Ponvory 20 mg film-coated tablets

Package leaflet: Information for the user

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

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Ponvory is and what it is used for

What Ponvory is

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

What Ponvory is 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) 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 defence 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 (known as demyelination) prevents nerves from functioning correctly.

The symptoms of MS depend on which parts of the brain and spinal cord are affected. They may 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 once the relapse has passed, but some problems may persist.

How Ponvory works

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

By reducing nerve damage in patients with MS, Ponvory decreases the number of relapses and delays the progression of disability.

2. What you need to know before taking 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 provider has told you that you have a severely weakened immune system
• you have had a heart attack, chest pain called unstable angina, stroke or mini-stroke (transient ischaemic attack, TIA), or certain types of heart failure within the past 6 months
• you have certain types of heart block (abnormal heart tracing on an ECG (electrocardiogram), usually with slow heartbeats) or irregular or abnormal heartbeats (arrhythmia), unless you have a pacemaker fitted
• you have an active serious 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 contraceptive method

If you are unsure whether you have any of these conditions, consult your doctor before starting Ponvory.

Warnings and precautions

Talk to your doctor before starting Ponvory if:

• you have irregular, abnormal or slow heartbeats
• you have ever had a stroke or other conditions related to blood vessels in the brain
• you have ever fainted or suddenly lost consciousness (syncope)
• you have a fever or an infection
• you have an immune system that does not function properly, due to an illness or because you are taking medicines that weaken your immune system
• you have never had chickenpox or have not been vaccinated against chickenpox. Your doctor may perform a blood test to check for the chickenpox virus. You may need to complete a full course of chickenpox vaccination and then wait 1 month before starting Ponvory
• you have breathing 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 oedema (see below) is higher in patients with diabetes
• you have eye problems, especially inflammation of the eye called uveitis
• you have high blood pressure

If you are in any of the above situations (or are unsure), consult your doctor before starting Ponvory.

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

Slow 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) must be performed before taking your first dose of Ponvory, or before restarting Ponvory after an interruption in treatment.

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

Infections

Ponvory may increase your risk of serious, life-threatening infections. Ponvory reduces the number of lymphocytes in your blood. These cells fight infections. Usually, their number returns to normal during the week after stopping treatment. Your doctor should check your blood cell count in a recent blood test before you start taking Ponvory.

Tell your doctor immediately if you experience any of the following signs of 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, neck stiffness, sensitivity to light, nausea, confusion (these may be symptoms of meningitis, an infection of the lining around your brain and spinal cord).

Macular oedema

Ponvory may cause a vision problem called macular oedema (fluid accumulation in the back of the eye (retina), which may cause changes in vision, including blindness).

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

Your doctor should check your vision before you start taking Ponvory and also each time you notice changes in your vision during treatment. Your risk of macular oedema is higher if you have diabetes or 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 visual field
• a blind spot in the center of your visual field
• sensitivity to light
• unusually colored (tinted) vision.

Liver problems

Ponvory may cause liver problems. Your doctor should perform blood tests to monitor your liver function before you start taking Ponvory.

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

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

Increased blood pressure

Since Ponvory may increase your blood pressure, your doctor should monitor it periodically during treatment with Ponvory.

Sun exposure and sun protection

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

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

Breathing problems

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

Swelling and narrowing of blood vessels in your brain

Use of medicines that work similarly to Ponvory has caused a condition called PML (posterior reversible encephalopathy syndrome, PRES). Symptoms of PRES usually improve when you stop taking Ponvory. However, if untreated, it may lead to stroke.

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

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

Worsening of multiple sclerosis after stopping Ponvory

When Ponvory treatment is stopped, MS symptoms may return. They may worsen compared to the condition before or during treatment. Always consult your doctor before stopping Ponvory. Inform your doctor if your MS symptoms worsen after stopping Ponvory.

Children and adolescents

Ponvory has not been studied in children or adolescents, so its use is not recommended in individuals under 18 years of age.

Other medicines and Ponvory

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including prescription and non-prescription medicines, vitamins and herbal supplements. Especially tell your doctor if you are taking:

• medicines to control heart rhythm (antiarrhythmics), blood pressure (antihypertensives), or heartbeats (such as calcium channel blockers or beta-blockers that may reduce 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 any vaccine or if you plan to receive a vaccine. You should avoid receiving live vaccines during treatment with Ponvory. If you receive a live vaccine, you may contract the infection the vaccine was intended to prevent. Treatment with Ponvory should be suspended 1 week before and for 4 weeks after administration of a live vaccine.

In addition, other vaccines may not work properly if given during treatment with Ponvory.

Pregnancy, contraception and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnancy

• Do not use Ponvory during pregnancy. If Ponvory is used during pregnancy, there is a risk of harm to the unborn baby.
• Do not use it if you are trying to become pregnant or if you are a woman of childbearing potential and are not using an effective contraceptive method.

Women of childbearing potential/contraception in women

If you are a woman of childbearing potential:

• Your doctor will inform you about the risk of harm to the unborn baby before starting Ponvory treatment, and a pregnancy test should be performed to confirm you are not pregnant.
• You must use an effective contraceptive method while taking Ponvory and also for 1 week after stopping it.

Talk to your doctor about reliable contraceptive methods.

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

If you become pregnant within 1 week after stopping Ponvory, speak with your doctor.

Breastfeeding

You must not breastfeed while taking Ponvory. This is to avoid the risk of adverse effects in the baby, as Ponvory may pass into breast milk.

