Mayzent

Package leaflet: Information for the patient

Mayzent 0.25 mg film-coated tablets, 1 mg film-coated tablets, 2 mg film-coated tablets

siponimod
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Mayzent is and what it is used for

What Mayzent is
Mayzent contains the active substance siponimod. Siponimod belongs to a group of medicines known as sphingosine-1-phosphate (S1P) receptor modulators.
What Mayzent is used for
Mayzent is used to treat adult patients with active secondary progressive multiple sclerosis (SPMS). In SPMS, active disease is present when there are still relapses or when MRI (magnetic resonance imaging) results show signs of inflammation.
How Mayzent works
Mayzent helps protect the central nervous system (CNS) from attacks by the immune system. This is achieved by:

• reducing the ability of certain white blood cells (lymphocytes) to circulate freely throughout the body, and
• preventing these cells from reaching the brain and spinal cord. This limits nervous system damage caused by SPMS, and consequently Mayzent helps slow the effects of disease activity (such as worsening disability, brain lesions, and relapses).

2. What you need to know before taking Mayzent

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 an 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 certain types of heart failure within the past 6 months
• if you have certain types of irregular or abnormal heartbeat (arrhythmia) and do not have a pacemaker
• if blood tests show that your body cannot sufficiently metabolize this medicine, you must not take it (see below section “Blood tests before and during treatment”)
• if you are pregnant or of childbearing age and are not using effective contraception.

Warnings and precautions
Talk to your doctor before 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 contract chickenpox during treatment with Mayzent, the risk of complications may be higher. Before starting treatment, your doctor may recommend that you get vaccinated against chickenpox
• if you are planning any vaccination. Your doctor will advise you (see “Other medicines and Mayzent”)
• if you have ever had or currently have vision problems (particularly a condition called macular edema) or an eye infection or inflammation (uveitis). Your doctor may ask you to have an eye examination before starting treatment and at regular intervals during treatment. Mayzent can cause swelling of the macula (the area of the eye that allows you to see shapes, colors, and fine details), known as macular edema. Your risk of developing macular edema is higher if you have had it before or if you have had eye inflammation called uveitis
• if you have diabetes. The risk 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 currently being treated for them): severe heart disease, irregular or abnormal heartbeat (arrhythmia), stroke or other disease affecting the blood vessels in the brain, slow heartbeat, fainting, or heart rhythm disorders (due to abnormal ECG results)
• if you suffer from severe breathing problems during sleep (sleep apnea)
• if you have high blood pressure that cannot be controlled with medication. Your blood pressure should be monitored regularly
• if you have ever had liver problems. Your doctor may ask you to have blood tests to check liver function before prescribing Mayzent
• if there is a possibility you could become pregnant, because siponimod may harm the unborn baby if used during pregnancy. Before starting treatment, your doctor will explain the risks to you and ask you to take a pregnancy test to make sure you are not pregnant. You must use effective contraception during treatment and for at least 10 days after stopping treatment (see “Pregnancy, breastfeeding and fertility”).

If any of these apply to you, inform your doctor before taking Mayzent.
Be cautious during treatment with Mayzent
If you experience any of the following symptoms while taking Mayzent, inform your doctor immediately as they may be serious:

• if you have an infection. Mayzent reduces the number of white blood cells in the blood. White blood cells fight infections, so infections may occur more easily during treatment with Mayzent (and up to 3–4 weeks after stopping treatment). Infections can be serious and may even be life-threatening.
• if you think your multiple sclerosis (MS) is worsening or if you notice any new or unusual symptoms. A rare brain infection called progressive multifocal leukoencephalopathy (PML) can cause symptoms similar to MS. This may occur in patients taking medicines similar to Mayzent and other medicines used to treat MS. If PML is confirmed, your doctor will stop treatment with Mayzent. Some people may have a reaction when Mayzent is cleared from the body. This reaction (known as immune reconstitution inflammatory syndrome or IRIS) may lead to worsening of their condition, including worsening brain function.
• if you develop fever, flu-like symptoms, or headache accompanied by neck stiffness, sensitivity to light, nausea and/or confusion. These may be symptoms of meningitis and/or encephalitis caused by a viral or fungal infection (such as cryptococcal meningitis)
• if you experience vision changes, for example, if your central vision becomes blurred or shadowy, a blind spot develops in your central vision, or you have difficulty distinguishing colors or fine details. These may be symptoms of macular edema. In the early stages of macular edema, there may be no symptoms, and macular edema may cause some of the visual symptoms that also occur during MS attacks (optic neuritis). Your doctor may ask you to have an eye examination 3–4 months after starting treatment and possibly again later. If macular edema is confirmed, your doctor may advise stopping treatment with Mayzent
• if you experience symptoms such as sudden severe headache, confusion, seizures, or vision changes. These may be symptoms of a condition called posterior reversible encephalopathy syndrome (PRES)
• if you experience symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, yellowing of the skin or whites of the eyes, or abnormally dark-colored urine. These may be symptoms of liver problems
• if you notice skin nodules (e.g., shiny, pearly nodules), spots, or open sores that do not heal within weeks.

