PONVORY 2, 3, 4, 5, 6, 7, 8, 9 and 10 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Ponvory 2 mg film-coated tablets

Ponvory 3 mg film-coated tablets

Ponvory 4 mg film-coated tablets

Ponvory 5 mg film-coated tablets

Ponvory 6 mg film-coated tablets

Ponvory 7 mg film-coated tablets

Ponvory 8 mg film-coated tablets

Ponvory 9 mg film-coated tablets

Ponvory 10 mg film-coated tablets

Ponvory 20 mg film-coated tablets

ponesimod

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Ponvory and what is it used for
2. What you need to know before you take Ponvory
3. How to take Ponvory
4. Possible side effects
5. Storage of Ponvory
6. Contents of the pack and other information

1. What is Ponvory and what is it used for

What is Ponvory

Ponvory contains the active substance ponesimod. Ponesimod belongs to a group of medicines called sphingosine-1-phosphate receptor modulators (S1P).

What is Ponvory used for

Ponvory is used to treat adults with relapsing forms of multiple sclerosis (RMS) with active disease. Active disease in RMS is when there are relapses or when MRI (magnetic resonance imaging) scan results show signs of inflammation.

What is multiple sclerosis?

Multiple sclerosis (MS) affects the nerves in the brain and spinal cord (the central nervous system).

In MS, the immune system (one of the body's main defense systems) does not work properly. The immune system attacks a protective covering of nerve cells called the myelin sheath, causing inflammation. This breakdown of the myelin sheath (called demyelination) stops the nerves from working properly.

The symptoms of MS depend on which parts of the brain and spinal cord are affected. They can include problems with walking and balance, weakness, numbness, double vision and blurred vision, poor coordination, and bladder problems.

Symptoms of a relapse may disappear completely when the relapse is over, but some problems may persist.

How Ponvory works

Ponvory reduces the number of circulating lymphocytes, which are white blood cells involved in the immune system. It does this by keeping them in lymphoid organs (lymph nodes). This means there are fewer lymphocytes available to attack the myelin sheath surrounding the nerves in the brain and spinal cord.

By reducing the damage to nerves in MS patients, it reduces the number of relapses, and slows down the worsening of the disease.

2. What you need to know before you take Ponvory

Do not take Ponvory if

• you are allergic to ponesimod or any of the other ingredients of this medicine (listed in section 6)
• your healthcare professional has told you that you have a severely weakened immune system
• you have had a heart attack, unstable angina (chest pain), stroke, or transient ischaemic attack (TIA, a "mini-stroke") or certain types of heart failure in the last 6 months
• you have certain types of heart block (abnormal heart tracing on an ECG) or irregular or abnormal heartbeats (arrhythmia), unless you have a pacemaker
• you have a severe active infection or an active chronic infection
• you have active cancer
• you have moderate or severe liver problems
• you are pregnant or are a woman of childbearing potential who is not using an effective method of contraception

If you are not sure if you have any of these conditions, consult your doctor before taking Ponvory.

Warnings and precautions

Talk to your doctor before taking Ponvory if:

• you have irregular, abnormal, or slow heartbeats
• you have ever had a stroke or other conditions related to the blood vessels in the brain
• you have ever fainted or passed out suddenly (syncope)
• you have a fever or an infection
• you have an immune system that does not work properly due to a disease or because you are taking medicines that weaken your immune system
• you have never had chickenpox or have not received a chickenpox vaccine. Your doctor may do a blood test to check for the chickenpox virus. You may need to undergo a full course of chickenpox vaccination and then wait 1 month before starting Ponvory
• you have respiratory problems (such as severe respiratory disease, pulmonary fibrosis, or chronic obstructive pulmonary disease)
• you have liver problems
• you have diabetes. The risk of developing macular edema (see below) is higher in patients with diabetes
• you have eye problems, especially an inflammation of the eye called uveitis
• you have high blood pressure.

If you are in any of these situations (or are unsure), consult your doctor before taking Ponvory.

Tell your doctor immediatelyif you notice any of the following side effects while taking Ponvory:

Low heart rate (bradycardia or bradyarrhythmia)

Ponvory may lower your heart rate, especially after taking your first dose. An electrocardiogram (ECG, to check the electrical activity of your heart) should be done before taking your first dose of Ponvory, or before restarting Ponvory after a treatment interruption.

