BRUKINSA 80 mg Hard Capsules

Зміст інструкції

1. BRUKINSA 80 mg hard capsules
   1. What is BRUKINSA and what is it used for
   2. What you need to know before you take BRUKINSA
   3. How to take BRUKINSA
   4. Possible side effects
   5. How to store BRUKINSA
   6. Contents of the pack and other information

BRUKINSA 80 mg hard capsules

zanubrutinib
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is BRUKINSA and what is it used for

BRUKINSA is an anti-cancer drug that contains the active substance zanubrutinib. It belongs to
a class of drugs called protein kinase inhibitors. This drug works by blocking Bruton’s tyrosine
kinase, a protein present in the body that facilitates the growth and survival of cancer cells. By
blocking this protein, BRUKINSA reduces the number of cancer cells and slows tumour growth.
BRUKINSA is used for the treatment of Waldenström's macroglobulinaemia (also known as
lymphoplasmacytic lymphoma), a cancer that affects a type of white blood cells called B lymphocytes
which produce an excessive amount of a protein called IgM.
This drug is used when the disease has returned or previous treatment has not
worked, or in patients who cannot receive chemotherapy-based treatments together with
immunotherapy.
BRUKINSA is also used for the treatment of marginal zone lymphoma. This is a
type of cancer that also affects B lymphocytes or B cells. In marginal zone lymphoma, abnormal B
cells multiply too quickly and survive for too long. This can cause
enlargement of the organs involved in the body's natural defenses, such as lymph nodes
and the spleen. Abnormal B cells can also affect various organs such as the stomach, salivary
glands, thyroid, eyes, lungs, bone marrow and blood. Patients may experience fever, weight loss,
fatigue and night sweats, but also symptoms that depend on the location of
the lymphoma. This medicine is used in case of relapse or treatment failure.
BRUKINSA is also used to treat chronic lymphocytic leukaemia (CLL), another type of
cancer that affects B cells involving the lymph nodes. This medicine is used in
patients who have not been previously treated for CLL or when the disease has returned or if
it has not responded to previous treatment.

BRUKINSA is also used for the treatment of follicular lymphoma (FL), a slowly growing cancer
that affects B lymphocytes. When patients are affected by FL, the number of B lymphocytes is
excessive in the lymph nodes, spleen and bone marrow. BRUKINSA is administered together with
another drug called “obinutuzumab” when the disease has recurred, or when the drugs
previously used have not been effective.

2. What you need to know before you take BRUKINSA

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 had unusual bruising or bleeding in the past or if you are taking medicines or supplements that increase the risk of bleeding (see section “Other medicines and BRUKINSA”). If you have had surgery recently or are planning to have surgery, your doctor may ask you to stop taking BRUKINSA for a short period of time (3 to 7 days) before and after the surgery or dental procedure
• if you have an irregular heartbeat or have had an irregular heartbeat in the past or severe heart failure or if you have had any of the following symptoms: shortness of breath, weakness, dizziness, feeling lightheaded, chest pain or swollen legs
• if you have been told in the past that you are at high risk of developing infections. During treatment with BRUKINSA, you may develop viral, bacterial or fungal infections with the following possible symptoms: fever, chills, weakness, confusion, widespread body aches, cold or flu-like symptoms, feeling tired or short of breath, yellowing of the skin or eyes (jaundice).
• if you have ever had or may have hepatitis B. This is because BRUKINSA may cause hepatitis B to become active again. Patients will be carefully monitored by the doctor for signs of this infection before treatment begins
• if you have problems with your liver or kidneys
• if you have had any surgery recently, especially if this may affect the way you absorb food or medicines through your stomach or intestines
• if you recently have had a low number of red blood cells, white blood cells or platelets
• if you have had other cancers in the past, including skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma). Use sun protection

If any of the above situations apply to you or if you have doubts, talk to your doctor, pharmacist or
nurse before taking this medicine.

Tests and checks before and during treatment
Laboratory tests may show lymphocytosis, an increase in white blood cells (“lymphocytes”) in the
blood in the very early weeks of treatment. This is expected and may last for several months. This does not necessarily mean that your blood cancer is getting worse.
Your doctor will check your white blood cell count before and during treatment and, in rare
cases, may give you another medicine. Talk to your doctor to understand the meaning of
your test results.
Tumour lysis syndrome (TLS): during cancer treatment and, sometimes,
even without treatment, abnormal levels of chemicals in the blood have occurred caused
by the rapid breakdown of cancer cells. This can cause changes in kidney function, abnormal heartbeat or seizures. Your doctor or other healthcare professional may perform blood tests to check for TLS.

