zanubrutinib: package leaflet

BRUKINSA is an anticancer medicine that contains the active substance zanubrutinib. It belongs to a class of medicines called protein kinase inhibitors. This medicine works by blocking Bruton's tyrosine kinase, a protein in the body that helps cancer cells grow and survive. By blocking this protein, BRUKINSA reduces the number of cancer cells and slows down the worsening of the cancer.

BRUKINSA is used to treat Waldenström’s macroglobulinaemia (also known as lymphoplasmacytic lymphoma), a cancer affecting a type of white blood cells called B lymphocytes or B cells that make too much of a protein called IgM. This medicine is used when the disease has come back, or treatment has not worked or in patients who cannot have chemotherapy together with an antibody.

BRUKINSA is also used to treat marginal zone lymphoma. This is a type of cancer that also affects B lymphocytes or B cells. In marginal zone lymphoma, the abnormal B cells multiply too quickly and live for too long. This may cause enlargement of organs that are part of body’s natural defences such as lymph node and spleen. The abnormal B cells may also affect various organs, such as stomach, salivary gland, thyroid, eyes, lungs, bone marrow and blood. Patients may have fever, weight loss, tiredness and night sweats, but also symptoms that depend on where the lymphoma develop. This medicine is used when the disease has come back, or treatment has not worked.

BRUKINSA is also used to treat chronic lymphocytic leukaemia (CLL), another type of cancer affecting B cells that involves the lymph nodes. This medicine is used in patients who have not previously been treated for CLL or when the disease has come back or has not responded to previous treatment.

BRUKINSA is also used to treat follicular lymphoma (FL). FL is a slow growing cancer that affects the B lymphocytes. When you have FL, you have too many of these B lymphocytes in your lymph nodes, spleen, and bone marrow. BRUKINSA is taken together with another medicine called ‘obinutuzumab’ when the disease has come back or when previously used medicines have not been effective.

Do not take BRUKINSA

• if you are allergic to zanubrutinib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking BRUKINSA:
- if you have ever had unusual bruising or bleeding or are on any medicines or supplements that increase your risk of bleeding (see section “Other medicines and BRUKINSA”). If you have had recent surgery or plan to have surgery, your doctor may ask you to stop taking BRUKINSA for a short time (3 to 7 days) before and after your surgery or dental procedure
- if you have an irregular heartbeat or have a history of irregular heartbeat or severe heart failure, or if you have any of the following: shortness of breath, weakness, dizziness, light- headedness, fainting or near fainting, chest pain or swollen legs
- if you have ever been advised that you are at higher risk of infections. You may experience viral, bacterial, or fungal infections during treatment with BRUKINSA with the following possible symptoms: fever, chills, weakness, confusion, body aches, cold or flu symptoms, feel tired or feel short of breath, yellowing of the skin or eyes (jaundice).
- if you have ever had or might have hepatitis B. This is because BRUKINSA could cause hepatitis B to become active again. Patients will be carefully checked by their doctor for signs of this infection before treatment is started
- if you have liver or kidney problems
- if you have recently had any surgery, especially if it might affect how you absorb food or medicines from your stomach or gut
- if you recently had low counts of red blood cells, infection-fighting cells or platelets in your blood
- if you had other carcinomas in the past including skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma). Please use sun protection

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking this medicine.

Tests and check-ups before and during treatment

Laboratory tests may show lymphocytosis, an increase in white blood cells (lymphocytes) in your blood in the first few weeks of treatment. This is expected and may last for a few months. This does not necessarily mean that your blood cancer is getting worse. Your doctor will check your blood counts before and during the treatment and in rare cases the doctor may give you another medicine.
Talk to your doctor about what your test results mean.
Tumour lysis syndrome (TLS): Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have occurred during treatment of cancer and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your doctor or another healthcare provider may do blood tests to check for TLS.

Children and adolescents

BRUKINSA should not be used in patients younger than 18 years of age, because it is unlikely to work.

Other medicines and BRUKINSA

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription, herbal medicines and supplements. This is because BRUKINSA may affect the way some medicines work. Also, some medicines can affect the way BRUKINSA works.