Slow heart rate (bradycardia) and irregular heartbeat
During the first few days of treatment, Mayzent may cause a slowing of the heart rate (bradycardia), and you may feel nothing or experience dizziness or fatigue. At the start of treatment, Mayzent may also cause an irregular heartbeat. If there are factors indicating you may be at higher risk of these effects, your doctor may decide to monitor you more closely at the beginning of treatment, refer you to a cardiologist beforehand, or decide not to prescribe Mayzent.

Tests before and during treatment
The rate at which this medicine is processed (metabolized) by the body varies from patient to patient, so different people require different doses. Your doctor will perform a blood or saliva test before starting treatment to determine the optimal dose for you. In rare cases, blood test results may indicate that you should not take Mayzent.

• Complete blood count (CBC) The intended effect of Mayzent treatment is to reduce the number of white blood cells in the blood. These usually return to normal within 3–4 weeks after stopping treatment. If you need blood tests, inform your doctor that you are taking Mayzent. Otherwise, your doctor may not be able to interpret the test results correctly, and for certain blood tests, your doctor may need to draw more blood than usual.

Before starting Mayzent, your doctor will confirm that you have enough white blood cells in your blood and may repeat this check regularly. If your white blood cell count is too low, your doctor may decide to interrupt Mayzent treatment or reduce the dose.
Before starting treatment, you will also have blood tests to check how well your liver is working.

Skin cancers
Skin tumors have been reported in patients with MS treated with Mayzent. Talk to your doctor immediately if you notice skin nodules (e.g., shiny, pearly nodules), spots, or open sores that do not heal within weeks. Symptoms of skin cancer may include abnormal growths or changes in skin tissue (e.g., unusual moles) with changes in color, shape, or size over time. A skin examination is required before starting Mayzent to check for skin nodules. Your doctor will also perform regular skin examinations during treatment with Mayzent. If you develop skin problems, your doctor may refer you to a dermatologist, who may decide that regular monitoring is necessary.

Sun exposure and sun protection
Mayzent weakens the immune system. This may increase the risk of developing skin cancer. You should limit exposure to sunlight and UV rays:

• by wearing appropriate protective clothing
• by regularly applying sunscreen with high UV protection.

Worsening of MS after stopping Mayzent treatment
Do not stop taking Mayzent or change your dose without first talking to your doctor.
Inform your doctor immediately if you think your MS is worsening after stopping Mayzent treatment (see “If you stop taking Mayzent” in section 3).

Elderly patients (aged 65 years and older)
There is limited experience with Mayzent in elderly patients. If you have any doubts, talk to your doctor.

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
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Make sure to inform your doctor if you are taking or are being treated with any of the following medicines or therapies:

