ZEPOSIA 0.23 MG/0.46 MG Kapsułki twarde

Treść ulotki

1. Zeposia 0.23 mg hard capsules, 0.46 mg hard capsules, 0.92 mg hard capsules
   1. What is Zeposia and what is it used for
   2. What you need to know before you take Zeposia
   3. How to take Zeposia
   4. Possible side effects
   5. How to store Zeposia
   6. Package contents and other information

Zeposia 0.23 mg hard capsules, 0.46 mg hard capsules, 0.92 mg hard capsules

ozanimod

Read 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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Zeposia and what is it used for

Zeposia contains the active ingredient ozanimod, belonging to a group of medicines that can
reduce the number of white blood cells (lymphocytes) circulating freely 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 coating surrounding nerve fibers in the brain and spinal cord. This prevents nerve fibers from functioning properly and can cause symptoms such as numbness, difficulty walking, and problems with vision and balance.
• In relapsing-remitting multiple sclerosis, attacks on nerve cells are followed by periods of recovery. Symptoms may disappear during recovery periods, but some problems may persist.

Zeposia helps to protect against attacks that affect nerve fibers by preventing certain
white blood cells from reaching the brain and spinal cord, where they could cause inflammation
and damage to the protective coating of nerves.
Ulcerative Colitis
Zeposia is indicated for the treatment of adult patients with ulcerative colitis (UC) in an active phase of moderate
to severe degree.

• Ulcerative colitis is an inflammatory bowel disease. If you have ulcerative colitis, you will first be treated with other medicines. If you do not respond adequately or if you are

intolerant to these medicines, you may be given Zeposia to reduce the signs and
symptoms of the disease.
Zeposia helps to reduce inflammation in ulcerative colitis by preventing certain white blood cells
from reaching the inner lining of the intestine.

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 provider has told you that your immune system is severely weakened;
• if you have had a heart attack, angina, stroke or mini-stroke (transient ischaemic attack, TIA) in the last 6 months, or certain types of severe heart failure;
• if you have certain types of irregular or abnormal heartbeats (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 are a woman of childbearing potential who is not using effective contraception.

Warnings and precautions
Talk to your doctor or pharmacist before taking Zeposia if:

• you have a slowed heartbeat or are taking or have recently taken medicines that slow the heartbeat (such as beta-blockers or calcium channel blockers);
• you have untreated severe sleep breathing problems (severe sleep apnea);
• you have liver problems;
• you have an infection;
• you have low levels of a type of white blood cells 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 a worsening of MS symptoms as well as new or unusual symptoms. These 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 develop a reaction when Zeposia is stopped. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) can lead to a worsening of your condition, including a worsening of brain function;
• you have ever had problems with your vision or other symptoms of fluid build-up 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 a severe lung disease (pulmonary fibrosis or chronic obstructive pulmonary disease).

Before starting treatment with Zeposia, your doctor will check your heart using an
electrocardiogram (ECG).
If you suffer from certain heart conditions, your doctor will monitor you for at least the first 6 hours
after the first dose.
Because Zeposia can raise blood pressure, your doctor may need to check
your blood pressure regularly.
During treatment with Zeposia, if you experience unexplained nausea, vomiting, pain in the upper right
part of your abdomen (abdominal pain), fatigue, loss of appetite, yellowing of the
skin or the whites of your eyes (jaundice) and/or dark urine, consult your doctor immediately.
These symptoms may be caused by a liver problem.
Before, during and after treatment, your doctor will ask you to have blood tests to
monitor liver function. If the test results indicate a liver problem, you may
need to stop treatment with Zeposia.
During treatment with Zeposia, you may
develop infections more easily (and for a period of up to 3 months after stopping it). An existing infection may worsen. Talk to your doctor if
you develop an infection.
During treatment with Zeposia, if you develop vision disturbances, progressive weakness,
clumsiness, memory loss or confusion, or if you have MS and think your condition is
progressively worsening, talk to your doctor immediately. These symptoms could
be caused by PML, a rare brain infection that can lead to severe disability or death.
If you experience a severe headache, feel confused or
have seizures (fits) and loss of vision during treatment with Zeposia, consult your doctor immediately. These symptoms
may be due to a syndrome called reversible posterior encephalopathy syndrome
(PRES).
Since Zeposia can increase the risk of skin cancer, you should limit exposure to sunlight and UV (ultraviolet) light, wearing protective clothing and applying regular
sunscreen (with a high protection factor).
Women of childbearing potential
If used during pregnancy, Zeposia can cause harm to the unborn child. Before starting
treatment with Zeposia, your doctor will explain the risks to you 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 during treatment with Zeposia. This card also explains
what to do to avoid pregnancy during treatment with Zeposia. You must use effective
contraception during treatment and for 3 months after stopping it (see section
“ Pregnancy and breastfeeding”).
If you fall into any of the above categories, talk to your doctor or pharmacist before taking Zeposia.