BRUKINSA may make you bleed more easily. This means you should tell your doctor if you take other medicines that increase your risk of bleeding. This includes medicines such as:
- acetylsalicylic acid such as aspirin and non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen and naproxen,
- anticoagulants such as warfarin, heparin and other medicines for treating or preventing blood clots,
- supplements that may increase your risk of bleeding such as fish oil, vitamin E or flaxseed.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking BRUKINSA.

Also tell your doctor if you take any of the following medicines – The effects of BRUKINSA or other medicines may be influenced if you take BRUKINSA together with any of the following medicines:
- antibiotics to treat bacterial infections – ciprofloxacin, clarithromycin, erythromycin, nafcillin or rifampicin
- medicines for fungal infections – fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole
- medicines for HIV infection – efavirenz, etravirine, indinavir, lopinavir, ritonavir, telaprevir
- medicine to prevent nausea and vomiting associated with chemotherapy - aprepitant
- medicines for depression – fluvoxamine, St. John’s wort
- medicine called kinase inhibitors for treatment of other cancers – imatinib
- medicines for high blood pressure or chest pain – bosentan, diltiazem, verapamil
- heart medicines/anti-arrhythmics – digoxin, dronedarone, quinidine
- medicines to prevent seizures, to treat epilepsy, or to treat a painful condition of the face called trigeminal neuralgia – carbamazepine, mephenytoin, phenytoin
- medicines for migraines and cluster headaches - dihydroergotamine, ergotamine
- medicine for extreme sleepiness and other sleep problems - modafinil
- medicine for psychosis and Tourette disorder - pimozide
- medicines for anaesthesia – alfentanil, fentanyl
- medicines called immunosuppressive agents – ciclosporin, sirolimus, tacrolimus

BRUKINSA with food

Tell your doctor if you consume grapefruit or Seville oranges (bitter oranges) because they can increase the amount of BRUKINSA in your blood.

Pregnancy and breast-feeding

Do not get pregnant while you are taking this medicine. BRUKINSA should not be used during pregnancy. It is not known if BRUKINSA will harm your unborn baby.

Women of childbearing age must use a highly effective method of birth control during treatment with BRUKINSA and for least one month after treatment. A barrier method of contraception (e.g., condoms) must be used with hormonal contraceptives such as birth control pills or devices.

• Tell your doctor immediately if you become pregnant.
• Do not breast-feed while you are taking this medicine. BRUKINSA may pass into breast milk.

Driving and using machines

You may feel tired or dizzy after taking BRUKINSA, which may affect your ability to drive or use machines. If you feel tired or dizzy after taking BRUKINSA, you must not drive or use machines.

BRUKINSA contains sodium

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

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

The recommended dose is 320 mg (4 capsules) each day, either as 4 capsules once daily or 2 capsules in the morning and 2 in the evening.
Your doctor may adjust the dose.
Take the capsules by mouth with a glass of water with food or between meals.
Take the capsules about the same time each day.
BRUKINSA works best when it is swallowed whole. Therefore, swallow the capsules whole. Do not open, break or chew them.

If you take more BRUKINSA than you should

If you take more BRUKINSA than you should, talk to a doctor straight away. Take the capsule packet and this leaflet with you.

If you forget to take BRUKINSA

If you miss a dose, take it at the next scheduled time with a return to the normal schedule. If you take BRUKINSA once per day, take your next dose the following day. If you take the medicine twice a day, in the morning and in the evening and you forgot to take it in the morning, take your next dose in the evening. Do not take a double dose to make up for a forgotten dose. If you are not sure, talk to your doctor, pharmacist or nurse about when to take your next dose.

If you stop taking BRUKINSA

Do not stop taking this medicine unless your doctor tells you.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking BRUKINSA and tell a doctor straight away if you notice any of the following side effects:

• itchy bumpy rash, difficulty breathing, swelling of your face, lips, tongue or throat – you may be having an allergic reaction to the medicine.

Tell a doctor straight away if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people):
- fever, chills, body aches, feeling tired, cold or flu symptoms, being short of breath, frequent and painful urination – these could be signs of an infection (viral, bacterial or fungal). These could include infections of the nose, sinus or throat (upper respiratory tract infection), pneumonia, or urinary tract.
- bruising or increased tendency of bruising; contusions
- bleeding
- muscle and bone aches
- skin rash
- diarrhoea; your doctor may need to give you a fluid and salt replacement or another medicine
- cough
- fatigue
- high blood pressure
- constipation
- feeling sick (nausea)
- dizziness
- blood in urine
- blood tests showing a reduced number of blood cells. Your doctor should do blood tests during treatment with BRUKINSA to check the number of your blood cells.

