Ponesimod belongs to the class of medications called sphingosine 1-phosphate (S1P) receptor modulators. It is used to treat the relapsing-remitting form of multiple sclerosis (MS).

Ponesimod does not cure MS, but it helps to reduce the number of attacks (relapses) that occur, reduce inflammation in the brain (brain lesions seen on MRI scans), and slow the buildup of physical problems due to progression of disability caused by MS.

Ponesimod works by lowering the number of white blood cells (lymphocytes) in your blood by preventing them from moving freely within the body. In MS, when lymphocytes reach the brain and spinal cord, they are thought to cause the inflammation that contributes to loss of the protective sheath (called myelin) that normally covers the nerve fibres and ensures that they work properly. Ponesimod may keep these cells from reaching the brain and spinal cord.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

The starting dose of ponesimod is 2 mg taken by mouth once daily. To reduce the effects of decreased heart rate and heart rhythm, the dose is gradually increased over 2 weeks. When you start this medication, you will be given an initiation package containing 14 tablets of different strengths of ponesimod. After 2 weeks of gradually increasing the dose, you will be able to switch over to the maintenance package. This contains the usual adult dose of ponesimod which is 20 mg taken by mouth once daily. Ponesimod may be taken with or without food.

Depending on other medical conditions you may have, your doctor may want you to remain in the clinic or office for as long as 4 hours, so your heart rate can be monitored.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss 1, 2, or 3 doses in a row, re-start the medication by taking the first dose that you missed. If you miss 4 or more doses in a row, you need to start over, with a new initiation pack, at 2 mg daily. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

2 mg
Each round, 5.0 mm, white, film-coated tablet debossed with "2" on one side and arch on the other side, contains 2 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, and triacetin.

3 mg
Each round, 5.0 mm, red, film-coated tablet debossed with "3" on one side and arch on the other side, contains 3 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide yellow.

4 mg
Each round, 5.0 mm, purple, film-coated tablet debossed with "4" on one side and arch on the other side, contains 4 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide black.

5 mg
Each round, 8.6 mm, green, film-coated tablet debossed with "5" on one side and "A" on the other side, contains 5 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide black, and iron oxide yellow.

6 mg
Each round, 8.6 mm, white. film-coated tablet debossed with "5" on one side and "A" on the other side, contains 6 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, and triacetin.

7 mg
Each round, 8.6 mm, red, film-coated tablet debossed with "7" on one side and "A" on the other side, contains 7 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide yellow.

8 mg
Each round, 8.6 mm, purple, film-coated tablet debossed with "8" on one side and "A" on the other side, contains 8 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide black.

9 mg
Each round, 8.6 mm, brown, film-coated tablet debossed with "9" on one side and "A" on the other side, contains 9 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, iron oxide black, and iron oxide yellow.

10 mg
Each round, 8.6 mm, orange, film-coated tablet debossed with "10" on one side and "A" on the other side, contains 10 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide yellow.

20 mg
Each round, 8.6 mm, yellow, film-coated tablet debossed with "20" on one side and "A" on the other side, contains 20 mg of ponesimod. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30, silica colloidal anhydrous, and sodium laurilsulfate; tablet coating (Opadry II): hydroxypropyl methylcellulose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, iron oxide red, and iron oxide yellow.

Do not take ponesimod if you:

• are allergic to ponesimod or any ingredients of the medication
• have a severe active infection or an active chronic infection such as hepatitis or tuberculosis
• have a weakened immune system due to disease (e.g., immunodeficiency syndrome) or are taking medicines or receiving treatments that suppress the immune system (e.g., to treat cancer or bone marrow transplantation)
• have an active cancer (except for a type of skin cancer called basal cell carcinoma)
• have moderate to severe liver disease
• have had a heart attack, unstable angina, a transient ischemic attack (mini-stroke), or heart failure in the past 6 months
• have heart block or sick-sinus syndrome and do not have a pacemaker
• are or may become pregnant and are not using effective birth control

