MAYZENT 0.25 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Mayzent 0.25 mg film-coated tablets

Mayzent 1 mg film-coated tablets

Mayzent 2 mg film-coated tablets

siponimod

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

1. What is Mayzent and what is it used for

What is Mayzent

Mayzent contains the active substance siponimod. Siponimod belongs to a group of medicines called sphingosine 1-phosphate receptor modulators (S1P).

What Mayzent is used for

Mayzent is used to treat adults with secondary progressive multiple sclerosis (SPMS) with active disease. In active disease in SPMS, there are still relapses or MRI (magnetic resonance imaging) scan results show signs of inflammation.

How Mayzent works

Mayzent helps protect the central nervous system (CNS) from attacks by the body's own immune system. It does this by:

• making some white blood cells in the blood (called lymphocytes) less able to move freely within the body, and
• preventing these cells from reaching the brain and spinal cord.

This reduces nerve damage caused by SPMS and as a result, Mayzent helps slow down the effects of disease activity (such as worsening disability, brain lesions, and relapses).

2. What you need to know before you take Mayzent

Do not take Mayzent

• if you are allergic to siponimod, peanut, soy, or any of the other ingredients of this medicine (listed in section 6).
• if you have an immunodeficiency syndrome.
• if you have ever had progressive multifocal leukoencephalopathy (PML) or cryptococcal meningitis.
• if you have active cancer.
• if you have severe liver problems.
• if you have had a heart attack, unstable angina, stroke, or any type of heart failure in the last 6 months.
• if you have any type of irregular or abnormal heartbeat (arrhythmia) and do not have a pacemaker.
• if blood tests show that your body cannot break down this medicine well enough, you should not take it (see "Blood tests before and during treatment" below).
• if you are pregnant or could become pregnant and are not using an effective contraceptive method.

Warnings and precautions

Tell your doctor beforeyou start taking Mayzent:

• if you have an infection or if your immune system is not working properly (for example, due to a disease or medicines that suppress the immune system; see also "Other medicines and Mayzent").
• if you have never had chickenpox and have not been vaccinated against it. If you develop chickenpox while taking Mayzent, you may be at increased risk of complications. Your doctor may want to vaccinate you against chickenpox before you start treatment.
• if you are scheduled to receive any vaccine. Your doctor will advise you on this (see "Other medicines and Mayzent").
• if you have ever had problems with your vision (in particular, a condition called macular edema) or an infection or inflammation in the eye (uveitis). Your doctor may want to perform eye exams before starting treatment and regularly during treatment. Mayzent can cause inflammation of the macula (the part of the eye that allows you to see shapes, colors, and details) known as macular edema. The likelihood of developing macular edema is higher if you have had macular edema before or if you have ever had uveitis (inflammation in the eye).
• if you have diabetes. The likelihood of developing macular edema (see above) is higher in patients with diabetes.
• if you have ever had any of the following conditions (even if you are being treated for them): severe heart disease, irregular or abnormal heartbeat (arrhythmia), stroke, or other conditions related to the blood vessels in the brain, slow heart rate, fainting, or abnormal heart rhythm (as indicated by abnormal ECG results).
• if you have severe respiratory problems when sleeping (sleep apnea).
• if you have high blood pressure that cannot be controlled with medicines. You will need to have your blood pressure checked regularly.
• if you have ever had liver problems. Your doctor may want to perform blood tests to check your liver function before prescribing Mayzent.
• if you could become pregnant, as siponimod may harm the fetus when used during pregnancy. Before starting treatment, your doctor will explain the risk to you and ask you to have a pregnancy test to make sure you are not pregnant. During treatment and for at least 10 days after stopping treatment, you must use an effective contraceptive method (see "Pregnancy, breastfeeding, and fertility").

If any of the above applies to you, tell your doctor beforetaking Mayzent.