Common (may affect up to 1 in 10 people):
- swollen hands, ankles or feet
- nosebleed
- itching of the skin
- infection of the lung (lower respiratory tract infection)
- small bleeding spots under the skin
- fast heart rate, missed heart beats, weak or uneven pulse, lightheadedness, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
- weakness
- low white blood cell count with fever (febrile neutropenia)

Uncommon (may affect up to 1 in 100 people):
- reactivation of hepatitis B (if you had experienced hepatitis B, it may come back)
- intestinal bleeding (blood in stool)
- unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have occurred during treatment of cancer and sometimes even without treatment (tumour lysis syndrome)

Unknown:
- redness and shedding of skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis generalized)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. 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.

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 carton and the bottle after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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.

What BRUKINSA contains

• The active substance is zanubrutinib. Each hard capsule contains 80 mg of zanubrutinib.
• The other ingredients are:
• capsule content: microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate (E487), silica colloidal anhydrous and magnesium stearate. See section 2 “BRUKINSA contains sodium”.
• capsule shell: gelatin and titanium dioxide (E171)
• printing ink: shellac glaze (E904), iron oxide black (E172) and propylene glycol (E1520).

What BRUKINSA looks like and contents of the pack

BRUKINSA is a white to off-white hard capsule of 22 mm in length, marked with “ZANU 80” in black ink on one side.

The capsules are provided in a plastic bottle with a child resistant closure. Each bottle contains 120 hard capsules.

Marketing Authorisation Holder

BeOne Medicines Ireland Limited.
10 Earlsfort Terrace
Dublin 2
D02 T380
Ireland
Tel.
+353 1 566 7660
E-mail mailto: beone.ireland@beonemed.com

Manufacturer

BeOne Medicines GmbH I, Dutch Branch
Evert van de Beekstraat 1, 104
1118 CL Schiphol
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
BeOne Medicines Belgium
Tél/Tel: 0800 89 307

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
BeOne Medicines Belgium
Tél/Tel: 800 85520

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
BeOne Medicines, Denmark Branch
Tlf: 808 10 660

Malta
Swixx Biopharma S.M.S.A.
Tel: +30 214 444 9670

Deutschland
BeOne Medicines Germany GmbH
Tel: 0800 200 8144

Nederland
BeOne Medicines Netherlands B.V.
Tel: 08000 233 408

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
BeOne Medicines Sweden ABTlf: 800 31 491

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Tel: +30 214 444 9670

Österreich
BeOne Medicines Austria GmbH
Tel: 0800 909 638
España
BeOne Medicines ESP, S.L.U.
Tel: 9000 31 090

Polska
BeOne Medicines Poland sp. z o. o.
Tel.: 8000 80 952

France
BeOne Medicines France Sarl
Tél: 080 554 3292

Portugal
BeOne Medicines Portugal, Unipessoal Lda.
Tel: 800 210 376

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

Ireland
MeOne Medicines UK, Ltd
Tel: 1800 812 061
România
Swixx Biopharma S.R.L
Tel: +40 37 1530 850

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
BeOne Medicines Sweden ABSími: 800 4418

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
BeOne Medicines Italy S.r.l
Tel: 800 588 525

Suomi/Finland
BeOne Medicines Sweden ABPuh/Tel: 0800 774

Κύπρος
Swixx Biopharma Μ.Α.Ε
Tel: +30 214 444 9670

Sverige
BeOne Medicines Sweden AB
Puh/Tel: 0200 810 337

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last revised in

Other sources of information

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

BRUKINSA is an anticancer medicine that contains the active substance zanubrutinib. It belongs to a class of medicines called protein kinase inhibitors. This medicine works by blocking Bruton's tyrosine kinase, a protein in the body that helps cancer cells grow and survive. By blocking this protein, BRUKINSA reduces the number of cancer cells and slows down the worsening of the cancer.

BRUKINSA is used to treat Waldenström’s macroglobulinaemia (also known as lymphoplasmacytic lymphoma), a cancer affecting a type of white blood cells called B lymphocytes or B cells that make too much of a protein called IgM. This medicine is used when the disease has come back, or treatment has not worked or in patients who cannot have chemotherapy together with an antibody.