• medicines for irregular heartbeat, such as amiodarone, procainamide, quinidine, or sotalol. Your doctor may decide not to prescribe Mayzent, as it may intensify the effect on irregular heartbeat
• medicines that slow the heart rate, 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 cardiologist, as it may be necessary to change your current medicines because Mayzent can also slow the heart rate during the first few days after starting 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 reach the maintenance 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 medicines to avoid an increased effect on the immune system
• vaccines. If you need a vaccination, consult your doctor first. During treatment with Mayzent and for 4 weeks after stopping treatment, you must not receive certain types of vaccines (called live attenuated vaccines) as they may cause the infection they are meant to prevent (see section 2)
• strong inhibitors of CYP2C9 are expected to increase Mayzent levels in the blood and are not recommended to be taken together with Mayzent. Your doctor will advise you accordingly
• carbamazepine and other medicines may lower Mayzent levels in the blood and thus may prevent it from working properly. Your doctor will advise you accordingly
• modafinil and other medicines may lower Mayzent levels in the blood in certain patients and thus may prevent it from working properly. If this applies to you, your doctor will advise you accordingly
• UV phototherapy or PUVA photochemotherapy. UV therapy during Mayzent treatment may increase your risk of developing skin cancer.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Do not use Mayzent during pregnancy, if you are planning a pregnancy, or if you are a woman of childbearing age and not using effective contraception. If Mayzent is used during pregnancy, there is a risk of harm to the unborn baby. If you are a woman of childbearing age, your doctor will inform you of these risks before starting Mayzent treatment and will ask you to take a pregnancy test to confirm you are not pregnant. While taking Mayzent and for at least 10 days after stopping treatment, you must use effective contraception to avoid pregnancy. Discuss reliable contraceptive methods with your doctor.
If you become pregnant while taking Mayzent, inform your doctor immediately. Your doctor will decide to stop treatment (see “If you stop taking Mayzent” in section 3). Appropriate prenatal monitoring will be carried out.
You must not breastfeed during treatment with Mayzent. Mayzent may pass into breast milk and there is a risk of serious adverse effects in the breastfed infant.

Driving and using machines
Your doctor will advise you whether your condition allows you to drive or operate machinery safely.
Mayzent is not expected to affect your ability to drive or use machines when you are on the maintenance dose. However, at the beginning of treatment, you may occasionally feel dizzy. Therefore, on the first day of treatment with Mayzent, you must not drive or operate machinery.

Mayzent contains lactose and soy lecithin
If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
If you are allergic to peanuts or soy, do not use this medicine.

3. How to take Mayzent

Treatment with Mayzent will be supervised by a doctor experienced in the treatment of MS.
Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.

How much Mayzent to take

Starting treatment
You will be given a titration pack, with which the dose will be gradually increased over 5 days. Follow the instructions on the pack (see also the table “Titration pack”).
The purpose of the titration phase is to reduce the risk of heart-related side effects at the beginning of treatment. If there is a risk that your heart rate may become slower or irregular, your doctor may monitor you closely at the start of treatment.

Titration pack

| Day | Dose | Number of Mayzent 0.25 mg tablets to take | |---------|----------|-----------------------------------------------| | Day 1 | 0.25 mg | 1 tablet | | Day 2 | 0.25 mg | 1 tablet | | Day 3 | 0.5 mg | 2 tablets | | Day 4 | 0.75 mg | 3 tablets | | Day 5 | 1.25 mg | 5 tablets |

On day 6, you will switch to the normal maintenance dose of treatment.
During the first 6 days of treatment, it is recommended to take the tablets in the morning, with or without food.

Maintenance dose
The recommended dose is 2 mg once daily (one 2 mg Mayzent tablet), with or without food.
Your doctor may advise you to take only 1 mg once daily (one 1 mg Mayzent tablet or four 0.25 mg Mayzent tablets) if blood tests performed before starting treatment show that your body metabolizes Mayzent slowly (see “Tests before and during treatment”). If this applies to you, please note that you may still safely take five 0.25 mg tablets on day 5 of the titration period, as indicated above.

Mayzent is a medicine for oral use. Swallow the tablet with water.

If you take more Mayzent than you should
If you have taken too many Mayzent tablets or accidentally took the first tablet from the maintenance dose pack instead of the titration pack, inform your doctor immediately. Your doctor may decide to monitor you closely.

If you forget to take Mayzent
If during the first 6 days of treatment you forget to take a dose, inform your doctor before taking the next dose. Your doctor will need to prescribe a new titration pack, and you will have to restart treatment from day 1.

If you forget to take a dose during the maintenance phase (from day 7 onwards), take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue as usual. Do not take a double dose to make up for a missed dose.
If you have forgotten to take Mayzent for 4 or more consecutive days, inform your doctor before taking the next dose. Your doctor will prescribe a new titration pack, and you will have to restart treatment from day 1.

