Label: information for the patient

Zeposia 0.23mghard capsules

Zeposia 0.46mghard capsules

Zeposia 0.92mghard capsules

ozanimod

Read this label carefully before taking this medicine, as it contains important information for you.

• Keep this label, 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 side effects, consult your doctor or pharmacist, even if they are not listed in this label. See section4.

Zeposia contains the active ingredient ozanimod, which belongs to a group of medications that can reduce the number of circulating white blood cells (lymphocytes) in the body.

Zeposia is indicated for the following diseases:

• Multiple sclerosis
• Ulcerative colitis.

Multiple sclerosis

Zeposia is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease.

• Multiple sclerosis (MS) is a disease in which the immune system (the body's defenses, including white blood cells) mistakenly attacks the protective sheath that surrounds the nerves in the brain and spinal cord. This prevents the nerves from functioning properly and can produce symptoms such as numbness, difficulty walking, and vision and balance problems.
• Relapsing-remitting multiple sclerosis is characterized by attacks on nerve cells followed by periods of recovery. Symptoms may disappear during periods of recovery, although some may remain.

Zeposia helps combat attacks on nerves by preventing certain white blood cells from reaching the brain and spinal cord, where they could cause inflammation and damage to the protective sheath of nerves.

Ulcerative colitis

Zeposia is indicated for the treatment of adult patients with active moderate to severe ulcerative colitis (UC).

• Ulcerative colitis is an inflammatory bowel disease. If you have ulcerative colitis, other medications will be administered first. If you do not respond sufficiently or are intolerant to these medications, Zeposia may be administered to reduce the signs and symptoms of your disease.

Zeposia helps reduce inflammation in ulcerative colitis by preventing certain white blood cells from reaching the intestinal lining.

Do not take Zeposia:

• if you are allergic to ozanimod or any of the other ingredients in this medicine (listed in section6);
• if your healthcare professional has told you that your immune system is severely weakened
• if you have had a heart attack, angina, stroke, or transient ischemic attack (TIA) or certain types of severe heart failure in the last 6months
• if you have certain types of irregular or abnormal heart rhythms (arrhythmia); your doctor will check your heart before starting treatment
• if you have a severe infection such as hepatitis or tuberculosis
• if you have cancer
• if you have severe liver problems
• if you are pregnant or may become pregnant and are not using an effective contraceptive method.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Zeposia if:

• you have a slow heart rate or are taking or have recently taken medications that slow down your heart rate (such as beta-blockers or calcium channel blockers)
• you have severe sleep apnea without treatment
• you have liver problems
• you have an infection
• you have low levels of a type of white blood cell called lymphocytes
• you have never had or are unsure if you have had chickenpox
• you have recently received or plan to receive a vaccine
• you or others observe an worsening of MS symptoms, as well as any new or unusual symptoms. These symptoms may be due to a rare brain infection called progressive multifocal leukoencephalopathy (PML). If PML is confirmed, your doctor will stop treatment with Zeposia. However, some people may experience a reaction when stopping Zeposia (known as SIRI or immune reconstitution inflammatory syndrome). This reaction can make your disease worse, including worsening of brain function
• you have ever had vision problems or other symptoms of fluid accumulation in the central part of the retina called the macula (a condition called macular edema)
• you have eye inflammation (uveitis)
• you have diabetes (which can cause eye problems)
• you have severe lung disease (pulmonary fibrosis or chronic obstructive pulmonary disease).

Your doctor will perform an electrocardiogram (ECG) before starting treatment to check your heart.

If you have certain heart conditions, your doctor will monitor you for at least the first 6hours after the first dose.

Since Zeposia can increase blood pressure, your doctor may want to monitor your blood pressure periodically.

During treatment with Zeposia, if you experience unexplained nausea, vomiting, abdominal pain on the right side, fatigue, loss of appetite, yellowing of the skin or eyes (jaundice), and/or dark urine, inform your doctor immediately. These symptoms may be due to liver problems.

Your doctor will request blood tests to monitor liver function before, during, and after treatment. If the test results indicate liver problems, you may need to stop treatment with Zeposia.

While taking Zeposia (and for up to 3months after stopping it), you may be more susceptible to infections. Any existing infection may worsen. Consult your doctor if you develop an infection.

During treatment with Zeposia, if you experience vision changes, progressive weakness, clumsiness, memory loss, or confusion, or if you have MS and believe your disease is worsening progressively, speak with your doctor immediately. These symptoms may be due to PML, a rare brain infection that can cause severe disability or death.

During treatment with Zeposia, if you experience severe headache, confusion, or seizures (epileptic crises) and vision loss, consult your doctor immediately. These symptoms may be due to a condition called posterior reversible encephalopathy syndrome (PRES).

