bump that looks shiny, pearly, or pink; or

• symptoms of infection--fever, headache, aches, tiredness, vomiting, neck stiffness, increased sensitivity to light.

Common side effects of ponesimod may include:

• cold symptoms such as stuffy nose, sneezing, sore throat;

• high blood pressure; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ponesimod can 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.

Ponesimod can 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 ponesimod.

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 ponesimod.

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.