If you stop taking Mayzent
Do not stop taking Mayzent or change the dose without first consulting your doctor.
Mayzent will remain in your body for up to 10 days after stopping treatment. The number of white blood cells (lymphocytes) may remain low for up to 3–4 weeks after stopping Mayzent treatment. The side effects described in this leaflet may still occur during this period (see section 4 “Possible side effects”).

If you need to restart Mayzent after an interruption of more than 4 days, your doctor will prescribe a new titration pack, and you will have to restart treatment from day 1.

Inform your doctor immediately if you feel that your MS worsens after stopping Mayzent treatment.

If you have any doubts about how to use this medicine, consult 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 people)

• Rash with small fluid-filled blisters appearing on red skin (symptoms of a viral infection called herpes zoster, which can be severe)
• A type of skin cancer called basal cell carcinoma (basal cell carcinoma, BCC), which often appears as a pearly nodule but may also take other forms.
• Fever, sore throat and/or mouth ulcers due to infection (lymphopenia)
• Seizures, epileptic attacks
• Vision problems such as shadows or blind spots in the center of vision, blurred vision, difficulty distinguishing colors or details (symptoms of macular edema, which is swelling in the macular area of the retina at the back of the eye)
• Irregular heartbeat (atrioventricular block)
• Slow heartbeat (bradycardia)

Uncommon (may affect up to 1 in 100 people)

• A type of skin cancer called squamous cell carcinoma, which may appear as a solid red nodule, a sore with a crust, or a new sore on an existing scar
• A type of skin cancer called malignant melanoma, which usually develops from an unusual mole. Possible signs of melanoma include moles that may change in size, shape, thickness, or color over time, or the appearance of new moles. Moles may itch, bleed, or ulcerate.

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

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

Not known (frequency cannot be estimated from the available data)

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

If you experience any of these side effects, contact your doctor immediately.
Other side effects
Other side effects include those listed below. If any of these side effects become severe, contact your doctor or pharmacist.
Very common (may affect more than 1 in 10 people)

• Headache
• High blood pressure (hypertension), sometimes with symptoms such as headache and dizziness
• Blood tests showing increased levels of liver enzymes

Common (may affect up to 1 in 10 people)

• New moles
• Dizziness
• Involuntary shaking of the body (tremor)
• Diarrhea
• Malaise (nausea)
• Pain in hands or feet
• Swelling of hands, ankles, legs, or feet (peripheral edema)
• Weakness (asthenia)
• Lung function test results showing reduced lung function

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mayzent

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton/blister pack after "Exp.".
The expiry date refers to the last day of that month.
Do not store above 25 °C.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mayzent contains

• The active substance is siponimod.

Mayzent 0.25 mg film-coated tablets

• Each tablet contains 0.25 mg of siponimod (as siponimod fumaric acid).
• The other components are: Tablet core: monohydrate lactose (see section 2 “Mayzent contains lactose and soy lecithin”), 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 section 2 “Mayzent contains lactose and soy lecithin”), xanthan gum.

Mayzent 1 mg film-coated tablets

• Each tablet contains 1 mg of siponimod (as siponimod fumaric acid).
• The other components are: Tablet core: monohydrate lactose (see section 2 “Mayzent contains lactose and soy lecithin”), 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 section 2 “Mayzent contains lactose and soy lecithin”), xanthan gum.

Mayzent 2 mg film-coated tablets

• Each tablet contains 2 mg of siponimod (as siponimod fumaric acid).
• The other components are: Tablet core: monohydrate lactose (see section 2 “Mayzent contains lactose and soy lecithin”), 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 section 2 “Mayzent contains lactose and soy lecithin”), xanthan gum.

Description of the appearance of Mayzent and the contents of the pack
Mayzent 0.25 mg film-coated tablets are pale red, round tablets with the company logo imprinted on one side and “T” on the other.
Mayzent 1 mg film-coated tablets are violet-white, round tablets with the company logo imprinted on one side and “L” on the other.
Mayzent 2 mg film-coated tablets are pale yellow, round tablets with the company logo imprinted on one side and “II” on the other.
Mayzent 0.25 mg film-coated tablets are available in the following pack sizes:

• titration pack in a wallet container 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.
Not all pack 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 Nuremberg
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50
България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11
Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00
Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf.: +45 39 16 84 00 Tel: +356 2122 2872
Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111
Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00
Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570
España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888
France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600
Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01
Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50
Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439
Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200
Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00
Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

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