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• anxiousness
• back pain
• breathlessness
• cold or flu virus infection with symptoms such as tiredness, chills, sore throat, joint or muscle aches, or fever
• cough
• dizziness
• dry mouth
• extreme tiredness
• fever
• heartburn
• itchy, runny, or stuffed nose
• joint or muscle pain
• ligament sprain
• migraine
• sinus infection
• spinning sensation
• swollen joints
• trouble sleeping

Although most of these side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• blurred vision, vision changes or sensitivity to light
• decreased sensitivity of the skin
• increased blood pressure
• irregular heartbeat (e.g., slow, fast, or pounding heartbeat; chest pain; dizziness; shortness of breath)
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• shortness of breath
• signs of liver problems (e.g., nausea, vomiting, loss of appetite, swelling and/or pain in the abdomen, fatigue, itching, yellowing of the skin or eyes, or dark urine)
• swollen hands, ankles, and feet
• symptoms of bronchitis such as cough with phlegm, chest pain, or fever
• symptoms of infection from herpes virus (shingles or herpes zoster) such as blisters, burning, itching, or pain around the mouth or genitals (other symptoms may include fever followed by numbness, itching, and red patches or blisters on the face or trunk, with severe pain)
• symptoms of a urinary tract infection (e.g. pain when urinating, urinating more often than usual, low back or flank pain)
• trouble breathing
• unusual growths on the skin (e.g., shiny, raised growths or purple, red, or brown blotches)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• seizures
• symptoms of meningitis (e.g., headache with stiff neck, sensitivity to light, nausea, confusion)
• symptoms of posterior reversible encephalopathy syndrome (PRES; e.g., include confusion, drowsiness, personality change, headache, paralysis, nausea, vomiting, vision changes)
• symptoms of progressive multifocal leukoencephalopathy (PML) (e.g., weakness on one side, problems thinking, vision changes)
• symptoms of progressive multifocal leukoencephalopathy (PML; e.g., weakness on one side of your body, problems thinking, vision changes)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Blood pressure: Ponesimod may increase blood pressure. Your doctor will monitor your blood pressure while you are taking this medication. If you have high blood pressure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Breathing disorders: Ponesimod may affect lung function for people with respiratory problems such as pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease. If you have respiratory problems, discuss with your doctor how this whether any special monitoring is needed.

Contact your doctor if you experience any new or worsening shortness of breath.

Cancer: Medications such as ponesimod may increase your risk for certain cancers, particularly skin cancer. Your doctor will monitor you for skin cancer while you are taking this medication. Report any changes to your skin, such as change in size, colour, or shape of moles, to your doctor as soon as possible. While you are taking ponesimod, it is important to limit your exposure to the sun and use appropriate sun protection such as sunscreen and protective clothing.

Depression: People with MS often experience depression more often than the general public. Ponesimod may contribute to the symptoms of depression. If you have depression or a history of depression, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of depression such as poor concentration, changes in weight, changes in sleep, decreased interest in activities, or notice them in a family member who is taking this medication, contact your doctor as soon as possible.

Eye problems: People who have diabetes or a history of inflammation of the middle of the eye are at an increased risk of developing swelling in the macula of the eye. It is recommended that you have an eye examination after taking this medication for 3 or 4 months to check for changes in your eyes that have not caused symptoms. Report any changes in vision, including blurred vision, light sensitivity, or blind spots to your doctor as soon as possible.

Heart problems: Ponesimod causes a decrease in heart rate shortly after taking the first dose. Your doctor will want to check your heart before you start this medication. If you have heart problems, you will need to be observed in a doctor's office or clinic for at least 4 hours after your first dose. This allows the doctor to monitor your heart rate and treat any problems before they become an emergency. It may be necessary to be monitored for a longer period of time if you develop very low heart rate or an irregular heartbeat.