• If you are at high risk of side effects due to a decrease in your heart rate, your doctor may monitor your heart rate and blood pressure for at least 4 hours after giving you your first dose of Ponvory.
• You will also have an ECG at the end of the 4 hours. If you still have a very low or decreasing heart rate, monitoring may need to be continued until it resolves.

Infections

Ponvory may increase your risk of serious infections that can be life-threatening. Ponvory reduces the number of lymphocytes in your blood. These cells fight infections. Usually, the number of these cells will return to normal during the week after treatment is stopped. Your doctor should check your blood cell count in a recent blood test before starting Ponvory.

Tell your doctor immediately if you have any of these symptoms of an infection during treatment with Ponvory or during the week after your last dose of Ponvory:

• fever
• fatigue
• body aches
• chills
• nausea
• vomiting
• headache with fever, stiff neck, sensitivity to light, nausea, confusion (these can be symptoms of meningitis, an infection of the layer covering your brain and spinal cord).

Macular edema

Ponvory may cause a problem with your vision called macular edema (a buildup of fluid in the back of the eye (retina) that can cause changes in vision, including blindness).

Symptoms of macular edema may be similar to visual symptoms of an MS relapse (called optic neuritis). At first, there may be no symptoms. Make sure to tell your doctor about any changes in your vision. If macular edema occurs, it usually starts in the first 6 months after starting Ponvory.

Your doctor should check your vision before starting Ponvory and also whenever you notice changes in your vision during treatment. Your risk of macular edema is higher if you have diabetes or if you have had an eye inflammation called uveitis.

Tell your doctor immediately if you notice any of the following:

• blurred vision or shadows in the center of your field of vision
• a blind spot in the center of your field of vision
• sensitivity to light
• unusually colored vision (tinged).

Liver problems

Ponvory may cause liver problems. Your doctor should do blood tests to check your liver function before starting Ponvory.

Tell your doctor immediately if you notice any of the following symptoms of liver problems:

• nausea
• vomiting
• stomach pain
• fatigue
• loss of appetite
• your skin or the whites of your eyes turn yellow
• dark urine.

Increased blood pressure

Since Ponvory may increase your blood pressure, your doctor should check it regularly during treatment with Ponvory.

Sun exposure and sun protection

Since Ponvory may increase your risk of skin cancer, you should limit your exposure to sunlight and ultraviolet (UV) light:

• by wearing protective clothing
• by applying sunscreen regularly with a high sun protection factor.

Breathing problems

Some people taking Ponvory have difficulty breathing. Tell your doctor immediately if you have new or worsening breathing problems.

Swelling and narrowing of the blood vessels in your brain

The use of medicines that work in a similar way to Ponvory has caused a condition called posterior reversible encephalopathy syndrome (PRES). Symptoms of PRES usually improve when you stop taking Ponvory. However, if left untreated, it can cause a stroke.

Tell your doctor immediately if you notice any of the following symptoms:

• sudden severe headache
• sudden confusion
• sudden loss of vision or other changes in vision
• seizures.

Worsening of multiple sclerosis after stopping Ponvory

When treatment with Ponvory is stopped, MS symptoms may return. They may worsen compared to the situation before or during treatment. Always talk to your doctor before stopping Ponvory. Tell your doctor if your MS symptoms worsen after stopping Ponvory.

Children and adolescents

Ponvory has not been studied in children and adolescents, so it is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Ponvory

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription, vitamins, and herbal supplements. Tell your doctor especially if you are taking:

• medicines to control your heart rate (anti-arrhythmics), blood pressure (anti-hypertensives), or heartbeats (such as calcium channel blockers or beta-blockers that can lower your heart rate).
• medicines that affect your immune system, due to a possible additive effect on the immune system.

Vaccines and Ponvory

Tell your doctor if you have recently received a vaccine or if you are scheduled to receive a vaccine. You should avoid receiving live vaccines during treatment with Ponvory. If you receive a live vaccine, you may catch the infection that the vaccine is meant to prevent. Treatment with Ponvory should be stopped 1 week before and during 4 weeks after receiving a live vaccine.

Also, other vaccines may not work if given during treatment with Ponvory.

Pregnancy, contraception, and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

• Do not take Ponvory during pregnancy. If Ponvory is used during pregnancy, it may harm the fetus.
• Do not take it if you are trying to get pregnant or if you are a woman of childbearing potential and not using an effective method of contraception.

