Brukinsa 80 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

BRUKINSA 80 mg hard capsules

zanubrutinib

This medicine is subject to additional monitoring, which will allow for faster detection of new safety information. You can help by reporting any side effects you may experience. Information on how to report such side effects is included at the end of section 4.

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

• Keep this leaflet, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally and must not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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 delays the progression of cancer.

BRUKINSA is used to treat Waldenström's macroglobulinaemia (also known as lymphoplasmacytic lymphoma), a cancer that affects a type of white blood cells called B-cells, which produce too much of a protein called IgM.

This medicine is used when the disease has relapsed, previous treatment has not worked, or in patients who cannot receive chemotherapy in combination with an antibody.

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-lymphocytes multiply too quickly and live too long, which can lead to the enlargement of certain organs that are part of the body's natural defenses, such as the lymph nodes and spleen. Abnormal B-lymphocytes can also affect various organs, including the stomach, salivary glands, thyroid, eyes, lungs, bone marrow, and blood. Patients may experience fever, weight loss, fatigue, and night sweats, as well as symptoms depending on where the lymphoma develops. This medicine is used when the disease has relapsed or previous treatment has not been effective.

BRUKINSA is also used to treat chronic lymphocytic leukaemia (CLL), another type of B-cell cancer that affects the lymph nodes. This medicine is used in patients who have not previously received treatment for CLL, in cases of disease relapse, or when the disease has not responded to prior treatment.

BRUKINSA is also used to treat follicular lymphoma (FL). FL is a slow-growing cancer that affects B-lymphocytes. FL causes an excess of these B-lymphocytes in the lymph nodes, spleen, and bone marrow. BRUKINSA is taken together with another medicine called obinutuzumab when the disease has relapsed or when previously used medicines have not worked.

2. What you need to know before starting to take BRUKINSA

Do not take BRUKINSA

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take BRUKINSA:

• if you have ever had unusual bruising or bleeding, or if you are taking medications or supplements that increase the risk of bleeding (see section “Other medicines and BRUKINSA”); if you have recently undergone or are scheduled for surgery, your doctor may instruct you to stop taking BRUKINSA for a short period (3 to 7 days) before and after the surgical or dental procedure;
• if you have an irregular heartbeat or a history of irregular heartbeat or severe heart failure, or if you experience any of the following symptoms: shortness of breath, weakness, dizziness, lightheadedness, fainting or near-fainting, chest pain, or swollen legs;
• if you have ever been told you are at increased risk of infections. You may develop viral, bacterial, or fungal infections during treatment with BRUKINSA, with possible symptoms including: fever, chills, weakness, confusion, body aches, cold or flu-like symptoms, feeling tired or short of breath, or yellowing of the skin or eyes (jaundice);
• if you have ever had or may have hepatitis B. This is because BRUKINSA can reactivate hepatitis B. Before starting treatment, patients will be carefully evaluated by their doctor for signs of this infection;
• if you have liver or kidney problems;
• if you have recently undergone surgery, especially if it could affect how your stomach or intestines absorb food or medicines;
• if you have recently had low blood counts of red blood cells, infection-fighting cells, or platelets;
• if you have had other carcinomas in the past, such as skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma), use sun protection.

If you are in any of the above situations (or are unsure), consult your doctor, pharmacist, or nurse before starting to take this medicine.

Tests and monitoring before and during treatment

Blood tests or laboratory analyses may reveal lymphocytosis, an increase in white blood cells called "lymphocytes" in the blood during the first weeks of treatment. This effect is expected and may last for several months. This does not necessarily mean that the blood cancer is worsening. Your doctor will check your blood counts before and during treatment and, in rare cases, may need to administer another medication. Discuss with your doctor what your test results mean.

Tumor lysis syndrome (TLS): During cancer treatment, and sometimes even without treatment, unusual levels of certain chemicals in the blood may occur due to the rapid breakdown of cancer cells. This can lead to impaired kidney function, irregular heartbeat, or seizures. Your doctor or other healthcare professional may perform blood tests to detect TLS.

Children and adolescents

BRUKINSA must not be used in patients under 18 years of age, as it is unlikely to be effective.

Other medicines and BRUKINSA

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter medicines, herbal remedies, and supplements. This is because BRUKINSA may affect how some medicines work. In addition, some medicines may affect how BRUKINSA works.

BRUKINSA may increase the risk of bleeding. This means you should inform your doctor if you are taking other medicines that increase the risk of bleeding. These include:

• acetylsalicylic acid, such as aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen,
• anticoagulants, such as warfarin, heparin, and other medicines used to treat or prevent 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 above situations (or are unsure), consult your doctor, pharmacist, or nurse before starting BRUKINSA.