If you have a heart problem, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart rhythm: This medication can cause changes to the normal rhythm of the heart, including an irregular heartbeat called QT prolongation. QT prolongation is a serious life-threatening condition that can cause fainting, seizures, and sudden death. If you are at risk for heart rhythm problems (e.g., people with heart failure, angina, low potassium or magnesium levels), discuss with your doctor whether any special monitoring is needed.

Infections: Ponesimod works by decreasing the number of white blood cells in the blood stream. White blood cells are responsible for fighting infection in the body. As a result, people taking ponesimod may have an increased risk of infections. If you notice signs of an infection, such as fever, redness, or swelling, contact your doctor as soon as possible.

Infections caused by varicella zoster (chicken pox, shingles) and herpes simplex viruses can cause life-threatening infections leading to inflammation of tissues of the brain (encephalitis, meningitis) or the failure of multiple organs in the body.

Liver function: Liver disease or reduced liver function may cause ponesimod to build up in the body, causing side effects. This medication may also reduce liver function and can cause liver failure. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Progressive multifocal leukoencephalopathy (PML): There have been reports of PML after using other similar medications and other medications used to treat MS. PML is a rare viral infection that causes nerve damage in the brain. If you experience memory loss, vision changes, trouble thinking, personality changes, or difficulty walking, contact your doctor immediately.

Posterior Reversible Encephalopathy Syndrome (PRES): This is a rare disease of the brain that may occur when using ponesimod. If you have had a previous episode of PRES, this may not be an appropriate medication for you. Make sure your doctor knows you have experienced this before. If you experience signs and symptoms of PRES, such as headache, nausea, vomiting, seizures, change in awareness or consciousness, or vision changes, contact your doctor immediately.

Seizures: If you have a history of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Ponesimod may increase the frequency of seizures.

Stopping this medication: Rarely, after this medication has been stopped, symptoms and flare-ups of MS return and may become worse than before starting ponesimod.

Vaccines: Some vaccines containing live viruses may result in the infection that the vaccination should prevent, when given while taking ponesimod. Other vaccines may not work well enough to protect you. Talk to your doctor about which vaccinations you need before starting treatment, and which vaccines to avoid during treatment.

Pregnancy: This medication may cause harm to an unborn fetus and should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately. If you are taking ponesimod and could become pregnant, you should use an effective method of birth control (e.g., birth control pill, condoms) during treatment, and for 2 weeks after stopping treatment with ponesimod.

Breast-feeding: It is not known if ponesimod passes into breast milk. If you are breast-feeding and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children and adolescents under the age of 18 years.

There may be an interaction between ponesimod and any of the following:

• antiarrhythmic medications (e.g., amiodarone, disopyramide, procainamide, quinidine, sotalol)
• anticancer medications (e.g., azacitidine, busulfan, capecitabine, cladribine, cytarabine, doxorubicin, etoposide, ifosfamide, methotrexate, mitoxantrone, vincristine)
• BCG
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• chlorpromazine
• clonidine
• corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
• cyclosporine
• denosumab
• digoxin
• diltiazem
• donepezil
• dronedarone
• echinacea
• galantamine
• haloperidol
• lacosamide
• lanreotide
• leflunomide
• medications that suppress or modulate the immune system, including medications used to treat MS (e.g., beta-interferon, glatiramer acetate, natalizumab)
• methadone
• midodrine
• mycophenolate
• octreotide
• other sphingosine 1-phosphate receptor modulators (e.g., fingolimod, ozanimod, siponimod)
• pasireotide
• pimecrolimus
• quinine
• rifampin
• rivastigmine
• romidepsin
• rosuvastatin
• seizure medications (e.g., carbamazepine, phenobarbital, phenytoin, primidone)
• sulfasalazine
• tacrolimus
• tizanidine
• tyrosine kinase inhibitors (e.g., baricitinib, bosutinib, ceritinib, dasatinib, nilotinib, sunitinib, tofacitinib)
• vaccines
• verapamil

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking.

Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.