Since Zeposia can increase the risk of skin cancer, you should limit your exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and applying sunscreen regularly (with a high sun protection factor).

Pregnant women with the possibility of becoming pregnant

If used during pregnancy, Zeposia may harm the fetus. Before starting treatment with Zeposia, your doctor will inform you of the risks and ask you to take a pregnancy test to ensure you are not pregnant. Your doctor will give you a card explaining why you should not become pregnant while taking Zeposia. They will also tell you what to do to avoid becoming pregnant while taking Zeposia. You must use an effective contraceptive method during treatment and for at least 3months after stopping treatment (see section“Pregnancy and breastfeeding”).

If any of these points apply to you, inform your doctor or pharmacist before taking Zeposia.

Worsening of MS after stopping Zeposia treatment

Inform your doctor immediately if you believe your MS is worsening after stopping treatment with Zeposia (see “If you stop treatment with Zeposia” in section3).

Children and adolescents

Do not administer this medication to children or adolescents under 18years old. This is because Zeposia has not been studied in children or adolescents.

Other medications and Zeposia

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This is because Zeposia may affect how other medications work. Similarly, some medications may affect how Zeposia works.

Particularly, before taking Zeposia, inform your doctor or pharmacist if you are taking or have taken recently any of the following medications:

• medications that inhibit or modulate the immune system (e.g., cyclosporine)
• medications used to treat MS, such as alemtuzumab, interferon beta, dimethyl fumarate, glatiramer acetate, mitoxantrone, natalizumab, or teriflunomide
• medications used to treat ulcerative colitis, such as azathioprine and 6‑mercaptopurine
• gemfibrozil to reduce blood lipid or cholesterol levels
• clopidogrel, a medication used to prevent blood clots
• rifampicin, an antibiotic used to treat tuberculosis and other severe infections
• medications called monoamine oxidase inhibitors to treat depression (e.g., phenelzine) or Parkinson's disease (e.g., selegiline)
• medications that slow down heart rate (such as beta-blockers or calcium channel blockers)
• certain types of live vaccines. Live attenuated vaccines should be avoided during treatment and for 3months after treatment.

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, or may become pregnant, consult your doctor before using this medication.

Pregnancy

Do not use Zeposia during pregnancy, if you are trying to become pregnant, or if you are a woman with the possibility of becoming pregnant and are not using an effective contraceptive method. If Zeposia is used during pregnancy, there is a risk of harming the fetus. Before starting treatment with Zeposia, your doctor will inform you of the risks and ask you to take a pregnancy test to ensure you are not pregnant. Your doctor will give you a card explaining why you should not become pregnant while taking Zeposia. They will also tell you what to do to avoid becoming pregnant while taking Zeposia. You must use an effective contraceptive method during treatment and for at least 3months after stopping treatment (see section“Pregnancy and breastfeeding”).

If you become pregnant while taking Zeposia, inform your doctor immediately. Your doctor will decide to stop treatment (see “If you stop treatment with Zeposia” in section3). A specialized prenatal check-up will be performed.

Breastfeeding

You should not breastfeed while taking Zeposia. Zeposia may pass into breast milk and there is a risk of severe side effects for the baby.

Driving and operating machinery

The influence of Zeposia on the ability to drive and operate machinery is negligible or insignificant.

Zeposia contains sodium

This medication contains less than 1mmol of sodium (23mg) per capsule; it is essentially “sodium-free”.

Zeposia contains potassium

This medication contains less than 1mmol of potassium (39mg) per capsule; it is essentially “potassium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

How much to take

When starting Zeposia for the first time, you need to take a low dose and gradually increase it to reduce any effect that slows down your heart rate.

• You will receive a “starting treatment package” to help you start treatment in this way. It contains:

• 4light gray capsules containing 0.23mg of ozanimod. You will take one of these capsules on days1 to4 of treatment.
• 3light gray and orange capsules containing 0.46mg of ozanimod. You will take one of these capsules on days5, 6, and7.

• From day8, once you have finished the “starting treatment package”, you will continue with the orange capsules containing the recommended dose of 0.92mg of ozanimod from the “maintenance package”. You will continue regular treatment with a daily capsule of 0.92mg. If you have mild or moderate chronic liver disease, your doctor may have to reduce your “maintenance” dose to a capsule of 0.92mg every other day.

How to take Zeposia

• Zeposia is taken orally.
• Take the entire capsule.
• You can take the capsule with or without food.

If you take more Zeposia than you should

If you take more Zeposia than you should, consult a doctor or go to the hospital immediately. Bring the medication package and this leaflet with you.