Also, inform your doctor if you are taking any of the following medicines. The effects of BRUKINSA or other medicines may be altered if BRUKINSA is taken together with any of the following:

• antibiotics for bacterial infections: ciprofloxacin, clarithromycin, erythromycin, nafcillin, or rifampicin
• antifungal medicines: fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole
• HIV medicines: efavirenz, etravirine, indinavir, lopinavir, ritonavir, telaprevir
• medicines to prevent nausea and vomiting associated with chemotherapy: aprepitant
• antidepressants: fluvoxamine, St. John's wort
• kinase inhibitor medicines for the treatment of other cancers: imatinib
• medicines for high blood pressure or chest pain: bosentan, diltiazem, verapamil
• heart medicines/antiarrhythmics: digoxin, dronedarone, quinidine
• medicines to prevent seizures, treat epilepsy, or treat a painful facial condition called trigeminal neuralgia: carbamazepine, mephenytoin, phenytoin
• medicines for migraines and cluster headaches: dihydroergotamine, ergotamine
• medicines for excessive sleepiness and other sleep disorders: modafinil
• medicines for psychosis and Tourette’s disorder: pimozide
• anaesthetics: alfentanil, fentanyl
• medicines known as immunosuppressants: ciclosporin, sirolimus, tacrolimus

Taking BRUKINSA with food

Inform your doctor if you consume grapefruit or bitter oranges, as they may increase the amount of BRUKINSA in your blood.

Pregnancy and breastfeeding

You must not become pregnant while taking this medicine. BRUKINSA must not be used during pregnancy. It is unknown whether BRUKINSA may harm the unborn baby.

Women of childbearing potential must use a highly effective method of contraception during treatment with BRUKINSA and for at least one month after treatment ends. A barrier method (e.g., condoms) should be used in combination with hormonal contraceptives such as oral contraceptive pills or contraceptive devices.

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

Driving and using machines

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

BRUKINSA contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free".

3. How to take BRUKINSA

Follow exactly the instructions provided by your doctor or pharmacist for taking this medicine. If in doubt, consult your doctor or pharmacist again.

The recommended dose is 320 mg (4 capsules) per day, either as 4 capsules once daily or as 2 capsules in the morning and 2 capsules in the evening.

Your doctor may adjust your dose.

Take the capsules orally with a glass of water, with food or between meals.

Take the capsules at approximately the same time each day.

BRUKINSA works best when 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 prescribed, consult a doctor immediately. Bring the capsule packaging and this leaflet with you.

If you forget to take BRUKINSA

If you miss a dose, take it at the next scheduled time and then return to your normal schedule the following day. If you take BRUKINSA once daily, take the next dose the following day. If you take the medicine twice daily, in the morning and evening, and you miss the morning dose, take the next dose in the evening. Do not take a double dose to make up for missed capsules. If you are unsure, consult your doctor, pharmacist, or nurse about when to take the next dose.

If you stop taking BRUKINSA

Do not stop treatment with this medicine unless instructed to do so by your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Stop taking BRUKINSA and immediately inform your doctor if you experience any of the following adverse effects:

• Itchy, rough rash, difficulty breathing, swelling of the face, lips, tongue, or throat: you may be experiencing an allergic reaction to the medicine.

Contact your doctor immediately 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, flu-like or cold symptoms, shortness of breath, frequent and painful urination: these may be symptoms of an infection (caused by viruses, bacteria, or fungi). These may include infections of the nose, sinuses, or throat (upper respiratory tract infection), pneumonia, or urinary tract infections.
• Bruising or increased tendency to bruise; contusions
• Bleeding
• Muscle and bone pain
• Skin rash
• Diarrhea; your doctor may need to provide fluid and electrolyte replacement or another medication
• Cough
• Fatigue
• High blood pressure
• Constipation
• Dizziness
• Blood in the urine
• Decreased number of blood cells in blood tests. Your doctor should perform regular blood tests during treatment with BRUKINSA to monitor your blood cell counts.

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

• Swelling of the hands, ankles, or feet
• Nosebleeds
• Itching of the skin
• Lung infection (lower respiratory tract infection)
• Small bleeding spots under the skin
• Rapid heartbeat, absent pulse, weak or irregular pulse, dizziness, 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 previously had hepatitis B, it may return)
• Intestinal bleeding (blood in the stool)
• During cancer treatment, and sometimes even without treatment, unusual levels of chemicals in the blood caused by the rapid breakdown of cancer cells (tumor lysis syndrome)

Frequency not known

• Widespread redness and peeling of the skin, which may be accompanied by itching or pain (generalized exfoliative dermatitis)

Reporting of adverse reactions

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of BRUKINSA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and vial following EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of BRUKINSA

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

Appearance of BRUKINSA and contents of the pack

BRUKINSA is a white or almost white hard capsule, marked with “ZANU 80” 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 Authorization Holder

BeOne Medicines Ireland Limited.

10 Earlsfort Terrace

Dublin 2

D02 T380

Ireland

Tel. +353 1 566 7660

E-mail [email protected]

Manufacturer responsible

BeOne Medicines I GmbH, Dutch Branch

Evert van de Beekstraat 1, 104

1118 CL Schiphol

Netherlands

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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