Worsening of MS after stopping treatment with Zeposia
Tell your doctor immediately if you think there is a worsening of MS after stopping
treatment with Zeposia (see “ If you stop taking Zeposia” in section 3).

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age, 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 other medicines work and other
medicines can affect the way Zeposia works.
In particular, tell your doctor or pharmacist before taking Zeposia if you are taking or have
recently taken any of the following medicines:

• medicines that suppress or modulate the immune system (e.g. ciclosporin)
• 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 reduce fat or cholesterol levels in the blood;
• clopidogrel, a medicine used to prevent blood clots;
• rifampicin, an antibiotic used to treat tuberculosis and other serious infections
• medicines called monoamine oxidase inhibitors for the treatment of 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 for 3 months afterwards.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant or are breastfeeding,
ask your doctor for advice before taking this medicine.
Pregnancy
Do not use Zeposia during pregnancy, if you intend to become pregnant or if you are a woman of childbearing
potential who is not using effective contraception. If Zeposia is used during pregnancy, there is a
risk of harm to the unborn child. If you are a woman of childbearing potential, your doctor will inform you of this risk
before starting treatment with Zeposia and will ask you to have a pregnancy test to
make sure you are not pregnant. You must use effective contraception during treatment with
Zeposia and for at least 3 months after stopping it. Ask your doctor for information about reliable
contraceptive measures.
Your doctor will give you a card explaining why you should not become pregnant during
treatment with Zeposia.
If you become pregnant during treatment with Zeposia, tell your doctor immediately. The doctor
will decide to stop treatment (see “If you stop taking Zeposia”in
section 3). Specialist prenatal monitoring will be performed.
Breastfeeding
Do not breastfeed during treatment with Zeposia. Zeposia can pass into breast milk
and there is a risk of serious side effects for the baby.

Driving and using machines
Zeposia does not affect, or has a negligible effect on, the ability to drive and operate machines.

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

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

3. How to take Zeposia

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your
doctor or pharmacist.

Dosage to be taken
When you start taking Zeposia, you must take a low dose and increase it gradually in order to
reduce any potential effect of slowing down the heart rate.

• You will be provided with a “treatment starter pack” to help you start treatment in this way. The pack contains: o 4 light grey capsules containing 0.23 mg of ozanimod. You must take one of these capsules on days 1 to 4 of treatment; o 3 light grey and orange capsules containing 0.46 mg of ozanimod. You must take one of these capsules on days 5, 6 and 7.
• On day 8 and thereafter, once you have completed the “treatment starter pack”, you will switch to a “maintenance pack” with orange capsules each containing the recommended dose of 0.92 mg of ozanimod. 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 the “maintenance” dose to one 0.92 mg capsule on alternate days.

How to take Zeposia

• Zeposia is for oral use.
• 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, consult your doctor or go to hospital immediately.

If you forget to take Zeposia

• If you forget one or more doses during the first 14 days of treatment with Zeposia, consult your doctor for instructions on resuming treatment.
• If you forget a dose of Zeposia after the first 14 days of treatment with 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 the usual time.
• Do not take a double dose to make up for a missed dose.

If you stop taking Zeposia

• Do not stop treatment with Zeposia without consulting your doctor first.
• Consult your doctor about resuming 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 starter pack” again.

Zeposia remains in the body for a period of up to 3 months after stopping treatment. The
number of white blood cells in the blood (lymphocyte count) may remain low even during this
paragraph 2 and “Possible side effects”in paragraph 4).
Immediately inform your doctor if you think there is a worsening of MS after stopping
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
• low heart rate
• urinary tract infection
• increased blood pressure
• uncommon:may affect up to 1 in 100 people
• allergic reaction, the signs of which may include a skin rash
• blurred vision (macular edema)
• rare:may affect up to 1 in 1,000 people
• 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
• infections of the nose or nostrils, nasal cavity, mouth, throat (pharynx) or larynx, caused by viruses
• low level of a type of white blood cells called lymphocytes
• common:may affect up to 1 in 10 people
• inflammation of the throat (pharyngitis)
• respiratory infection caused by a virus (sign of infection in the lungs)
• herpes zoster (shingles)
• herpes simplex or cold sores (oral herpes)
• headache
• low blood pressure
• swelling, especially in the 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 yellowing of the skin, mucous membranes or eyes hyperbilirubinemia or high levels of bilirubin in the blood (jaundice)
• lung abnormalities that can cause shortness of breath

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 through 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 the package after “Scad.”/“EXP”. The expiry date refers to the last day of that month.
• Do not store at a temperature above 25°C.
• Do not use this medicine if you notice signs of damage or tampering of the packaging.
• Do not dispose of any medicine in 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 Zeposia contains