Children and adolescents
BRUKINSA should not be used in children and adolescents, as 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 you buy without a prescription, herbal medicines and supplements. This is because BRUKINSA may affect
how some medicines work. Also, some medicines may affect how BRUKINSA
works.

BRUKINSA may cause you to bleed more easily.Therefore, you must
tell your doctor if you are taking other medicines that increase the risk of bleeding. These
include medicines such as:

• acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen,
• anticoagulants such as warfarin, heparin and other medicines for treating or preventing blood clots,
• supplements that may increase the risk of bleeding such as fish oil, vitamin E or flaxseed. If you are in any of the conditions described above or if you have doubts, talk to your doctor, pharmacist or nurse before taking BRUKINSA.

Also tell your doctor if you are taking any of the following medicines- The effects of
BRUKINSA or other medicines may be affected if you take BRUKINSA together with
any of the following medicines:

• antibiotics used to treat bacterial infections - ciprofloxacin, clarithromycin, erythromycin, nafcillin or rifampicin
• medicines used to treat fungal infections - fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole
• medicines used to treat human immunodeficiency virus (HIV) infection - efavirenz, etravirine, indinavir, lopinavir, ritonavir, telaprevir
• medicines used to prevent nausea and vomiting associated with chemotherapy: aprepitant
• medicines used to treat depression: fluvoxamine, St John's wort
• medicines called kinase inhibitors for the treatment of other cancers - imatinib
• medicines used to treat high blood pressure or chest pain - bosentan, diltiazem, verapamil
• antiarrhythmic medicines for the heart- digoxina, dronedarone, quinidine
• medicines used to prevent seizures, to treat epilepsy or treat a painful condition of the face called trigeminal neuralgia - carbamazepine, mephenytoin, phenytoin
• medicines used to treat headaches (migraines and cluster headaches) - dihydroergotamine, ergotamine
• medicines used to treat extreme sleepiness and other sleep problems - modafinil
• medicines used to treat psychosis and Tourette's syndrome - primozide
• anaesthetics - alfentanil, fentanyl
• immunosuppressants - cyclosporine, sirolimus, tacrolimus

BRUKINSA with food
Grapefruit and Seville oranges should be consumed with caution around the times of
taking BRUKINSA, as they may increase the amount of BRUKINSA in the blood.

Pregnancy and breastfeeding
Do not become pregnant while taking this medicine. BRUKINSA must not be
used during pregnancy. It is not known whether BRUKINSA will harm the unborn child.
Women of childbearing potential must use a highly effective method of contraception during
treatment with BRUKINSA and for at least one month after treatment. In addition to hormonal contraceptives, such as pills or contraceptive devices, a barrier method of
contraception (e.g., condoms) should also be used.

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

Driving and using machines
After taking BRUKINSA you may feel tired or dizzy, which may affect
your ability to drive or operate machinery.

BRUKINSA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, that is to say it’s essentially “sodium-free”.

3. How to take BRUKINSA

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
The recommended dose is 320 mg (4 capsules) every day: 4 capsules once a day or
2 capsules in the morning and 2 in the evening.
Your doctor may adjust the dose.
Swallow the capsules with a glass of water, with food or between meals.
Take the capsules at about the same time each day.
BRUKINSA works best if swallowed whole. Swallow the capsules whole; do not open, crush or
chew them.

If you take more BRUKINSA than you should
If you take more BRUKINSA than you should, inform your doctor immediately. Bring with you the

If you forget to take BRUKINSA
If you forget a dose, take it at the next scheduled time, restoring the schedule defined by
your doctor. If you take BRUKINSA once a day, take the next dose the next day. If
you take the medicine twice a day, in the morning and in the evening, and forget the morning dose, take
the next dose in the evening. Do not take a double dose to make up for a missed
capsule. If you are not sure, ask your doctor, pharmacist or nurse when to take the dose
next.

If you stop taking BRUKINSA
Do not stop taking this medicine unless your doctor has told you to do so.
If you have any questions about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

Stop taking BRUKINSA and contact your doctor immediately if you notice any of the following side effects:

• itchy, bumpy rash, difficulty breathing, swelling of the face, lips, tongue or throat - this could be an allergic reaction to the medicine.