BRUKINSA is also used to treat marginal zone lymphoma. This is a type of cancer that also affects B lymphocytes or B cells. In marginal zone lymphoma, the abnormal B cells multiply too quickly and live for too long. This may cause enlargement of organs that are part of body’s natural defences such as lymph node and spleen. The abnormal B cells may also affect various organs, such as stomach, salivary gland, thyroid, eyes, lungs, bone marrow and blood. Patients may have fever, weight loss, tiredness and night sweats, but also symptoms that depend on where the lymphoma develop. This medicine is used when the disease has come back, or treatment has not worked.

BRUKINSA is also used to treat chronic lymphocytic leukaemia (CLL), another type of cancer affecting B cells that involves the lymph nodes. This medicine is used in patients who have not previously been treated for CLL or when the disease has come back or has not responded to previous treatment.

BRUKINSA is also used to treat follicular lymphoma (FL). FL is a slow growing cancer that affects the B lymphocytes. When you have FL, you have too many of these B lymphocytes in your lymph nodes, spleen, and bone marrow. BRUKINSA is taken together with another medicine called ‘obinutuzumab’ when the disease has come back or when previously used medicines have not been effective.

Do not take BRUKINSA

• if you are allergic to zanubrutinib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking BRUKINSA:
- if you have ever had unusual bruising or bleeding or are on any medicines or supplements that increase your risk of bleeding (see section “Other medicines and BRUKINSA”). If you have had recent surgery or plan to have surgery, your doctor may ask you to stop taking BRUKINSA for a short time (3 to 7 days) before and after your surgery or dental procedure
- if you have an irregular heartbeat or have a history of irregular heartbeat or severe heart failure, or if you have any of the following: shortness of breath, weakness, dizziness, light- headedness, fainting or near fainting, chest pain or swollen legs
- if you have ever been advised that you are at higher risk of infections. You may experience viral, bacterial, or fungal infections during treatment with BRUKINSA with the following possible symptoms: fever, chills, weakness, confusion, body aches, cold or flu symptoms, feel tired or feel short of breath, yellowing of the skin or eyes (jaundice).
- if you have ever had or might have hepatitis B. This is because BRUKINSA could cause hepatitis B to become active again. Patients will be carefully checked by their doctor for signs of this infection before treatment is started
- if you have liver or kidney problems
- if you have recently had any surgery, especially if it might affect how you absorb food or medicines from your stomach or gut
- if you recently had low counts of red blood cells, infection-fighting cells or platelets in your blood
- if you had other carcinomas in the past including skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma). Please use sun protection

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking this medicine.

Tests and check-ups before and during treatment

Laboratory tests may show lymphocytosis, an increase in white blood cells (lymphocytes) in your blood in the first few weeks of treatment. This is expected and may last for a few months. This does not necessarily mean that your blood cancer is getting worse. Your doctor will check your blood counts before and during the treatment and in rare cases the doctor may give you another medicine.
Talk to your doctor about what your test results mean.

Tumour lysis syndrome (TLS): Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have occurred during treatment of cancer and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your doctor or another healthcare provider may do blood tests to check for TLS.

Children and adolescents

BRUKINSA should not be used in patients younger than 18 years of age, because it is unlikely to work.

Other medicines and BRUKINSA

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription, herbal medicines and supplements. This is because BRUKINSA may affect the way some medicines work. Also, some medicines can affect the way BRUKINSA works.

BRUKINSA may make you bleed more easily. This means you should tell your doctor if you take other medicines that increase your risk of bleeding. This includes medicines such as:
- acetylsalicylic acid such as aspirin and non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen and naproxen,
- anticoagulants such as warfarin, heparin and other medicines for treating or preventing blood clots,
- supplements that may increase your risk of bleeding such as fish oil, vitamin E or flaxseed.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking BRUKINSA.