Women of childbearing potential/contraception in women

If you are a woman of childbearing potential:

• Your doctor will inform you about the risk of harming the fetus before starting treatment with Ponvory, and a pregnancy test should be done to check that you are not pregnant.
• You must use an effective method of contraception while taking Ponvory and also for 1 week after stopping it.

Talk to your doctor about reliable methods of contraception.

If you become pregnant while taking Ponvory, stop taking Ponvory and tell your doctor immediately.

If you become pregnant during the week after stopping Ponvory, talk to your doctor.

Breastfeeding

Do not breastfeed while taking Ponvory. This is to avoid the risk of side effects for the baby, as Ponvory may pass into breast milk.

Driving and using machines

Ponvory is not expected to affect your ability to drive and use machines.

Ponvory contains lactose

Ponvory contains lactose, which is a type of sugar. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Ponvory contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Ponvory

Follow the instructions for taking this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

How to take it

• Take Ponvory exactly as your doctor has told you. Do not change your dose or stop taking Ponvory unless your doctor tells you to.
• Take only 1 tablet a day. To help you remember to take your medicine, take it at the same time every day.
• Take it with or without food.

Treatment initiation pack (14 days)

• Onlystart your treatment with Ponvory using the treatment initiation pack, with which the dose will be gradually increased over 14 days. The purpose of the dose titration phase is to reduce any side effects due to a decrease in heart rate at the start of treatment.
• Write the date you start taking the medicine next to Day 1 on the Ponvory treatment initiation pack.
• Follow this 14-day treatment schedule.

Maintenance dose

• Afterfinishing the tablets in the treatment initiation pack, continue treatment with the maintenance dose of 20 mg.
• Write the date you start taking the 20 mg maintenance dose next to Week 1 on the Ponvory 20 mg blister pack.

If you take more Ponvory than you should

If you have taken more Ponvory than you should, tell your doctor immediately or go immediately to a hospital. Take the medicine pack and this leaflet with you.

If you forget to take Ponvory

Do not take a double dose to make up for forgotten doses.

• If you forget to take up to 3 Ponvory tablets in a row while taking the treatment initiation pack or the maintenance dose, you can continue treatment by taking the first missed dose. Take 1 tablet as soon as you remember, then take 1 tablet a day to continue with the treatment initiation pack dose or the maintenance dose as planned.
• If you forget to take 4 or more Ponvory tablets in a row while taking the treatment initiation pack or the maintenance dose, you must restart treatment with a new 14-day treatment initiation pack. Tell your doctor immediately if you forget 4 or more Ponvory doses.

Write the date you start taking the medicine to know if you miss 4 or more doses in a row.

Do not stop taking Ponvory without talking to your doctor first.

Do not restart treatment with Ponvory after stopping it for 4 or more days in a row without consulting your doctor. You will need to restart your treatment with a new treatment initiation pack.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Some adverse effects can be or may become severe

Immediately inform your doctor or pharmacist if you observe any of the adverse effects listed below, because they may be signs of severe effects:

Frequent(may affect up to 1 in 10 people)

• urinary tract infection
• bronchitis
• flu (influenza)
• viral infection of the nose, throat, or chest (viral respiratory tract infection)
• viral infection
• herpes zoster virus infection (shingles)
• pneumonia (lung infection)
• feeling of dizziness (vertigo)
• fever (pyrexia)
• fluid accumulation in the back of the eye (retina) that can cause vision changes, including blindness (macular edema)
• seizures (convulsions)

Infrequent(may affect up to 1 in 100 people)

• slow heart rate (bradycardia)

Other adverse effects

Very Frequent(may affect more than 1 in 10 people)

• nose, sinus, or throat infection (nasopharyngitis, respiratory tract infection)
• increased liver enzyme levels in blood (a sign of liver problems)
• low number of a type of white blood cell called lymphocytes (lymphopenia)

Frequent(may affect up to 1 in 10 people)

