Ibrutinib (Imbruvica), acalabrutinib (Calquence) and zanubrutinib (Brukinsa) are tablets or capsules used for chronic lymphocytic leukaemia (CLL) and some lymphomas. They all block a protein called BTK, so they are known as BTK inhibitors. They share many features, but there are practical differences in dosing, side effects and interactions. This guide sets them out.
How BTK inhibitors work
BTK is a tyrosine kinase, one of the enzymes that send growth signals inside cells. Blocking these signals stops the cells growing and dividing. This is a form of targeted therapy, not chemotherapy5. In the US, ibrutinib and acalabrutinib are licensed for CLL and small lymphocytic lymphoma, and both are also used for other conditions13. BTK inhibitors are among the main options for CLL that comes back or stops responding6.
Dosing and how you take them
| Ibrutinib | Acalabrutinib | Zanubrutinib | |
|---|---|---|---|
| Usual dose for CLL | 420 mg once a day1 | 100 mg about every 12 hours3 | 160 mg twice a day or 320 mg once a day4 |
| Food | Take with a glass of water1 | With or without food3 | With or without food4 |
| Swallowing | Do not open, break or chew capsules, or cut, crush or chew tablets1 | Swallow tablets whole; do not chew, crush, dissolve or cut3 | Do not open, break or chew capsules; tablets can be split only if prescribed4 |
If you miss a dose of ibrutinib, take it as soon as you can on the same day and go back to your usual schedule the next day. Do not take extra doses to make up1.
Side effects compared
- Ibrutinib: the most common side effects are low platelets, diarrhoea, tiredness, muscle and bone pain, low white cells, rash, anaemia, bruising and nausea1.
- Acalabrutinib: the most common are colds and other upper airway infections, diarrhoea, headache and muscle and bone pain3.
- Zanubrutinib: the most common are low white cells and platelets, upper airway infections, bleeding and muscle and bone pain4.
Heart rhythm, blood pressure and bleeding
These are the side effects people most often ask about:
- Heart rhythm. All three labels warn about irregular heart rhythms, including atrial fibrillation134. The ibrutinib label also warns about heart failure and sudden death, and says people with existing heart problems may be at greater risk1. Report palpitations, dizziness, fainting, breathlessness or chest discomfort.
- Blood pressure. High blood pressure is a listed warning for ibrutinib, and blood pressure should be checked during treatment1.
- Bleeding. All three can increase bleeding, including serious bleeding134. Tell your team if you take blood thinners or anti-platelet medicines, and report unusual bruising, blood in your urine or stools, or a severe headache.
All three also carry warnings about infections, low blood counts, other cancers (including skin cancers, so sun protection is advised) and liver problems134.
Surgery and dental work
Because of the bleeding risk, your doctor may pause the medicine for 3 to 7 days before and after surgery, depending on the type of procedure134. Always tell your surgeon or dentist that you take a BTK inhibitor, and do not stop it without your cancer team’s advice.
Interactions
- Grapefruit and Seville oranges should be avoided with ibrutinib1.
- Some antibiotics, antifungals and other medicines that block or speed up the CYP3A liver enzyme can change the levels of these medicines, and doses may need to change13.
- Acid-reducing medicines with acalabrutinib capsules. The capsule label says to avoid omeprazole-type medicines (PPIs), take the capsule 2 hours before an H2 blocker, and keep antacids at least 2 hours apart2. Check with your pharmacist which form you have.
Give your team a full list of what you take, including over-the-counter medicines and supplements. See our guide to taking cancer tablets at home.
Continuous treatment or a fixed course?
On their own, BTK inhibitors are usually taken for as long as they keep CLL under control and the side effects are manageable1. Another approach combines a BTK inhibitor with venetoclax for a set time. For example, acalabrutinib is licensed with venetoclax (with or without obinutuzumab) for a fixed course of 14 cycles of 28 days3. Your specialist can explain which approach suits you. See our guide to venetoclax in CLL.
If it stops working
If CLL comes back or stops responding, options can include a different BTK inhibitor, venetoclax, other targeted drugs, chemotherapy, and for some people a stem cell transplant or a clinical trial6. See our guide to when a cancer medicine stops working.
Generic versions and cost
Our generic Imbruvica and generic Venclexta pages explain the options, and our guide to what Imbruvica costs compares prices. We stock acalabrutinib, including Calquence 100 mg capsules and Acalnib 100 mg capsules. See all options on our ibrutinib and acalabrutinib pages, or browse our blood cancer medicines. All need a prescription.
Frequently asked questions
Does ibrutinib cause bleeding?
It can. Bleeding, including serious bleeding, is a known risk with ibrutinib and the other BTK inhibitors. Tell your team about any blood thinners you take, and report unusual bruising or bleeding.
Is acalabrutinib better than ibrutinib?
Neither is better for everyone. They differ in dosing, side effects and interactions, so your specialist will choose based on your health, especially your heart health, and your other medicines.
Can ibrutinib be crushed?
No. Do not open, break or chew ibrutinib capsules, or cut, crush or chew the tablets. Tell your team if you have trouble swallowing.
Do I need to stop ibrutinib before surgery?
Often, yes. Doctors may pause it for 3 to 7 days before and after surgery, depending on the procedure. Only stop it on your cancer team’s advice.
Can I take omeprazole with acalabrutinib?
The capsule label says to avoid omeprazole-type medicines (PPIs). Ask your pharmacist about other options and about the form of acalabrutinib you have.
Sources & references
- US National Library of Medicine, DailyMed. Imbruvica (ibrutinib) prescribing information.
- US National Library of Medicine, DailyMed. Calquence (acalabrutinib) capsules prescribing information.
- US National Library of Medicine, DailyMed. Calquence (acalabrutinib) tablets prescribing information.
- US National Library of Medicine, DailyMed. Brukinsa (zanubrutinib) prescribing information.
- Cancer Research UK. Ibrutinib (Imbruvica). Last reviewed 2 February 2024.
- National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ), Patient Version. Updated 15 October 2024.
Related reading
This content is for informational purposes only and is not medical advice. Do not stop or change a BTK inhibitor without your cancer team’s advice. Used as prescribed by a licensed medical professional.
Babu S. Shetty is a licensed clinical pharmacist with 14 years of experience. He holds a B.Pharm and M.Pharm from Mohan Kumaramangalam Medical College. At OnlineMeds, he reviews medicine and health content to help ensure it is accurate, evidence-based, and easy to understand.