Monitor the following while taking Mayzent

If you experience any of the following symptoms while taking Mayzent, tell your doctor immediatelyas they may be serious:

• if you have an infection. Mayzent decreases the number of white blood cells in the blood. White blood cells fight infections, so during treatment with Mayzent (and up to 3-4 weeks after stopping treatment), you may be more likely to get infections. This could be serious and even life-threatening.
• if you think your multiple sclerosis (MS) is getting worse or if you notice any new or unusual symptoms. A rare brain infection called progressive multifocal leukoencephalopathy (PML) can cause symptoms similar to those of SPMS. It can occur in patients taking medicines like Mayzent and other medicines used to treat MS. If PML is confirmed, your doctor will stop your treatment with Mayzent. Some people may have a reaction when Mayzent is removed from the body. This reaction (known as immune reconstitution inflammatory syndrome or IRIS) can cause worsening of your disease, including worsening of brain function.
• if you have a fever, feel like you have the flu, or have a headache with stiff neck, sensitivity to light, nausea, or confusion. These can be symptoms of meningitis and/or encephalitis caused by a fungal or viral infection (such as cryptococcal meningitis).
• if you notice changes in your vision, such as if the center of your field of vision becomes blurry or shadowy, a blind spot appears in the center of your field of vision, or you have trouble seeing colors or small details. These can be symptoms of macular edema. In the early stages of macular edema, you may not have any symptoms, and it can cause some of the same visual symptoms as an MS relapse (optic neuritis). Your doctor may want you to have an eye exam 3-4 months after starting treatment and possibly repeat it later. If macular edema is confirmed, your doctor may advise you to stop treatment with Mayzent.
• if you experience symptoms such as sudden severe headache, confusion, seizures, and changes in vision. These can be symptoms of a condition called posterior reversible encephalopathy syndrome (PRES).
• if you have symptoms such as nausea, vomiting, abdominal pain, fatigue, yellowing of the skin or the white part of the eye, or unusually dark urine, without any apparent cause. These can be symptoms of liver problems.
• if you notice any nodules on the skin (e.g., shiny nodules with a pearl-like appearance), spots, or open sores that do not heal within weeks.

Slow heart rate (bradycardia) and irregular heartbeats

During the first few days of treatment, Mayzent may cause a decrease in heart rate (bradycardia). You may not notice anything or you may feel dizzy or tired. It can also cause irregular heartbeats at the start of treatment. If there is any indication that you may be at increased risk of these effects, your doctor may decide to monitor you more closely at the start of treatment, refer you to a heart specialist (cardiologist), or not prescribe Mayzent for you.

Tests before and during treatment

The speed at which this medicine is broken down (metabolized) in the body varies from person to person, and therefore different people need different doses. Your doctor will perform a blood or saliva test before starting treatment to determine the best dose for you. In rare cases, the test result may indicate that you should not take Mayzent.

• Blood count

The expected effect of treatment with Mayzent is to decrease the number of white blood cells in the blood. This decrease usually returns to normal within 3-4 weeks after stopping treatment. If you need to have any blood tests, tell your doctor that you are taking Mayzent. Otherwise, the results may not be clear to the doctor, and depending on the type of blood test, a larger blood sample may be needed.

Before starting treatment with Mayzent, your doctor will check if you have a sufficient number of white blood cells in your blood and may want to repeat this check periodically. If you do not have a sufficient number of white blood cells, your doctor may ask you not to take Mayzent or to reduce the dose.

Before starting treatment, you will also have a blood test to check that your liver is working properly.

Skin cancer

There have been reports of skin cancer in patients with MS who have been treated with Mayzent. Tell your doctor immediately if you notice any nodules on the skin (e.g., shiny nodules with a pearl-like appearance), spots, or open sores that do not heal within weeks. Symptoms of skin cancer can include abnormal growth or changes in skin tissue (e.g., unusual moles) that change color, shape, or size over time. Before starting treatment with Mayzent, a skin exam is required to check if you have any nodules on the skin. Your doctor will also perform regular skin checks during treatment with Mayzent. If any skin problems occur, your doctor may refer you to a dermatologist, who may decide that it is important to see you regularly.

