ZEPOSIA 0.23 mg / 0.46 mg HARD CAPSULES

2. What you need to know before you take Zeposia

Do not take Zeposia:

• if you are allergic to ozanimod or any of the other ingredients of this medicine (listed in section 6);
• 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 6 months
• if you have certain types of irregular heartbeat or abnormal heart rhythm (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 breastfeeding or think you may be pregnant or are planning to have a baby.

Warnings and precautions

Tell your doctor or pharmacist before you start taking Zeposia if:

• you have a slow heart rate or are taking or have recently taken medicines that slow the heart rate (such as beta-blockers or calcium channel blockers)
• you have severe respiratory problems when sleeping (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 not sure if you have had, chickenpox
• you have recently received or are scheduled to receive a vaccine
• you or others notice a worsening of your 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. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) can cause your disease to worsen, 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 disease 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).

Before you start taking Zeposia, your doctor will perform an electrocardiogram (ECG) to check your heart.

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

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

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

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

While taking Zeposia (and for up to 3 months after stopping it), you may be more prone to infections. Any infection you already have may worsen. Tell your doctor if you get an infection.

During treatment with Zeposia, if you experience vision changes, progressive weakness, clumsiness, memory loss, or confusion, or if you have MS and think your disease is getting worse, talk to 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 a severe headache, confusion, or seizures (epileptic fits) and loss of vision, tell your doctor immediately. These symptoms may be due to a syndrome called posterior reversible encephalopathy syndrome (PRES).

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

Women of childbearing potential

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

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

Worsening of MS after stopping Zeposia

Tell your doctor immediately if you think your MS is getting worse after stopping Zeposia (see “If you stop taking Zeposia” in section 3).

Children and adolescents

Do not give this medicine to children or adolescents under 18 years of age. This is because Zeposia has not been studied in children or adolescents.

Other medicines and Zeposia

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because Zeposia may affect the way other medicines work. Similarly, some medicines may affect the way Zeposia works.

In particular, before taking Zeposia, tell your doctor or pharmacist if you are taking or have recently taken any of the following medicines:

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

Pregnancy and breastfeeding

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

Pregnancy

Do not take Zeposia during pregnancy, if you are trying to become pregnant, or if you are a woman of childbearing potential and not using any effective contraceptive method. If Zeposia is used during pregnancy, it may harm the fetus. If you are a woman of childbearing potential, your doctor will inform you about the risks before starting treatment with Zeposia and ask you to have a pregnancy test to make sure you are not pregnant. You must use an effective contraceptive method while taking Zeposia and for at least 3 months after stopping it. Ask your doctor about reliable contraceptive methods.

Your doctor will give you a card explaining why you should not become pregnant while taking Zeposia.

If you become pregnant while taking Zeposia, tell your doctor immediately. Your doctor will decide whether to stop treatment (see “If you stop taking Zeposia” in section 3). Specialized prenatal monitoring will be performed.

Breastfeeding

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

Driving and using machines

Zeposia has no or negligible influence on the ability to drive and use machines.

Zeposia contains sodium

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

Zeposia contains potassium

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

3. How to take Zeposia

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, ask your doctor or pharmacist again.

How much to take

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

• You will receive a “starter pack” to help you start treatment this way. It contains:

• 4 light gray capsules containing 0.23 mg of ozanimod. You will take one of these capsules on days 1 to 4 of treatment.
• 3 light gray and orange capsules containing 0.46 mg of ozanimod. You will take one of these capsules on days 5, 6, and 7.

• From day 8 onwards, once you have finished the “starter pack”, you will continue with the orange capsules containing the recommended dose of 0.92 mg of ozanimod from the “maintenance pack”. You will continue regular treatment with one 0.92 mg capsule per day. If you have mild or moderate chronic liver problems, your doctor may need to reduce your maintenance dose to one 0.92 mg capsule every other day.

How to take Zeposia

• Zeposia is taken orally.
• Swallow the capsule whole.
• 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, talk to a doctor or go to a hospital immediately. Take the medicine pack and this leaflet with you.

If you forget to take Zeposia

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

If you stop taking Zeposia

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

• for 1 day or more in the first 14 days of treatment
• for more than 7 consecutive days between day 15 and day 28 of treatment
• for more than 14 consecutive days after day 28 of treatment.

You will need to start again with the “starter pack”.

Zeposia will remain in your body for up to 3 months after stopping it. The white blood cell count (lymphocyte count) may also remain low during this time, and you may still experience the side effects described in this leaflet (see section 2 and “Possible side effects” in section 4).

Tell your doctor immediately if you think your MS is getting worse after stopping Zeposia.

If you have any further questions on 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

Tell your doctor or pharmacist immediately if you notice any of the following serious side effects:

• Common:may affect up to 1 in 10 people

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

• Uncommon:may affect up to 1 in 100 people

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

• Rare:may affect up to 1 in 1,000 people

• a brain infection called progressive multifocal leukoencephalopathy (PML) (see section 2).
• liver damage

Other side effects

Tell your doctor or pharmacist if you notice any of the following side effects:

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

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

• Common:may affect up to 1 in 10 people

• throat inflammation (pharyngitis)
• viral respiratory infection (sign of lung infection)
• shingles (herpes zoster)
• cold sores or fever blisters (herpes simplex)
• headache
• low blood pressure
• swelling, especially of ankles and feet, due to fluid retention (peripheral edema)
• increased liver enzyme or bilirubin levels in blood tests (a sign of liver problems) or yellowing of the skin, mucous membranes, and eyes, hyperbilirubinemia, or high bilirubin levels in the blood (jaundice)
• pulmonary abnormalities that can cause shortness of breath.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zeposia

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the blister and carton 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 any damage or signs of tampering with the pack.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Zeposia Composition

• The active ingredient is ozanimod.

• Zeposia 0.23mg hard capsules

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

• Zeposia 0.46mg hard capsules

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

• Zeposia 0.92mg hard capsules

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

• The other components are

• Capsule content:

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

• Capsule shell:

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

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

Product Appearance and Packaging Contents

• The Zeposia 0.23 mg hard capsule, 14.3 mm in length, has a light gray opaque cap and body, with "OZA" printed on the cap and "0.23 mg" printed on the body in black ink.
• The Zeposia 0.46 mg hard capsule, 14.3 mm in length, has an orange opaque cap and a light gray opaque body, with "OZA" printed on the cap and "0.46 mg" printed on the body in black ink.
• The Zeposia 0.92 mg hard capsule, 14.3 mm in length, has an orange opaque cap and body, with "OZA" printed on the cap and "0.92 mg" printed on the body in black ink.

Package Sizes

• The starter pack is a box 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 Authorization Holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

You can request more information about this medicinal product 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 medicinal product is available on the European Medicines Agency website: 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 at the following internet address: www.zeposia-eu-pil.com.