Product 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 this entire product information carefully before starting to take this medicine, as it contains important information for you.

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

What is Mayzent

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

What is Mayzent used for

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

How Mayzent works

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

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

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

Do not take Mayzent

• if you are allergic to siponimod, peanuts, soy, or any of the other ingredients of this medicine (listed in section 6).
• if you have immunodeficiency syndrome.
• if you have ever had progressive multifocal leukoencephalopathy 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 heart rhythm (arrhythmia) and do not have a pacemaker.
• if blood tests show that your body cannot break down this medicine well enough, do 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

Consult your doctorbeforestarting to take Mayzent:

• if you have an infection or if your immune system does not work 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 during treatment with Mayzent, you may have a higher risk of developing complications. Your doctor may want to vaccinate you against chickenpox before you start treatment.
• if you are planning to receive any vaccine. Your doctor will advise you (see "Other medicines and Mayzent").
• if you have ever had, or have, vision problems (in particular a condition called macular edema) or an eye infection or inflammation (uveitis). Your doctor may want to perform eye examinations before starting treatment and regularly during treatment. Mayzent can cause macular edema (inflammation of the macula, the area of the eye that allows you to see shapes, colors, and details). The risk of developing macular edema is higher if you have had macular edema before or if you have ever had uveitis.
• if you have diabetes. The risk of developing macular edema (see previous point) is higher in patients with diabetes.
• if you have ever had any of the following conditions (although you are receiving treatment for them): severe heart disease, irregular or abnormal heart rhythm (arrhythmia), stroke (cerebral vasculitis), or other diseases related to blood vessels in the brain, slow heart rate, fainting, or abnormal heart rhythm (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 have to control your blood pressure 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 can cause harm to the fetus when used during pregnancy. Before starting treatment, your doctor will explain the risk and ask you to have a pregnancy test to ensure you are not pregnant. During treatment and for 10 days after stopping treatment, you must use an effective contraceptive method (see "Pregnancy, breastfeeding, and fertility").

If any of the above cases apply to you, inform your doctorbeforetaking Mayzent.

Be aware of the following while taking Mayzent

If you experience any of the following symptoms while taking Mayzent,inform your doctorimmediatelyas it could be serious:

• if you have an infection. Mayzent reduces the number of white blood cells in the blood. White blood cells fight infections, so during treatment with Mayzent (and up to 3 to 4 weeks after stopping it) you may be more susceptible to infections, which could be severe or even life-threatening.
• if you think your multiple sclerosis (MS) is getting worse or if you notice any new or unusual symptoms. A rare infection of the brain called progressive multifocal leukoencephalopathy (PML) can cause symptoms similar to those of MS. It can occur in patients taking medicines like Mayzent and other medicines used to treat MS.
• if you have fever, feel like you have the flu, or have headache along with neck stiffness, sensitivity to light, nausea, or confusion. These may 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 blurred vision in the center of your field of vision, a blind spot in the center of your field of vision, or problems seeing colors or small details. These may be symptoms of macular edema. In the early stages of macular edema, you may not have any symptoms and may cause some of the same visual symptoms as a MS relapse (optic neuritis). Your doctor may want to perform eye examinations 3 or 4 months after starting treatment and possibly repeat them later. If macular edema is confirmed, your doctor may advise you to stop treatment with Mayzent.
• if you experience symptoms such as sudden onset of severe headache, confusion, seizures, and changes in vision. These may be symptoms of a condition called reversible posterior leukoencephalopathy syndrome (RPLS).
• if you experience symptoms such as nausea, vomiting, abdominal pain, fatigue, yellowing of the skin or eyes, or dark urine without apparent cause. These may be symptoms of liver problems.
• if you notice any skin nodules (e.g., shiny nodules with a pearl-like appearance), spots, or open wounds that do not heal within weeks.

Abnormal heart rhythm (bradycardia) and irregular heartbeats

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

Blood tests before and during treatment

The rate 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 test 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.