• The active ingredient is ozanimod.
• Zeposia 0.23 mg hard capsulesEach hard capsule contains 0.23 mg of ozanimod (as hydrochloride).
• Zeposia 0.46 mg hard capsulesEach hard capsule contains 0.46 mg of ozanimod (as hydrochloride).
• Zeposia 0.92 mg hard capsulesEach hard capsule contains 0.92 mg of ozanimod (as hydrochloride).
• The other ingredients are
• Capsule contents:Microcrystalline cellulose, anhydrous colloidal silicon dioxide, sodium croscarmellose, 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), propylene glycol (E1520), concentrated ammonia solution (E527), potassium hydroxide (E525)

Description of Zeposia and package contents

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

Packs

• The starter pack is a carton containing 7 hard capsules: 4 hard capsules of 0.23 mg and 3 hard capsules of 0.46 mg.
• Maintenance pack containing 28 hard capsules of 0.92 mg or 98 hard capsules of 0.92 mg.

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
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11
[email protected]

Lietuva
Swixx Biopharma UAB
Tel: + 370 52 369140
[email protected]

България
Swixx Biopharma EOOD
Тел.: + 359 2 4942 480
[email protected]

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11
[email protected]

Česká republika
Bristol-Myers Squibb spol. s r.o.
Tel: + 420 221 016 111
[email protected]

Magyarország
Bristol-Myers Squibb Kft.
Tel.: + 36 1 301 9797
[email protected]

Danmark
Bristol-Myers Squibb Denmark
Tlf: + 45 45 93 05 06
[email protected]

Malta
A.M. Mangion Ltd
Tel: + 356 23976333
[email protected]

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA
Tel: 0800 0752002 (+ 49 89 121 42 350)
[email protected]

Nederland
Bristol-Myers Squibb B.V.
Tel: + 31 (0)30 300 2222
[email protected]

Eesti
Swixx Biopharma OÜ
Tel: + 372 640 1030
[email protected]

Norge
Bristol-Myers Squibb Norway AS
Tlf: + 47 67 55 53 50
[email protected]

Ελλάδα
Bristol-Myers Squibb A.E.
Τηλ: + 30 210 6074300
[email protected]

Österreich
Bristol-Myers Squibb GesmbH
Tel: + 43 1 60 14 30
[email protected]

España
Bristol-Myers Squibb, S.A.
Tel: + 34 91 456 53 00
[email protected]

Polska
Bristol-Myers Squibb Polska Sp. z o.o.
Tel.: + 48 22 2606400
[email protected]

France
Bristol-Myers Squibb SAS
Tél: + 33 (0)1 58 83 84 96
[email protected]

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa,
S.A.
Tel: + 351 21 440 70 00
[email protected]

Hrvatska
Swixx Biopharma d.o.o.
Tel: + 385 1 2078 500
[email protected]

România
Bristol-Myers Squibb Marketing Services S.R.L.
Tel: + 40 (0)21 272 16 19
[email protected]

Ireland
Bristol-Myers Squibb Pharmaceuticals uc
Tel: 1 800 749 749 (+ 353 (0)1 483 3625)
[email protected]

Slovenija
Swixx Biopharma d.o.o.
Tel: + 386 1 2355 100
[email protected]

Ísland
Vistor ehf.
Sími: + 354 535 7000
[email protected]

Slovenská republika
Swixx Biopharma s.r.o.
Tel: + 421 2 20833 600
[email protected]

Italia
Bristol-Myers Squibb S.r.l.
Tel: + 39 06 50 39 61
[email protected]

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab
Puh/Tel: + 358 9 251 21 230
[email protected]

Κύπρος
Bristol-Myers Squibb A.E.
Τηλ: 800 92666 (+ 30 210 6074300)
[email protected]

Sverige
Bristol-Myers Squibb Aktiebolag
Tel: + 46 8 704 71 00
[email protected]

Latvija
Swixx Biopharma SIA
Tel: + 371 66164750
[email protected]

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website, https://www.ema.europa.eu/ .
For detailed information on this medicine, also scan the QR code on the outer packaging with a smartphone. The same information is available at:
www.zeposia-eu-pil.com .

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION
Scientific conclusions
In light of the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for ozanimod, the PRAC’s scientific conclusions are as follows:
In light of the available data on immune reconstitution inflammatory syndrome (IRIS) from the literature and in light of a plausible mechanism of action, the PRAC considers that there is at least a reasonable possibility of a causal relationship between ozanimod and IRIS. The PRAC concluded that the product information for products containing ozanimod should be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the overall conclusions and with the justification for the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on ozanimod, the CHMP considers that the benefit-risk ratio of the medicines containing ozanimod is unchanged, save for the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation.