Zanubrutinib

Zanubrutinib is a targeted medicine that blocks a protein called BTK. This protein helps CLL cells to grow and multiply. Blocking it stops CLL cells from growing and dividing, leading to their death.

The brand name for zanubrutinib is Brukinska.

Zanubrutinib is suitable for adults. Your haematology team might recommend it for you if:

• You have CLL and have not had treatment before and:
• You have a genetic change in your CLL cells called 17p deletion or TP53 mutation or
• Other treatments are unsuitable for you.
• You have had treatment, but your CLL didn’t respond to it or came back after treatment. This is called refractory or relapsed CLL.

Before starting zanubrutinib, your haematology team will carry out checks to ensure it is suitable for you. These include:

• Blood tests to check your blood cell counts, kidney function and liver function
• Blood tests to check whether you have any infections that could flare up during treatment, such as viral hepatitis
• Checks of your heart health

Your team may recommend other tests, depending on your circumstances.

Your haematology team may ask if there is any possibility you might be pregnant. Zanubrutinib should not be taken during pregnancy.

Some medicines, supplements and food may interact with zanubrutinib. Or they may increase your risk of side effects. It is important to tell your haematology team about any medicines or supplements you are taking. This includes prescribed medicines and medicines you have bought yourself without a prescription. Examples include:

• Herbal medicines such as St John’s Wort
• Some blood thinners or medicines used to prevent blood clots, like warfarin
• Some medicines used to treat infections, including some antibiotics, antifungal and antiviral medicines
• Some medicines used to treat a rare sleep problem called narcolepsy
• Some medicines that lower your immune system
• Some medicines used to treat heart conditions and high blood pressure, including high blood pressure in your lungs
• Some medicines used to treat epilepsy
• Some medicines used to treat schizophrenia, severe depression or obsessivecompulsive disorder
• Some medicines used to treat cancer
• Some anti-sickness medicines that are used alongside chemotherapy
• Some opioid medicines that are used for pain relief
• Some medicines used to treat reflux or heartburn

Zanubrutinib capsules contain several ingredients. Tell your haematology team if you have any allergies or sensitivities.

Zanubrutinib comes as white, oval-shaped capsules that you take by mouth. You take zanubrutinib at home (or anywhere you are staying).

• Swallow your zanubrutinib capsules whole with a glass of water. You can take them with or without food.
• Do not open, break, or chew your capsules and do not dissolve them in water.
• Try to take your capsules at about the same time each day. If you take zanubrutinib twice a day, take it at the same time in the morning and evening.
• Avoid grapefruit or bitter oranges (Seville oranges), including the fruit, fruit juice, or foods or supplements containing them. This is because they affect how much zanubrutinib your body absorbs.
• Do not take supplements containing St John’s Wort, fish oil, vitamin E or flaxseed while taking zanubrutinib. This is because they affect how much zanubrutinib your body absorbs.

If you forget to take your capsules

If you forget to take your zanubrutinib:

• Skip the missed dose
• Take your next dose at the usual time

Zanubrutinib comes as capsules containing 80mg of zanubrutinib. The number of capsules you need to take should be printed on the medicine packaging. If you are not sure, ask your doctor or nurse.

Most adults with CLL take 320mg of zanubrutinib a day. You either take it as:

• Four capsules once a day or
• Two capsules twice a day. You usually leave around 12 hours between each dose.

You can store zanubrutinib at room temperature. Keep it safe where children cannot see or reach it.

Do not stop taking zanubrutinib without discussing it with your haematology team.

Most people carry on taking zanubrutinib for as long as it is working. Your haematology team may suggest stopping zanubrutinib and trying a different treatment if:

• It is not working well
• It stops working
• You are having side effects that are difficult to cope with
• Check-ups show it is affecting other parts of your body, like your heart, liver or kidneys
• You become pregnant

Your haematology team will check how well zanubrutinib is working and how well your body is coping with it.

• You’ll have regular blood tests to check your blood cell counts.
• You’ll also have occasional blood tests to check how well your liver and kidneys are working.
• You’ll have regular blood pressure checks. Your team may ask you to take your blood pressure at home and keep a record of it.
• Your doctor or nurse will examine you to check for signs and symptoms of:
  • Bleeding.
  • Infection.
  • Heart problems.
  • A rare reaction called tumour lysis syndrome.
  • Changes in your skin.
• If needed, you may have other examinations and scans to check the size of your lymph nodes and organs, like your spleen.

There are some precautions to be aware of when you are taking zanubrutinib.

• If you need surgery or to have a tooth out, you may need to stop zanubrutinib for 3 to 7 days before and after. This is to reduce your risk of bleeding. Your doctor will tell you exactly when to stop taking zanubrutinib and when to start it again.
• Zanubrutinib can make you vulnerable to serious infections. You might need to take medicines to prevent infections while taking zanubrutinib.
• You should avoid eating grapefruit and starfruit (carambola), including the fruit, fruit juice, or foods or supplements containing them.
• You should avoid eating bitter oranges (Seville oranges), including the fruit, bitter orange juice or food made with bitter oranges, like marmalade.
• You should avoid supplements such as fish oil, flaxseed, or vitamin E preparations.
• Zanubrutinib might make you very tired, low in energy, or dizzy. This might affect your ability to drive or operate machinery.
• Other medicines might interact with zanubrutinib. Your haematology team will tell you whether or how to take other medicines while you are on zanubrutinib.
• If you’ve had viral hepatitis in the past, it might flare up during zanubrutinib treatment. You’ll have a blood test before you start treatment. If this shows you’ve had viral hepatitis, your team will monitor you for flare-ups. You might be referred to a liver specialist for treatment.

We do not know what effect zanubrutinib has on fertility or pregnancy. Based on animal studies, it may damage sperm, increase pregnancy loss, and harm unborn babies.

• If you could get pregnant, it’s important to use effective contraception while you are taking zanubrutinib and for 1 month after stopping treatment.
• We do not know whether zanubrutinib affects the way hormonal contraceptives work. So, you need to use a barrier method like a condom, diaphragm or cap.
• If you’re taking zanubrutinib and you think you might be pregnant, tell your haematology team as soon as possible.
• If you’re planning to get pregnant or to make someone pregnant in the future, talk to your haematology team before starting treatment. They will talk to you about your treatment options.

Breastfeeding

We do not know if zanubrutinib passes into breastmilk or what effect it might have on breastfed babies or children.

You may get some side effects while you are taking zanubrutinib. Some people have very few side effects, whereas others get more serious side effects. They may differ from day to day.

Your haematology team should tell you what side effects to look out for and who to contact if you need to.

This is not a full list of all the side effects that can happen. The patient information leaflet in your medicine package has more information. Or you can find the leaflet in the Electronic Medicines Compendium.

Here, we list some of the more common side effects of zanubrutinib. These affect at least 1 in every 100 people who take zanubrutinib.

• Infections. Contact your team straight away if you think you have an infection. Look out for:
  • A high temperature (38°C or higher)
  • Shivering, chills or sweating
  • Sore throat, sneezing, blocked or runny nose or earache
  • Cough, chest pain or shortness of breath
  • Burning or stinging when you pee, or peeing more often than usual
  • Sickness or diarrhoea
  • Cold sores, or ulcers or blisters around your mouth or genitals
• Unexpected or unusual bruising or bleeding, like nosebleeds, bleeding gums or heavy periods. Look out for blood in your poo or pee, or red or purple spots under your skin. This may look different in black or brown skin. Tell your team if you notice any of these.
• Tummy problems. You might get diarrhoea, constipation, or tummy ache. You might feel sick or be sick. If you have these side effects, your team can give you medicines to help.
• Muscle, bone or joint pain. Talk to your team if this becomes troublesome.
• Changes to your skin. You might get a rash. This might look different on black or brown skin.
• Fatigue. You might experience extreme tiredness or lack of energy.
• Dizziness. You might feel lightheaded.
• Swelling. You might have swelling of your feet, ankles or hands.
• Heart problems. Contact your doctor if you get a fast or irregular heartbeat or a heart flutter. They will check your heart function.

There might be some side effects that your haematology team find during regular checks and blood tests. These include:

• Low levels of white blood cells called neutrophils (neutropenia). This makes you more vulnerable to infections. You might need treatment to prevent or treat infections.
• Low levels of red blood cells (anaemia).
• Low levels of platelets (thrombocytopenia). This can cause unusual bruising and bleeding because platelets help your blood to clot. You might need to have a transfusion.
• High blood pressure. If this happens, you might need to take blood pressure medicines.
• High levels of white blood cells. This might happen when you first start zanubrutinib. Your white blood cells may go up before they come down again. It doesn’t mean your CLL is getting worse.

Rarely, zanubrutinib might cause a side effect called tumour lysis syndrome.

This is a serious side effect of some cancer treatments. It happens if a large number of cancer cells die quickly and release chemicals into your bloodstream.

This affects fewer than 1 in every 100 people taking zanubrutinib. So, it does not happen to more than 99 in every 100 people. However, if it does happen, it can be serious, so it’s sensible to know what to look out for.

If zanubrutinib is not working well for you, your doctor will discuss your options with you. They might suggest changing your dose, pausing or stopping treatment.

They will talk to you about other treatment options that might be suitable for you.