If you forget to take Zeposia

• If you forget one or more doses in the first 14days after starting Zeposia, consult your doctor about how to restart treatment.
• If you forget a dose of Zeposia after the first 14days after starting Zeposia, take it as soon as you remember. However, if you forget the dose for an entire day, skip the missed dose and take the next dose at the usual time.
• Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Zeposia

• Do not stop taking Zeposia without consulting your doctor first.
• Consult your doctor about how to restart treatment if you have stopped taking Zeposia:

• for 1day or more in the first 14days of treatment
• for more than 7consecutive days between day15 and day28 of treatment
• for more than 14consecutive days after day28 of treatment.

You will have to start again with the “starting treatment package”.

Zeposia will remain in your body for a maximum of 3months after stopping it. Your white blood cell count (lymphocyte count) may also remain low during this time and the side effects described in this leaflet (see section2 and“Possible side effects”in section4) may still occur.

Inform your doctor immediately if you think your MS has worsened after stopping treatment with Zeposia.

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

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

Severe side effects

Inform your doctor or pharmacist immediately if you observe any of the severe side effects mentioned below:

• Frequent:can affect up to 1 in 10people

• low heart rate
• urinary tract infection
• high blood pressure.

• Uncommon:can affect up to 1 in 100people

• allergic reaction, symptoms may include a rash
• blurred vision (macular edema).

• Rare:can affect up to 1 in 1000people

• brain infection called progressive multifocal leukoencephalopathy (PML) (see section2).
• liver damage

Other side effects

Inform your doctor or pharmacist if you observe any of the following side effects:

• Very common:can affect more than 1 in 10people

• infections of the nose or nasal passages, the nasal cavity, the mouth, the throat (pharynx) or the larynx caused by viruses
• low levels of a type of white blood cell called lymphocytes.

• Frequent:can affect up to 1 in 10people

• throat inflammation (pharyngitis)
• respiratory infection caused by a virus (sign of pulmonary infection)
• shingles (herpes zoster)
• simple herpes or mouth sores (herpes labial)
• headache
• low blood pressure
• swelling, especially of ankles and feet, due to fluid retention (peripheral edema)
• increased levels of liver enzymes or bilirubin in blood tests (a sign of liver problems) or yellow pigmentation in the skin, mucosa, and eyes, hyperbilirubinemia or high levels of bilirubin in blood (jaundice)
• pulmonary anomalies that can cause shortness of breath.

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 prospectus. You can also report them directly through thenational notification system included in theAppendixV. By 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 blister pack and on the box after “CAD”/“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 any damage or signs of improper handling on the packaging.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Zeposia

• The active ingredient is ozanimod.

• Zeposia 0.23 mg hard capsules

Each hard capsule contains 0.23 mg of ozanimod (as hydrochloride).

• Zeposia 0.46 mg hard capsules

Each hard capsule contains 0.46 mg of ozanimod (as hydrochloride).

• Zeposia 0.92 mg hard capsules

Each hard capsule contains 0.92 mg of ozanimod (as hydrochloride).

• The other components are

• Hard capsule content:

Microcrystalline cellulose, anhydrous colloidal silica, sodium croscarmellose and magnesium stearate.

• Hard capsule coating:

• Each 0.23 mg hard capsule contains gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide black (E172) and iron oxide red (E172).
• Each 0.46 mg hard capsule contains gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide black (E172) and iron oxide red (E172).
• Each 0.92 mg hard capsule contains gelatin, titanium dioxide (E171), iron oxide yellow (E172) and iron oxide red (E172).

• Printing ink:iron oxide black (E172), shellac (E904), polypropylene glycol (E1520), concentrated ammonia solution (E527) and potassium hydroxide (E525).

Appearance of the product and contents of the pack

• The 14.3 mm hard capsule of Zeposia 0.23 mg has a light grey opaque cap and body, with the inscription “OZA” on the cap and “0.23 mg” on the body in black ink.
• The 14.3 mm hard capsule of Zeposia 0.46 mg has a light grey opaque body and an orange opaque cap, with the inscription “OZA” on the cap and “0.46 mg” on the body in black ink.
• The 14.3 mm hard capsule of Zeposia 0.92 mg has an orange opaque cap and body, with the inscription “OZA” on the cap and “0.92 mg” on the body in black ink.

Pack sizes

• The starting treatment pack is a blister pack containing 7 hard capsules: 4 hard capsules of 0.23 mg and 3 hard capsules of 0.46 mg.
• The maintenance pack contains 28 hard capsules of 0.92 mg or 98 hard capsules of 0.92 mg.

Only some pack sizes may be marketed.

Marketing authorisation holder

Bristol-Myers Squibb Pharma EEIG

254 Plaza

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

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

Last update of the summary of product characteristics

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/.

You can access detailed information about this medicinal product by scanning the QR code included in the outer packaging with your smartphone. You can also access this information on the following website:www.zeposia-eu-pil.com.