1. What Zeposia is and what it is used for

Zeposia contains the active substance ozanimod that belongs to a group of medicines which can reduce the number of white blood cells (lymphocytes) circulating freely round 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) wrongly attack the protective coat around the nerves in the brain and spinal cord. This stops the nerves from working properly and may result in symptoms such as: numbness, difficulty in walking, and problems with vision and balance.
• In relapsing remitting multiple sclerosis, attacks on the nerve cells are followed by periods of recovery. The symptoms may disappear during the recovery periods, but some problems may remain.

Zeposia helps to protect against attacks on the nerves by stopping certain white blood cells reaching the brain and spine where they could cause inflammation and damage the nerves protective coating.

Ulcerative colitis

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

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

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

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 you have a severely weakened immune system
• if you have had a heart attack, angina, stroke or mini-stroke (Transient Ischaemic Attack – TIA), or certain types of severe heart failure in the last 6 months
• if you have certain types of irregular or abnormal heartbeats (arrhythmia) – your doctor will check your heart before starting treatment
• if you have severe infection such as hepatitis or tuberculosis
• if you have cancer
• if you have severe liver problems
• if you are pregnant or a women of childbearing potential not using effective contraception.

Warnings and precautions

Talk to your doctor or pharmacist before taking Zeposia if:

• you have a slow heart rate or you are taking or have recently taken medicines that slow your heart rate (such as beta blockers or calcium channel blockers);
• you have untreated severe breathing problems when you sleep (severe sleep apnoea);
• you have problems with your liver;
• 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 had or are planning to have a vaccination;
• you or others notice worsening of your MS symptoms as well as any new or unfamiliar symptoms. These may be due to a rare infection of the brain called progressive multifocal leukoencephalopathy (PML). If PML is confirmed, your doctor will stop treatment with Zeposia. However, some people may get a reaction when Zeposia is removed. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) may lead to your condition getting worse, including worsening of brain function;
• you have ever had problems with your vision or other symptoms of build-up of fluid in the central area of the retina called the macula (a condition called macular oedema);
• you have inflammation of the eye (uveitis);
• you have diabetes (which can cause problems with your eyes);
• you have severe lung disease (pulmonary fibrosis or chronic obstructive pulmonary disease);

Before you start taking Zeposia, your doctor will check your heart using an electrocardiogram (ECG).
If you have certain heart conditions your doctor will monitor you for at least the first 6 hours after your first dose.

As Zeposia can increase your blood pressure, your doctor may want to check your blood pressure regularly.

During treatment with Zeposia, if you develop unexplained nausea, vomiting, pain on the right side of the stomach area (abdominal pain), tiredness, loss of appetite, yellowing of your skin or the whites of your eyes (jaundice) and/or dark urine, speak to your doctor straight away. These symptoms may be due to a problem with your liver.

Before, during and after the treatment, your doctor will request blood tests to monitor your liver function. If your test results indicate a problem with your liver you may have to interrupt treatment with Zeposia.

While you are taking Zeposia (and for up to 3 months after you stop taking it), you may get infections more easily. Any infection that you already have may get worse. Talk to your doctor if you develop an infection.

During treatment with Zeposia, if you develop disturbance of vision, progressive weakness, clumsiness, memory loss or confusion, or if you have MS and you think your disease is getting progressively worse, speak to your doctor straight away. These symptoms may be due to PML, a rare brain infection that may lead to severe disability or death.

During treatment with Zeposia, if you develop a severe headache, feel confused, or have seizures (fits) and loss of vision, speak to your doctor straight away. These symptoms may be due to a syndrome called posterior reversible encephalopathy syndrome (PRES).

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

Women of childbearing potential

If used during pregnancy, Zeposia can harm the unborn baby. Before you start treatment with Zeposia, your doctor will explain the risk to you and ask you to do a pregnancy test in order to ensure that you are not pregnant. Your doctor will give you a card which explains why you should not become pregnant while taking Zeposia. It also explains what you should do to avoid becoming pregnant while you are taking Zeposia. You must use effective contraception during treatment and for 3 months after stopping treatment (see section “Pregnancy and breast-feeding”).

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

Worsening of MS after stopping Zeposia treatment

Tell your doctor straight away if you think your MS worsens after you have stopped treatment with Zeposia (see “If you stop taking Zeposia” in section 3).

Children and adolescents

Do not give this medicine to children and adolescents aged under 18 years. This is because Zeposia has not been studied in children and 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 can affect the way some other medicines work. Also some other medicines can 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 which suppress or modulate your immune system (e.g. ciclosporin)
• medicines used to treat MS, such as alemtuzumab, beta interferon, dimethyl fumarate, glatiramer acetate, mitoxantrone, natalizumab or teriflunomide
• medicines used to treat ulcerative colitis, such as azathioprine and 6-mercaptopurine
• gemfibrozil to reduce levels of fats or cholesterol in the blood
• clopidogrel, medicine used to prevent blood clots
• rifampicin, an antibiotic for treating tuberculosis and other serious infections
• medicines called monoamine oxidase inhibitors for treating depression (e.g. phenelzine) or Parkinson’s disease (e.g. selegiline)
• medicines that slow your heart rate (such as beta-blockers or calcium channel blockers)
• certain type of vaccines. Live attenuated vaccines should be avoided during and for 3 months after treatment.

