Ponesimod

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 other reasons not mentioned in this medication guide.

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.

Ponesimod can slow your heart rate when you begin using it. Inform your doctor if you experience slow heartbeats, chest pain, shortness of breath, or a sensation of your heart skipping beats.

You may become more susceptible to infections, including serious or life-threatening infections. Contact your doctor if you have a fever, chills, aches, fatigue, vomiting, neck stiffness, confusion, or increased sensitivity to light. Your risk of infection may continue for 2 weeks after you stop taking ponesimod.

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.

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

Ponesimod may cause serious side effects. Call your doctor right away if you have:

• slow heartbeats, chest pain, shortness of breath, or feel like your heart is skipping beats;
• a light-headed feeling, as if you might faint;
• 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, body 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.

Usual Adult Dose for Multiple Sclerosis:

Treatment Initiation:2 mg orally once a day on Day 1 and 23 mg orally once a day on Day 3 and 44 mg orally once a day on Day 5 and 65 mg orally once a day on Day 76 mg orally once a day on Day 87 mg orally once a day on Day 98 mg orally once a day on Day 10 9 mg orally once a day on Day 1110 mg orally once a day on Days 12, 13, and 14Maintenance Dose:20 mg orally once a day starting on Day 15Use: For the treatment of adult patients with relapsing forms of multiple sclerosis (MS), toinclude clinically isolated syndrome, relapsing-remitting disease, and active secondaryprogressive diseaseComments:-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).

If you miss up to 3 doses from the Ponvory Starter Pack 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 take 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.

Do not get 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, and varicella (chickenpox).

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.

Ponesimod can lead to a serious heart issue. Your risk might be higher if you also take certain other medications for infections, asthma, heart issues, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Inform your doctor about all your other medications, especially:

• alemtuzumab;
• rifampin;
• heart or blood pressure medication;
• seizure medications like carbamazepine or phenytoin; or other drugs that weaken the immune system (cancer medications, steroids, medications to prevent organ transplant rejection).
• This list is not complete. Other drugs may impact ponesimod, including prescription and over-the-counter medications, vitamins, and herbal products. Not all possible drug interactions are listed here.

Ponesimod can have long-term effects on your body, particularly on your immune system. For 1 or 2 weeks after your last dose, inform any doctor who treats you that you have used ponesimod.