Sun exposure and sun protection

Mayzent weakens your immune system. This can increase your risk of developing skin cancer. You should limit your exposure to the sun and UV rays by:

• wearing protective clothing.
• applying a high UV protection sunscreen regularly.

Worsening of MS after stopping Mayzent treatment

Do not stop taking Mayzent or change the dose you have been prescribed without talking to your doctor first.

Tell your doctor immediately if you think your MS is getting worse after stopping treatment with Mayzent (see "If you stop taking Mayzent" in section 3).

Elderly patients (65 years of age and older)

There is no experience with Mayzent in elderly patients. Talk to your doctor if you have any concerns.

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age, as it has not been studied in this age group.

Other medicines and Mayzent

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Make sure to tell your doctor if you are taking or receiving any of the following medicines or therapies:

• medicines for irregular heartbeats, such as amiodarone, procainamide, quinidine, or sotalol. Your doctor may decide not to prescribe Mayzent because they may increase the effect on irregular heartbeats.
• medicines that slow down heartbeats, such as diltiazem or verapamil (which belong to a group of medicines called calcium channel blockers), digoxin, or ivabradina. Your doctor may refer you to a heart specialist, as it may be necessary to change your medicines because Mayzent can also slow down heartbeats during the first few days of treatment. If you are taking a beta-blocker, such as atenolol or propranolol, your doctor may ask you to stop beta-blocker treatment temporarily until you have reached your full daily dose of Mayzent.
• medicines that affect the immune system, such as chemotherapy, immunosuppressants, or other medicines used to treat MS. Your doctor may ask you to stop taking these treatments to avoid increasing the effect on the immune system.
• vaccines. If you need to receive a vaccine, talk to your doctor first. During treatment with Mayzent and for 4 weeks after stopping treatment, you should not receive certain types of vaccines (called live attenuated vaccines) because they can cause the infections they are meant to prevent (see section 2).
• fluconazole and other medicines that can increase Mayzent levels in the blood and are not recommended to be taken with Mayzent. Your doctor will inform you about this.
• carbamazepine and other medicines that can decrease Mayzent levels in your blood and prevent it from working properly. Your doctor will inform you about this.
• modafinil and other medicines that can decrease Mayzent levels in your blood in some patients and prevent it from working properly. Your doctor will inform you if this applies to you.
• UV radiation therapy or PUVA photochemotherapy. UV therapy during treatment with Mayzent can increase your risk of developing skin cancer.

Pregnancy, breastfeeding, and fertility

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

Do not use Mayzent during pregnancy, or if you are planning to become pregnant, or if you are a woman who could become pregnant and are not using an effective contraceptive method. If Mayzent is used during pregnancy, it can cause harm to the fetus. If you are a woman who could become pregnant, your doctor will inform you about this risk before starting treatment with Mayzent and will ask you to have a pregnancy test to make sure you are not pregnant. You must use an effective contraceptive method during treatment with Mayzent and for at least 10 days after stopping treatment to avoid becoming pregnant. Talk to your doctor about reliable contraceptive methods.

If you become pregnant during treatment with Mayzent, tell your doctor immediately. Your doctor will decide to stop treatment (see "If you stop taking Mayzent" in section 3). You will receive specific prenatal monitoring.

Do not breastfeed during treatment with Mayzent. Mayzent can pass into breast milk and there is a risk of serious side effects for the baby.

Driving and using machines

Your doctor will tell you if your disease allows you to drive and use machines safely. It is not expected that Mayzent will affect your ability to drive and use machines when you are on the regular treatment dose. At the start of treatment, you may occasionally feel dizzy. Therefore, on the first day of treatment with Mayzent, do not drive or use machines.

Mayzent contains lactose and soy lecithin

If your doctor has told you that you have an intolerance to some sugars, talk to your doctor before taking this medicine.

If you are allergic to peanut or soy, do not use this medicine.

3. How to take Mayzent

Treatment with Mayzent will be supervised by a doctor with experience in the treatment of MS.