Driving and using machines

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

Ponvory contains lactose

This medicine contains lactose, which is a type of sugar. If your doctor has informed you that you have an intolerance to certain sugars, consult with 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 exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

How to take it

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

Treatment initiation pack (14 days)

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

Day of treatment start from the pack	Daily dose
Day 1	2 mg
Day 2	2 mg
Day 3	3 mg
Day 4	3 mg
Day 5	4 mg
Day 6	4 mg
Day 7	5 mg
Day 8	6 mg
Day 9	7 mg
Day 10	8 mg
Day 11	9 mg
Day 12	10 mg
Day 13	10 mg
Day 14	10 mg

Maintenance dose

• After finishing the tablets from the starter pack, continue treatment with the maintenance dose of 20 mg.
• Record the date when you start taking the 20 mg maintenance dose next to week 1 of the Ponvory 20 mg blister pack.

If you take more Ponvory than you should

If you have taken more Ponvory than you should, inform 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 miss up to 3 consecutive doses of Ponvory while taking the starter pack or the maintenance dose, you may continue treatment by taking the first missed dose. Take 1 tablet as soon as you remember, then take 1 tablet daily to continue with the dose from the starter pack or the maintenance dose as planned.
• If you miss 4 or more consecutive doses of Ponvory while taking the starter pack or the maintenance dose, you must restart treatment with a new 14-day starter pack. Inform your doctor immediately if you miss 4 or more doses of Ponvory.

Record the date when you start taking the medicine so you know if you have missed 4 or more consecutive doses.

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

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects may be or may become serious.

Immediately inform your doctor or pharmacist if you notice any of the following side effects, as they may be signs of serious effects:

Common (may affect up to 1 in 10 people)

• urinary tract infection
• bronchitis
• flu (influenza)
• viral infection of nose, throat or chest (viral respiratory tract infection)
• viral infection
• infection by the herpes zoster virus (shingles)
• lung infection (pneumonia)
• sensation that everything is spinning (vertigo)
• fever (pyrexia)
• fluid accumulation at the back of the eye (retina) which may cause changes in vision, including blindness (macular edema)
• seizures (convulsions)

Uncommon (may affect up to 1 in 100 people)

• slow heart rate (bradycardia)

Other side effects

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

• infection of nose, sinuses or throat (nasopharyngitis, respiratory tract infection)
• increased levels of liver enzymes in the blood (a sign of liver problems)

Common (may affect up to 1 in 10 people)

• high blood pressure (hypertension)
• back pain
• feeling very tired (fatigue)
• dizziness
• difficulty breathing (dyspnea)
• high cholesterol level in the blood (hypercholesterolemia)
• joint pain (arthralgia)
• pain in arms or legs
• depression
• difficulty sleeping (insomnia)
• cough
• itching, runny or stuffy nose (rhinitis), infected or irritated throat (pharyngitis, laryngitis), sinus infection (sinusitis)
• feeling anxious (anxiety)
• decreased sensation or sensitivity, especially in the skin (hypoesthesia)
• increase in the level of a protein in the blood that may indicate infection or inflammation (increase in C-reactive protein level)
• drowsiness (somnolence)
• indigestion (dyspepsia)
• swollen hands, ankles or feet (peripheral edema)
• migraine
• ligament sprain
• chest discomfort
• low number of a type of white blood cells called lymphocytes (lymphopenia)

Uncommon (may affect up to 1 in 100 people)

• high level of potassium in the blood (hyperkalemia)
• swollen joint
• dry mouth

Reporting of side effects

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

5. Storage of Ponvory

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ponvory

• The active substance is ponesimod.

• The other ingredients are:

Tablet core

Croscarmellose sodium, 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)

Description of the product and contents of the pack

Ponvory 2 mg film-coated tablets are white, round, biconvex, film-coated tablets, 5 mm in diameter, marked with “2” on one side and an arch on the other side.

Ponvory 3 mg film-coated tablets are red, round, biconvex, film-coated tablets, 5 mm in diameter, marked with “3” on one side and an arch on the other side.

Ponvory 4 mg film-coated tablets are purple, round, biconvex, film-coated tablets, 5 mm in diameter, marked with “4” on one side and an arch on the other side.

Ponvory 5 mg film-coated tablets are green, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “5” on one side and an arch and an “A” on the other side.

Ponvory 6 mg film-coated tablets are white, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “6” on one side and an arch and an “A” on the other side.

Ponvory 7 mg film-coated tablets are red, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “7” on one side and an arch and an “A” on the other side.

Ponvory 8 mg film-coated tablets are purple, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “8” on one side and an arch and an “A” on the other side.

Ponvory 9 mg film-coated tablets are brown, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “9” on one side and an arch and an “A” on the other side.

Ponvory 10 mg film-coated tablets are orange, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “10” on one side and an arch and an “A” on the other side.

Ponvory 20 mg film-coated tablets are yellow, round, biconvex, film-coated tablets, 8.6 mm in diameter, marked with “20” on one side and an arch and an “A” on the other side.

Ponvory starter pack (pack configuration)

Each blister pack containing 14 film-coated tablets for a 2-week titration regimen includes:

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 pack) (pack configuration)

Pack containing 28 film-coated tablets for a 4-week treatment regimen, or multiple pack containing 84 tablets (3 packs of 28) for a 12-week treatment regimen.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

LABORATOIRES JUVISE PHARMACEUTICALS
149 Boulevard Bataille de Stalingrad
69100 Villeurbanne
France

Manufacturers

Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Patheon France
40 Boulevard De Champaret
38300 Bourgoin Jallieu
France

Creapharm Industry
29 rue Leon Faucher
51100 Reims
France

Date of the most recent 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