Also tell your doctor if you take any of the following medicines – The effects of BRUKINSA or other medicines may be influenced if you take BRUKINSA together with any of the following medicines:
- antibiotics to treat bacterial infections – ciprofloxacin, clarithromycin, erythromycin, nafcillin or rifampicin
- medicines for fungal infections – fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole
- medicines for HIV infection – efavirenz, etravirine, indinavir, lopinavir, ritonavir, telaprevir
- medicine to prevent nausea and vomiting associated with chemotherapy - aprepitant
- medicines for depression – fluvoxamine, St. John’s wort
- medicine called kinase inhibitors for treatment of other cancers – imatinib
- medicines for high blood pressure or chest pain – bosentan, diltiazem, verapamil
- heart medicines/anti-arrhythmics – digoxin, dronedarone, quinidine
- medicines to prevent seizures, to treat epilepsy, or to treat a painful condition of the face called trigeminal neuralgia – carbamazepine, mephenytoin, phenytoin
- medicines for migraines and cluster headaches - dihydroergotamine, ergotamine
- medicine for extreme sleepiness and other sleep problems - modafinil
- medicine for psychosis and Tourette disorder - pimozide
- medicines for anaesthesia – alfentanil, fentanyl
- medicines called immunosuppressive agents – ciclosporin, sirolimus, tacrolimus

BRUKINSA with food

Tell your doctor if you consume grapefruit or Seville oranges (bitter oranges) because they can increase the amount of BRUKINSA in your blood.

Pregnancy and breast-feeding

Do not get pregnant while you are taking this medicine. BRUKINSA should not be used during pregnancy. It is not known if BRUKINSA will harm your unborn baby.

Women of childbearing age must use a highly effective method of birth control during treatment with BRUKINSA and for least one month after treatment. A barrier method of contraception (e.g., condoms) must be used with hormonal contraceptives such as birth control pills or devices.

• Tell your doctor immediately if you become pregnant.
• Do not breast-feed while you are taking this medicine. BRUKINSA may pass into breast milk.

Driving and using machines

You may feel tired or dizzy after taking BRUKINSA, which may affect your ability to drive or use machines. If you feel tired or dizzy after taking BRUKINSA, you must not drive or use machines.

BRUKINSA contains sodium and lactose

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

This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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

The recommended dose is 320 mg (2 tablets) each day, either as 2 tablets once daily or 1 tablet in the morning and 1 in the evening.
Your doctor may adjust the dose.
Take the tablets by mouth with a glass of water with food or between meals.
Take the tablets about the same time each day.
The tablets can be divided into two equal halves. Your healthcare provider will tell you if you need to divide the tablets.
Do not chew or crush them.

If you take more BRUKINSA than you should

If you take more BRUKINSA than you should, talk to a doctor straight away. Take the tablet packet and this leaflet with you.

If you forget to take BRUKINSA

If you miss a dose, take it at the next scheduled time with a return to the normal schedule. If you take BRUKINSA once per day, take your next dose the following day. If you take the medicine twice a day, in the morning and in the evening and you forgot to take it in the morning, take your next dose in the evening. Do not take a double dose to make up for a forgotten dose. If you are not sure, talk to your doctor, pharmacist or nurse about when to take your next dose.

If you stop taking BRUKINSA

Do not stop taking this medicine unless your doctor tells you.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking BRUKINSA and tell a doctor straight away if you notice any of the following side effects:

• itchy bumpy rash, difficulty breathing, swelling of your face, lips, tongue or throat – you may be having an allergic reaction to the medicine.

Tell a doctor straight away if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people):
- fever, chills, body aches, feeling tired, cold or flu symptoms, being short of breath, frequent and painful urination – these could be signs of an infection (viral, bacterial or fungal). These could include infections of the nose, sinus or throat (upper respiratory tract infection), pneumonia, or urinary tract.
- bruising or increased tendency of bruising; contusions
- bleeding
- muscle and bone aches
- skin rash
- diarrhoea; your doctor may need to give you a fluid and salt replacement or another medicine
- cough
- fatigue
- high blood pressure
- constipation
- feeling sick (nausea)
- dizziness
- blood in urine
- blood tests showing a reduced number of blood cells. Your doctor should do blood tests during treatment with BRUKINSA to check the number of your blood cells.

Common (may affect up to 1 in 10 people):
- swollen hands, ankles or feet
- nosebleed
- itching of the skin
- infection of the lung (lower respiratory tract infection)
- small bleeding spots under the skin
- fast heart rate, missed heart beats, weak or uneven pulse, lightheadedness, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
- weakness
- low white blood cell count with fever (febrile neutropenia)

Uncommon (may affect up to 1 in 100 people):
- reactivation of hepatitis B (if you had experienced hepatitis B, it may come back)
- intestinal bleeding (blood in stool)
- unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have occurred during treatment of cancer and sometimes even without treatment (tumour lysis syndrome)

Unknown:
- redness and shedding of skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis generalized)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. 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.