Pregnancy and breast-feeding

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

Pregnancy

Do not use Zeposia during pregnancy, if you are trying to become pregnant or if you are a woman who could become pregnant and you are not using effective contraception. If Zeposia is used during pregnancy, there is a risk of harm to the unborn baby. If you are a woman who could become pregnant, your doctor will inform you about this risk before you start treatment with Zeposia and will ask you to do a pregnancy test in order to ensure that you are not pregnant. You must use effective contraception while taking Zeposia and for at least 3 months after you stop taking it. Ask your doctor about reliable methods of contraception.

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

If you do become pregnant while taking Zeposia, tell your doctor straight away. Your doctor will decide to stop treatment (see “If you stop taking Zeposia” in section 3). Specialised pre‑natal monitoring will be performed.

Breast-feeding

You should not breast-feed while you are taking Zeposia. Zeposia can 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 your ability to drive and use machines.

Zeposia contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium‑free’.

Zeposia contains potassium

This medicine contains less than 1 mmol potassium (39 mg) per capsule, that is to say essentially ‘potassium -free’.

3. How to take Zeposia

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take

When you first start taking Zeposia, you need to take at a low dose and gradually build up, to reduce any effect in slowing your heart rate.

• You will be given a ‘treatment initiation pack’ to help you start treatment in this way. It contains:
  • 4 light-grey capsules, containing 0.23 mg ozanimod. You take one of these on days 1 to 4 of treatment.
  • 3 light-grey and orange capsules, containing 0.46 mg ozanimod. You take one of these on days 5, 6 and 7.
• On day 8 and thereafter, once you have completed the ‘initiation pack’, you will move on to a ‘maintenance pack’ with orange capsules each containing the recommended dose of 0.92 mg ozanimod. You will continue regular treatment with one 0.92 mg capsule daily. 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 for oral use.
• Swallow the capsule whole.
• You can take the capsule either 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 straight away. Take the medicine pack and this leaflet with you.

If you forget to take Zeposia

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

If you stop taking Zeposia

• Do not stop taking Zeposia without talking to your doctor first.
• Talk to your doctor about how to re-start your treatment if you have stopped taking Zeposia:
  • for 1 day or more during 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 the ‘treatment initiation pack’ again.

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

Tell your doctor straight away if you think your MS worsens after you have stopped treatment with 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 serious side effects listed below:

• Common: may affect up to 1 in 10 people
  • slow heart rate
  • urinary tract infection
  • increase in blood pressure
• Uncommon: may affect up to 1 in 100 people
  • allergic reaction – the signs may include a rash.
  • blurred vision (macular oedema)
• Rare: may affect up to 1 in 1,000 people
  • brain infection called progressive multifocal leukoencephalopathy (PML) (see section 2)
  • liver injury

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
  • infections of the nose or nostrils, nasal cavity, mouth, throat (pharynx), or voice box (larynx) caused by viruses
  • low level of a type of white blood cell – called lymphocytes
• Common: may affect up to 1 in 10 people
  • inflammation of the throat (pharyngitis)
  • respiratory infection caused by virus (sign of lungs infection)
  • herpes zoster (shingles)
  • herpes simplex or cold sores (oral herpes)
  • headache
  • drop in blood pressure
  • swelling especially of the ankles and feet, due to fluid retention (peripheral oedema)
  • increased liver enzyme or bilirubin levels in blood tests (a sign of liver problems) or yellow pigmentation of the skin, mucus membrane or eyes hyperbilirubinaemia or high blood levels of bilirubin (jaundice)
  • lung abnormalities which can cause breathlessness

Reporting of side effects

If you get 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. How to store 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.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Zeposia contains

• The active substance 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 ingredients are
  • Capsule content:
    Microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, 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: iron oxide black (E172), Shellac (E904), propylene glycol (E1520), concentrated ammonia solution (E527), potassium hydroxide (E525)

What Zeposia looks like and contents of the pack

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

Pack sizes

• Treatment initiation pack is a wallet pack containing 7 hard capsules: 4 x 0.23 mg hard capsules and 3 x 0.46 mg hard capsules.
• Maintenance pack containing 28 x 0.92 mg hard capsules or 98 x 0.92 mg hard capsules.

Not all pack sizes may be marketed.

Marketing Authorisation 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

This leaflet was last revised in

Other sources of information

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

Detailed information on this medicine is also available by scanning the QR code on the outer packaging with a smartphone. The same information is available on the following URL: www.zeposia-eu-pil.com.