Follow the administration instructions of this medicine exactly as indicated by your doctor.

In case of doubt, consult your doctor again.

How much Mayzent to take

Starting treatment

You will be given a dosage adjustment package with which your dose will be gradually increased over 5 days. Follow the instructions on the package (see also the "Dosage Adjustment Package" table).

The purpose of the dosage adjustment period is to reduce the risk of adverse reactions in the heart at the start of treatment. Your doctor may closely monitor you at the start of treatment if you are at risk of your heartbeat becoming slower or irregular.

Dosage Adjustment Package

On day 6, you will start taking your regular treatment dose.

For the first 6 days of treatment, it is recommended to take the tablets in the morning with or without food.

Treatment dose

The recommended dose is 2 mg once a day (one 2 mg Mayzent tablet) with or without food.

Your doctor may indicate that you take only 1 mg once a day (one Mayzent 1 mg tablet or four Mayzent 0.25 mg tablets) if the blood test performed before starting treatment showed that your body breaks down Mayzent slowly (see "Tests before and during treatment"). However, if this is your case, note that it is safe to take five 0.25 mg tablets on day 5 of the dosage adjustment period as indicated above.

Mayzent is administered orally. Take the tablet with water.

If you take more Mayzent than you should

If you have taken too many Mayzent tablets, or if you mistakenly took the first tablet from the package with the treatment dose instead of the dosage adjustment package, talk to your doctor immediately. He or she may decide to keep you under observation.

If you forget to take Mayzent

If you forget to take your dose during the first 6 days of treatment, talk to your doctor before taking the next dose. Your doctor will have to prescribe a new dosage adjustment package. You will have to restart treatment with day 1.

If you forget to take a dose when you are on the regular treatment dose (day 7 onwards), take it as soon as you realize. If it is almost time to take the next dose, do not take the missed dose and continue with the usual intake schedule. Do not take a double dose to make up for missed doses. If you forget to take Mayzent for 4 or more consecutive days, talk to your doctor before taking the next dose. Your doctor will have to prescribe a new dosage adjustment package, and you will have to restart treatment with day 1.

If you stop treatment with Mayzent

Do not stop treatment with Mayzent or change your dose without discussing it with your doctor first.

Mayzent will remain in your body until 10 days after you stop treatment. The number of white blood cells (lymphocytes) in your blood may remain low for a period of up to 3 to 4 weeks after stopping treatment with Mayzent. It is possible that the adverse effects described in this leaflet may still appear during this period (see "Possible side effects" in section 4).

If you have to restart treatment with Mayzent after a pause of more than 4 days after stopping it, your doctor will prescribe a new dosage adjustment package, and you will have to restart treatment with day 1.

Tell your doctor immediately if you think your MS has worsened after stopping treatment with Mayzent.

If you have any other 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 everybody gets them.

Serious side effects

Common(may affect up to 1 in 10 patients)

• Rash with small blisters filled with fluid, which appear on reddened skin (symptoms of a viral infection called herpes zoster, which can be severe)
• A type of skin cancer known as basal cell carcinoma (BCC) that often presents as a pearl-like nodule, although it can also have other forms.
• Fever, sore throat, and/or mouth ulcers due to an infection (lymphopenia)
• Seizures, attacks
• Visual disturbances such as a shadow or blind spot in the center of the visual field, blurred vision, problems seeing colors or details (symptoms of macular edema, which is an inflammation in the macula area of the retina in the back of the eye)
• Irregular heartbeat (atrioventricular block)
• Slow heartbeat (bradycardia)

Uncommon(may affect up to 1 in 100 patients)

• A type of skin cancer known as squamous cell carcinoma that can present as a firm red nodule, an ulcer with a crust, or a new ulcer on an existing scar
• A type of skin cancer known as malignant melanoma that usually develops from an unusual mole. Possible signs of melanoma include moles that change in size, shape, thickness, or color over time, or the formation of new moles. Moles can be itchy, bleed, or ulcerate.