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 carton and the bottle after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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.

What BRUKINSA contains

• The active substance is zanubrutinib. Each film-coated tablet contains 160 mg of zanubrutinib.
• The other ingredients are:
• tablet content: lactose monohydrate, croscarmellose sodium, sodium lauryl sulfate (E487), colloidal silicon dioxide, povidone, microcrystalline cellulose, and magnesium stearate. See section 2 “BRUKINSA contains sodium and lactose”.
• film coating: hypromellose, titanium dioxide (E171), triacetin, Brilliant blue FCF aluminium lake (E133) and Indigo carmine aluminium lake (E132).

What BRUKINSA looks like and contents of the pack

BRUKINSA is an oval, blue, film-coated tablet of 16 mm in length and 7.8 mm of width, with letters “zanu” debossed on one side and a score line on the other side. The tablet can be divided into two equal halves.

The tablets are provided in a plastic bottle with a child resistant closure. Each carton contains one bottle of 60 film-coated tablets.

Marketing Authorisation Holder

BeOne Medicines Ireland Limited.
10 Earlsfort Terrace
Dublin 2
D02 T380

Ireland
Tel.
+353 1 566 7660
E-mail mailto: beone.ireland@beonemed.com

Manufacturer

BeOne Medicines I GmbH, Dutch Branch
Evert van de Beekstraat 1, 104
1118 CL Schiphol
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
BeOne Medicines Belgium
Tél/Tel: 0800 89 307

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
BeOne Medicines Belgium
Tél/Tel: 800 85520

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
BeOne Medicines, Denmark Branch
Tlf: 808 10 660

Malta
Swixx Biopharma S.M.S.A.
Tel: +30 214 444 9670

Deutschland
BeOne Medicines Germany GmbH
Tel: 0800 200 8144

Nederland
BeOne Medicines Netherlands B.V.
Tel: 08000 233 408

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
BeOne Medicines Sweden AB
Tlf: 800 31 491

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Tel: +30 214 444 9670

Österreich
BeOne Medicines Austria GmbH
Tel: 0800 909 638
España
BeOne Medicines ESP, S.L.U
Tel: 9000 31 090

Polska
BeOne Medicines Poland sp. z o. o.
Tel.: 8000 80 952

France
BeOne Medicines France Sarl Tél: 080 554 3292

Portugal
BeOne Medicines Portugal, Unipessoal Lda.
Tel: 800 210 376

Hrvatska
Swixx Biopharma d.o.o.
România
Swixx Biopharma S.R.L

Tel: +385 1 2078 500

Ireland
BeOne Medicines UK, Ltd
Tel: 1800 812 061

Tel: +40 37 1530 850

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
BeOne Medicines Sweden AB
Sími: 800 4418

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
BeOne Medicines Italy Srl
Tel: 800 588 525

Suomi/Finland
BeOne Medicines Sweden AB
Puh/Tel: 0800 774 047

Κύπρος
Swixx Biopharma Μ.Α.Ε
Tel: +30 214 444 9670

Sverige
BeOne Medicines Sweden AB
Puh/Tel: 0200 810 337

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last revised in

Other sources of information

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

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS
OF THE MARKETING AUTHORISATION(S)

Scientific conclusions
Taking into account the PRAC Assessment Report on the PSUR(s) for zanubrutinib, the scientific conclusions of PRAC are as follows:
In view of available data on Nausea from clinical trials, spontaneous and solicited reports including cases with a dose dependant pattern and/or close temporal relationship, and in view of a possible class effect, the PRAC Rapporteur considers a causal relationship between zanubrutinib and nausea is at least a reasonable possibility. The PRAC Rapporteur concluded that the product information of products containing zanubrutinib should be amended accordingly.
Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation.
Grounds for the variation to the terms of the marketing authorisation(s)
On the basis of the scientific conclusions for zanubrutinib the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing zanubrutinib is unchanged subject to the proposed changes to the product information The CHMP recommends that the terms of the marketing authorisation(s) should be varied.