Zeposia 0.23 mg/0.46 mg hard capsules

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Zeposia 0.23 mg hard capsules

Zeposia 0.46 mg hard capsules

Zeposia 0.92 mg hard capsules

ozanimod

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you must not give it to others, even if they have the same symptoms as you, since it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Zeposia is and what it is used for
2. What you need to know before taking 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 Zeposia is and what it is used for

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

Zeposia is indicated for the following conditions:

• 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 defences, including white blood cells) mistakenly attacks the protective covering surrounding the nerves in the brain and spinal cord. This prevents the nerves from functioning properly and may cause symptoms such as numbness, difficulty walking, and vision and balance problems.
• In relapsing-remitting multiple sclerosis, attacks on nerve cells are followed by periods of recovery. Symptoms may disappear during recovery periods, although some may persist.

Zeposia helps to prevent attacks on nerves by blocking certain white blood cells from reaching the brain and spinal cord, where they could cause inflammation and damage the nerves' protective covering.

Ulcerative colitis

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

• Ulcerative colitis is an inflammatory bowel disease. If you have ulcerative colitis, you will first be given other medications. If you do not respond adequately or are intolerant to these medications, Zeposia may be prescribed 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.

2. What you need to know before starting Zeposia

Do not take Zeposia:

• if you are allergic to ozanimod or to 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]) or certain types of severe heart failure within the past 6 months;
• if you have certain types of irregular or abnormal heartbeat (arrhythmia); your doctor will check your heart before starting treatment;
• if you have a serious infection such as hepatitis or tuberculosis;
• if you have cancer;
• if you have severe liver problems;
• if you are pregnant or could become pregnant and are not using an effective contraceptive method.

Warnings and precautions

Talk to your doctor or pharmacist before starting 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 untreated breathing problems during sleep (severe sleep apnoea);
• 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 unsure whether you have had, chickenpox;
• you have recently received or plan to receive a vaccine;
• you or others notice worsening of MS symptoms or 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) may cause your condition to worsen, including worsening of brain function;
• you have ever had vision problems or other symptoms of fluid buildup in the central area 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).

Before starting 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 your first dose.

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

During treatment with Zeposia, if you experience nausea without apparent cause, vomiting, pain in the right side of the abdominal area (abdominal pain), 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 a liver problem.

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

While taking Zeposia (and for a period of up to 3 months after stopping it), you may be more likely to get 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 condition is progressively worsening, 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 a severe headache, confusion, seizures (epileptic fits), or loss of vision, consult your doctor immediately. These symptoms may be due to a condition called reversible posterior encephalopathy syndrome (PRES).

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

Women who could become pregnant

If used during pregnancy, Zeposia may harm the unborn baby. Before starting Zeposia, your doctor will inform you about the risks and will ask you to take a pregnancy test to confirm you are not pregnant. Your doctor will give you a card explaining why you must not become pregnant while taking Zeposia and will advise you on how to avoid pregnancy while on this treatment. You must use an effective contraceptive method during treatment and for 3 months after stopping treatment (see section “Pregnancy and breastfeeding”).

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

Worsening of MS after stopping Zeposia treatment

Inform your doctor immediately if you think your MS is worsening after stopping Zeposia treatment (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 need to take any other medicines. This is because Zeposia may affect how other medicines work. Likewise, some medicines may affect how Zeposia works.

In particular, before taking Zeposia, inform 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, used to reduce levels of fats or cholesterol 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 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 for up to 3 months after treatment.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using 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 are not using an effective contraceptive method. 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 of the risks before starting Zeposia and will ask you to take a pregnancy test to confirm 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 must not become pregnant while taking Zeposia.

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

Breastfeeding

You must 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

The effect of Zeposia on the ability to drive and use machines is negligible or none.

Zeposia contains sodium

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

Zeposia contains potassium

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

3. How to take Zeposia

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

How much to take

When you first start taking Zeposia, you need to begin with a low dose and gradually increase it to reduce any effect that may slow your heart rate.

• You will receive a "starter pack" to help you begin treatment in this way. It contains:

• 4 light grey capsules containing 0.23 mg of ozanimod. You will take one of these capsules on days 1 to 4 of treatment.

• 3 light grey 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 maintenance dose of 0.92 mg of ozanimod from the "maintenance pack". You will continue treatment regularly 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 taken on alternate days.

How to take Zeposia

• Zeposia is taken by mouth.
• Swallow the capsule whole.
• You may 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 a hospital immediately. Take the medicine packaging and this leaflet with you.

If you forget to take Zeposia

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

If you stop taking Zeposia

• Do not stop taking Zeposia without first consulting your doctor.

• Consult your doctor about how to restart 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 restart treatment with the "starter pack".

Zeposia will remain 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).

Inform your doctor immediately if you think your MS is worsening after stopping Zeposia.

If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone 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

• low heart rate

• urinary tract infection

• increased 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

• infections of the nose or nasal passages, nasal cavity, mouth, throat (pharynx), or larynx caused by viruses

• low levels 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 lung infection)

• shingles (herpes zoster)

• cold sores or oral herpes (herpes simplex)

• headache

• low blood pressure

• swelling, especially of 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, and eyes, hyperbilirubinemia or high levels of bilirubin in the blood (jaundice)

• lung abnormalities that may cause shortness of breath.

Reporting of side effects

If you experience any type of side effect, talk to your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system included 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 stated on the blister and on the carton following “CAD”/“EXP”. The expiry date refers to the last day of the month indicated.
• Do not store above 25°C.
• Do not use this medicine if you notice any damage or signs of tampering with the packaging.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Zeposia

• The active substance 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 contents:

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).

Appearance of the product and contents of the pack

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

Pack sizes

• The treatment initiation pack is a carton 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
The Netherlands

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet:

Other sources of information

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 medicine by scanning with your mobile phone (smartphone) the QR code included on the outer packaging. You can also access this information at the following web address: www.zeposia-eu-pil.com.