Rare(may affect up to 1 in 1,000 patients)

• A brain infection called progressive multifocal leukoencephalopathy (PML). The symptoms of PML can be similar to those of MS, such as weakness or changes in vision, memory loss, problems thinking, or difficulty walking.
• An inflammatory disorder after stopping treatment with Mayzent (known as immune reconstitution inflammatory syndrome or IRIS).

Frequency not known(cannot be estimated from the available data)

• Cryptococcal infections (a type of fungal infection) or viral infections (caused by the herpes or varicella-zoster virus), including meningitis and/or encephalitis with symptoms such as headache along with neck stiffness, sensitivity to light, feeling unwell (nausea) or confusion

If you have any of these symptoms, tell your doctor immediately.

Other side effects

Other side effects include those listed below. If any of these side effects become severe, tell your doctor or pharmacist.

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

• headache
• high blood pressure (hypertension), sometimes with symptoms such as headache and dizziness
• blood test results showing increased levels of liver enzymes

Common(may affect up to 1 in 10 patients)

• new moles
• dizziness
• involuntary body movements (tremor)
• diarrhea
• feeling unwell (nausea)
• pain in the hands or feet
• swelling of hands, ankles, legs, or feet (peripheral edema)
• weakness (asthenia)
• lung function test results showing decreased function

Reporting side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects that are not listed in this leaflet. You can 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 Mayzent

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

Do not use this medicine after the expiration date that appears on the box after "EXP" and on the blister after "EXP". The expiration date is the last day of the month indicated.

Do not store above 25°C.

Do not use this medicine if you notice that the package is damaged or shows signs of having been tampered with.

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

6. Package contents and additional information

Composition of Mayzent

• The active ingredient is siponimod.

Mayzent 0.25 mg film-coated tablets

• Each tablet contains 0.25 mg of siponimod (as siponimod fumaric acid).
• The other ingredients are:

Tablet core: lactose monohydrate (see "Mayzent contains lactose and soy lecithin" in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Tablet coating: polyvinyl alcohol, titanium dioxide (E171), red iron oxide (E172), black iron oxide (E172), talc, soy lecithin (see "Mayzent contains lactose and soy lecithin" in section 2), xanthan gum.

Mayzent 1 mg film-coated tablets

• Each tablet contains 1 mg of siponimod (as siponimod fumaric acid).
• The other ingredients are:

Tablet core: lactose monohydrate (see "Mayzent contains lactose and soy lecithin" in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Tablet coating: polyvinyl alcohol, titanium dioxide (E171), red iron oxide (E172), black iron oxide (E172), talc, soy lecithin (see "Mayzent contains lactose and soy lecithin" in section 2), xanthan gum.

Mayzent 2 mg film-coated tablets

• Each tablet contains 2 mg of siponimod (as siponimod fumaric acid).
• The other ingredients are:

Tablet core: lactose monohydrate (see "Mayzent contains lactose and soy lecithin" in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Tablet coating: polyvinyl alcohol, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), talc, soy lecithin (see "Mayzent contains lactose and soy lecithin" in section 2), xanthan gum.

Appearance of the product and package contents

Mayzent 0.25 mg film-coated tablets are round, pale red, film-coated tablets with the company logo on one side and "T" on the other side.

Mayzent 1 mg film-coated tablets are round, pale violet, film-coated tablets with the company logo on one side and "L" on the other side.

Mayzent 2 mg film-coated tablets are round, pale yellow, film-coated tablets with the company logo on one side and "II" on the other side.

Mayzent 0.25 mg film-coated tablets are available in the following package sizes:

• Dosage adjustment package in the form of a box containing 12 tablets, and
• Packages containing 84 or 120 tablets

Mayzent 1 mg film-coated tablets are available in packages containing 28 or 98 tablets.

Mayzent 2 mg film-coated tablets are available in packages containing 14, 28, or 98 tablets.

Not all package sizes may be marketed.

Marketing authorization holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nuremberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

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