• Complete blood count

The expected effect of treatment with Mayzent is to reduce the number of white blood cells in the blood.Generally, this decrease returns to normal values between 3 and 4weeks after stopping treatment. If you need to have any blood tests, inform your doctor that you are taking Mayzent. Otherwise, the results may not be clear for the doctor, and depending on the type of blood test, you may need to have a larger blood sample taken.

Before starting treatmentwith Mayzent, your doctor will confirm that you have a sufficient number of white blood cells in your bloodandmay want to repeat this control 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, a blood test will also be performed to check that your liver is functioning properly.

Skin cancer

Several cases of skin cancer have been reported in patients with MS who have been treated with Mayzent. Inform your doctor immediately if you notice any skin nodules (e.g., shiny nodules with a pearl-like appearance), spots, or open wounds that do not heal within weeks. The symptoms of skin cancer may include abnormal growth or changes in the skin tissue (e.g., unusual moles) that over time change color, shape, or size. Before starting treatment with Mayzent, a skin examination is required to check if you have any skin nodules. Your doctor will also perform regular skin checks during treatment with Mayzent. If any skin problems appear, your doctor may refer you to a dermatologist, who may decide that it is necessary to see you regularly.

Exposure to the sun and sun protection

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

• wearing protective clothing.
• regularly applying a high-protection sunscreen cream.

Worsening of MS after stopping treatment with Mayzent

Do not stop taking Mayzent or change the dose prescribed by your doctor without discussing it with your doctor first.

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

Older patients (65 years of age and older)

There is no experience with Mayzent in older patients. Consult your doctor if you have any concerns.

Children and adolescents

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

Other medicines and Mayzent

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine. Make sure to inform your doctor if you are taking or receiving any of the following medicines or therapies:

• medicines to treat irregular heartbeats, such as amiodarone, procainamide, quinidine, or sotalol. Your doctor may decide not to prescribe Mayzent because they may intensify 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 ivabradine. 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 temporarily stop taking the beta-blocker 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 an increase in 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 up to 4 weeks after stopping treatment, certain types of vaccines (called live attenuated vaccines) should not be administered to you, as they may trigger the development of infections that the vaccines are intended to prevent (see section 2).
• fluconazole and other medicines that can increase the levels of Mayzent in the blood and are not recommended to be taken in combination with Mayzent. Your doctor will inform you about this.
• carbamazepine and other medicines that can decrease the levels of Mayzent in the blood and may prevent it from working properly. Your doctor will inform you about this.
• modafinil and other medicines that can decrease the levels of Mayzent in the blood in certain patients and may prevent it from working properly. Your doctor will inform you if this applies to you.
• phototherapy with UV radiation or PUVA photochemotherapy. UV therapy during treatment with Mayzent may increase your risk of developing skin cancer.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using 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 is not using an effective contraceptive method. If Mayzent is used during pregnancy, there is a risk of causing 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 ask you to have a pregnancy test to ensure 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. Consult your doctor about reliable contraceptive methods.

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

During treatment with Mayzent, do not breastfeed. Mayzent may pass into breast milk and there is a risk of severe adverse effects for the baby.

Driving and using machines

Your doctor will inform you if your disease allows you to drive vehicles and use machines safely. Mayzent is not expected to affect your ability to drive and use machines when taking the regular treatment dose. On the first day 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 certain sugars, consult them before taking this medicine.

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

The treatment with Mayzent will be supervised by a doctor with experience in treating MS.

Follow exactly the administration instructions of this medication 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 dose adjustment package with which your dose will gradually increase over 5 days. Follow the instructions that appear in the package (see also the "Dose adjustment package" table).

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

Dose adjustment package

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

During 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 (1 Mayzent 2 mg tablet) with or without food.

Your doctor may instruct you to take only 1 mg once a day (1 Mayzent 1 mg tablet or 4 Mayzent 0.25 mg tablets) if the blood test performed before starting treatment showed that your body breaks down Mayzent slowly (see "Blood tests before and during treatment"). However, if this is your case, note that it is safe to take 5 Mayzent 0.25 mg tablets on day 5 of the dose adjustment period as indicated earlier.

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 by mistake the first tablet you took was from the treatment dose package instead of the dose adjustment package, speak immediately with your doctor. Your doctor may decide to keep you under observation.

If you forget to take Mayzent

If during the first 6 days of treatment you forget to take your dose one day, speak with your doctor before taking the next dose. Your doctor will have to prescribe a new dose adjustment package. You will have to restart the 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 remember. If it is almost time to take the next dose, do not take the missed dose and continue with the usual dosing schedule. Do not take a double dose to make up for the missed doses. If you forget to take Mayzent for 4 or more consecutive days, speak with your doctor before taking the next dose. Your doctor will have to prescribe a new dose adjustment package and you will have to restart the treatment with day 1.

If you interrupt treatment with Mayzent

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

Mayzent will remain in your body for up to 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 adverse effects" in section 4).

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

Inform 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 medication, ask your doctor or pharmacist.

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

Severe side effects

Frequent(may affect up to 1 in 10 patients)

• Rash with small blisters filled with fluid, appearing on red skin (symptoms of a viral infection called herpes zoster, which can be serious)
• A type of skin cancer known as basal cell carcinoma (CCB) 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 inflammation in the macula area of the retina at the back of the eye)
• Irregular heartbeat (atrioventricular block)
• Slow heartbeat (bradycardia)

Not frequent(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, a sore with a scab, or a new sore 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 over time can change in size, shape, thickness, or color, or the formation of new moles. Moles can cause itching, bleeding, or ulceration

Rare(may affect up to 1 in 10,000 patients)

• A brain infection called progressive multifocal leukoencephalopathy (PML). Symptoms of PML can be similar to MS, such as weakness or changes in vision, memory loss, problems thinking, or difficulty walking

• Inflammatory disorder after interrupting treatment with Mayzent (known as immune reconstitution inflammatory syndrome or IRIS)

Frequency unknown(cannot be estimated from 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, neck stiffness, sensitivity to light, feeling unwell (nausea), or confusion

If you experience any of these symptoms,inform your doctor immediately.

Other side effects

Other side effects include the following. If any of these side effects become severe,inform your doctor or pharmacist.

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

• Headache
• High blood pressure (hypertension), sometimes with symptoms such as headache and dizziness
• Lab results showing an increase in liver enzyme levels

Frequent(may affect up to 1 in 10 patients)

• New moles
• Dizziness
• Unintentional body movements (tremor)
• Diarrhea
• Feeling unwell (nausea)
• Pain in the hands or feet
• Swelling of hands, ankles, legs, or feet (peripheral edema)
• Weakness (asthenia)
• Lab results showing decreased lung function

Reporting side effects

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

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

Do not use this medication after the expiration date that appears on the box after “CAD” and on the blister pack after “EXP”. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C.

Do not use this medication if you observe that the packaging is damaged or shows signs of having been manipulated.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medication that you no longer need. In this way, you will help protect the environment.

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 fumarate).
• The other components are:

Core of the tablet: Lactose monohydrate (see “Mayzent contains lactose and soy lecithin” in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Coating of the tablet: Polyvinyl alcohol, titanium dioxide (E171), iron oxide red (E172), iron oxide black (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 fumarate).
• The other components are:

Core of the tablet: Lactose monohydrate (see “Mayzent contains lactose and soy lecithin” in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Coating of the tablet: Polyvinyl alcohol, titanium dioxide (E171), iron oxide red (E172), iron oxide black (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 fumarate).
• The other components are:

Core of the tablet: Lactose monohydrate (see “Mayzent contains lactose and soy lecithin” in section 2), microcrystalline cellulose, crospovidone, glycerol dibehenate, anhydrous colloidal silica.

Coating of the tablet: Polyvinyl alcohol, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), talc, soy lecithin (see “Mayzent contains lactose and soy lecithin” in section 2), xanthan gum.

Appearance of the product and contents of the pack

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, violet-white 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 pack sizes:

• Blister pack containing 12 tablets, and
• Packs containing 84 or 120 tablets

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

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

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer responsible

Novartis Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nuremberg

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:https://www.ema.europa.eu