Contact your doctor immediately if you notice any of the side effects listed below.
Very common(may affect more than 1 in 10 people):

• fever, chills, widespread body aches, feeling tired, cold or flu-like symptoms, shortness of breath, needing to urinate frequently and with pain - these could be signs of an infection (viral, bacterial or fungal). These may include infections of the nose, sinuses or throat (upper respiratory tract infection), lung infection or urinary tract infection
• bruising or increased tendency to bruise; contusions
• bleeding
• muscle and bone pain
• skin rash
• lung infection (lower respiratory tract infection)
• dizziness
• diarrhoea; your doctor may need to give you fluids and a salt replacement or another medicine
• fatigue
• high blood pressure
• constipation
• blood in the urine
• blood tests showing a decrease in the number of blood cells. Your doctor will perform blood tests during treatment with BRUKINSA to check the number of blood cells.

Common(may affect up to 1 in 10 people):

• swelling of hands, ankles or feet
• nosebleeds
• itchy skin
• small, pinpoint bleeding spots under the skin
• fast heartbeat, skipped heartbeats, weak or irregular pulse, feeling lightheaded, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
• weakness
• low white blood cell count with fever (febrile neutropenia)

Uncommon side effects(may affect up to 1 in 100 people):

• reactivation of hepatitis B (if you have had hepatitis B, it may return)
• intestinal bleeding (blood in the stool)
• abnormal levels of chemicals in the blood have occurred due to the rapid breakdown of cancer cells during cancer treatment and sometimes even without treatment (tumour lysis syndrome)

Not known:

• Redness and peeling of the skin over a wide area of the body, which may be itchy or painful (generalized exfoliative dermatitis)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store BRUKINSA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date, stated on the package and bottle after “Exp”.
The expiry date refers to the last day of that month.
This medicine does not require any particular storage conditions.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What BRUKINSA contains

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

Description of the appearance of BRUKINSA and contents of the pack
BRUKINSA is a hard capsule of white to off-white color, with "ZANU 80” imprinted in
black ink on one side. The capsules are supplied in a plastic bottle with a child-resistant closure. Each bottle contains 120 hard capsules.

Marketing Authorisation Holder
BeiGene Ireland Ltd.
10 Earlsfort Terrace
Dublin 2
D02 T380
Ireland
Tel. +353 1 566 7660
E-mail [email protected]

Manufacturer
BeiGene Switzerland GmbH – Dutch Branch
Evert van de Beekstraat 1, 104
1118 CL Schiphol
Netherlands
BeiGene Germany GmbH
Georges-Köhler-Str. 2, 79539 Lörrach
Germany
BeiGene Netherlands B.V.
Evert van de Beekstraat 1, 104
1118 CL Schiphol
Netherlands
For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
BeiGene Belgium SRL
Tél/Tel: 0800 774 047

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

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

Luxembourg/Luxemburg
BeiGene France sarl
Tél/Tel: 0800 85520

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

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

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

Deutschland
Beigene Germany GmbH
Tel: 0800 200 8144

Danmark
BeiGene Sweden AB
Tlf: 808 10 660

Nederland
BeiGene Netherlands B.V.
Tel: 08000 233 408

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
BeiGene Sweden AB
Tlf: 800 31 491

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

Österreich
BeiGene Austria GmbH
Tel: 0800 909 638

España
BeiGene Spain, SLU
Tel: 9000 31 090

Polska
BeiGene Poland sp. z o. o.
Tel.: 8000 80 952

France
BeiGene France sarl
Tél: 080 554 3292

Portugal
BeiGene Portugal, Unipessoal Lda
Tel: 800 210 376

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

Ireland
BeiGene 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
BeiGene Sweden AB
Sími: 800 4418

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

Italia
BeiGene Italy Srl
Tel: 800 588 525

Suomi/Finland
BeiGene Sweden AB
Puh/Tel: 0800 774 047

Κύπρος
Swixx Biopharma Μ.Α.Ε

Sverige
BeiGene Sweden AB
Τηλ: +30 214 444 9670 Puh/Tel: 0200 810 337

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

United Kingdom (Northern Ireland)
BeiGene UK Ltd
Tel: 0800 917 6799

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.