• high blood pressure (hypertension)
• back pain
• feeling very tired (fatigue)
• feeling dizzy
• difficulty breathing (dyspnea)
• high cholesterol levels in blood (hypercholesterolemia)
• joint pain (arthralgia)
• pain in arms or legs
• depression
• difficulty sleeping (insomnia)
• cough
• itching, secretion, or nasal congestion (rhinitis), infected or irritated throat (pharyngitis, laryngitis), or sinus infection (sinusitis)
• feeling anxious (anxiety)
• decreased sensation or sensitivity, especially in the skin (hypoesthesia)
• increased level of a protein in the blood that may indicate infection or inflammation (increased C-reactive protein level)
• drowsiness (somnolence)
• indigestion (dyspepsia)
• swollen hands, ankles, or feet (peripheral edema)
• migraine
• ligament sprain
• chest discomfort

Infrequent(may affect up to 1 in 100 people)

• high potassium levels in blood (hyperkalemia)
• swollen joint
• dry mouth

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Ponvory

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the box and blister pack after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Ponvory Composition

• The active ingredient is ponesimod.

• The other excipients are:

Core of the tablet

Sodium croscarmellose, lactose monohydrate (see "Ponvory contains lactose"), magnesium stearate, microcrystalline cellulose, Povidone K30, anhydrous colloidal silica, and sodium lauryl sulfate.

Tablet coating

Hypromellose 2910, lactose monohydrate, Macrogol 3350, titanium dioxide, and triacetin.

Ponvory 3 mg film-coated tablets

Red iron oxide (E172) and yellow iron oxide (E172)

Ponvory 4 mg film-coated tablets

Red iron oxide (E172) and black iron oxide (E172)

Ponvory 5 mg film-coated tablets

Black iron oxide (E172) and yellow iron oxide (E172)

Ponvory 7 mg film-coated tablets

Red iron oxide (E172) and yellow iron oxide (E172)

Ponvory 8 mg film-coated tablets

Red iron oxide (E172) and black iron oxide (E172)

Ponvory 9 mg film-coated tablets

Red iron oxide (E172), black iron oxide (E172), and yellow iron oxide (E172)

Ponvory 10 mg film-coated tablets

Red iron oxide (E172) and yellow iron oxide (E172)

Ponvory 20 mg film-coated tablets

Yellow iron oxide (E172)

Product Appearance and Package Contents

Ponvory 2 mg film-coated tablets are white, round, biconvex, film-coated tablets with a diameter of 5 mm, with "2" on one side and an arc on the other side.

Ponvory 3 mg film-coated tablets are red, round, biconvex, film-coated tablets with a diameter of 5 mm, with "3" on one side and an arc on the other side.

Ponvory 4 mg film-coated tablets are purple, round, biconvex, film-coated tablets with a diameter of 5 mm, with "4" on one side and an arc on the other side.

Ponvory 5 mg film-coated tablets are green, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "5" on one side and an arc and "A" on the other side.

Ponvory 6 mg film-coated tablets are white, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "6" on one side and an arc and "A" on the other side.

Ponvory 7 mg film-coated tablets are red, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "7" on one side and an arc and "A" on the other side.

Ponvory 8 mg film-coated tablets are purple, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "8" on one side and an arc and "A" on the other side.

Ponvory 9 mg film-coated tablets are brown, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "9" on one side and an arc and "A" on the other side.

Ponvory 10 mg film-coated tablets are orange, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "10" on one side and an arc and "A" on the other side.

Ponvory 20 mg film-coated tablets are yellow, round, biconvex, film-coated tablets with a diameter of 8.6 mm, with "20" on one side and an arc and "A" on the other side.

Initial Treatment Package of Ponvory (Box Configuration)

Each blister pack of 14 film-coated tablets for a 2-week treatment regimen contains:

2 film-coated tablets of 2 mg

2 film-coated tablets of 3 mg

2 film-coated tablets of 4 mg

1 film-coated tablet of 5 mg

1 film-coated tablet of 6 mg

1 film-coated tablet of 7 mg

1 film-coated tablet of 8 mg

1 film-coated tablet of 9 mg

3 film-coated tablets of 10 mg

Ponvory 20 mg film-coated tablets (Maintenance Package) (Box Configuration)

Package with 28 film-coated tablets for a 4-week treatment regimen or multiple package with 84 (3 packages of 28) film-coated tablets for a 12-week treatment regimen.

Only some package sizes may be marketed.

Marketing Authorization Holder

LABORATOIRES JUVISE PHARMACEUTICALS

149 Boulevard Bataille de Stalingrad

69100 Villeurbanne

France

Manufacturer

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu