Brukinsa (Zanubrutinib): Uses, Dosage, Side Effects and Warnings

Brukinsa (zanubrutinib) is a once- or twice-daily pill that blocks Bruton’s tyrosine kinase (BTK), a signalling protein that cancerous B cells depend on to survive and grow.

• What it treats: five B-cell blood cancers in adults: chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), Waldenström’s macroglobulinemia, mantle cell lymphoma, marginal zone lymphoma and follicular lymphoma (with obinutuzumab).
• How you take it: 160 mg twice a day or 320 mg once a day, with or without food, until the cancer progresses or side effects become too much. It comes as 80 mg capsules and, since 2025, as a scored 160 mg tablet.
• Most common side effects: low neutrophil and platelet counts, upper respiratory infections, bleeding or bruising, muscle and joint pain, rash and diarrhea.
• Serious risks: major bleeding, serious infections, low blood counts, second cancers (mostly skin cancers), heart rhythm problems and liver injury.
• How it compares: in the head-to-head ALPINE trial in relapsed CLL, zanubrutinib beat the first BTK inhibitor, ibrutinib, on both response and progression-free survival, with fewer heart rhythm problems.

This is general information, not medical advice. Brukinsa is prescribed and monitored by hematologists and oncologists. Never change your dose or stop taking it without speaking to your cancer team.

Brukinsa at a glance

	Details
Generic name	Zanubrutinib
Drug class	Bruton’s tyrosine kinase (BTK) inhibitor, a kinase inhibitor
Made by	BeOne Medicines (formerly BeiGene)
First US approval	November 2019 (mantle cell lymphoma)
Forms	80 mg capsules; 160 mg scored film-coated tablets
Usual dose	160 mg twice daily or 320 mg once daily
Taken with food?	Either way; swallow whole with water
Contraindications	None listed in the US label
Key interactions	Strong and moderate CYP3A inhibitors (dose reduction); strong and moderate CYP3A inducers (avoid)
Pregnancy	Can harm a fetus; use effective contraception during treatment and for 1 week after the last dose

What is Brukinsa used for?

Brukinsa is approved by the US Food and Drug Administration (FDA) for adults with these B-cell cancers:

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): as a first treatment or after other treatments. CLL and SLL are the same disease; CLL mainly involves the blood and bone marrow, SLL mainly the lymph nodes.
• Waldenström’s macroglobulinemia (WM): a slow-growing lymphoma that makes large amounts of an antibody called IgM, which can thicken the blood.
• Mantle cell lymphoma (MCL): in people who have had at least one previous treatment.
• Marginal zone lymphoma (MZL): relapsed or refractory disease after at least one anti-CD20-based treatment.
• Follicular lymphoma (FL): relapsed or refractory disease after at least two previous lines of treatment, taken together with the antibody obinutuzumab (Gazyva).

The CLL/SLL and Waldenström’s approvals are full approvals based on survival-type outcomes. The mantle cell, marginal zone and follicular lymphoma approvals are accelerated approvals based on response rates and how long responses last, which means confirmatory trials are still required for those uses.

How Brukinsa works

Healthy and cancerous B cells both rely on a signalling chain called the B-cell receptor pathway. BTK is a key link in that chain. When it is switched on, it tells the cell to keep dividing, to stay alive and to stay put in the lymph nodes and bone marrow where it is protected.

Zanubrutinib binds permanently (covalently) to BTK and shuts it off. Cancer cells lose their survival signal, and many leave the lymph nodes for the bloodstream, where they eventually die. That is why people starting a BTK inhibitor often see their lymph nodes shrink while their white blood cell count temporarily rises. This “redistribution lymphocytosis” is expected and is not a sign the drug is failing.

Zanubrutinib was designed to be more selective for BTK than ibrutinib (Imbruvica), the first drug in the class. Ibrutinib also hits several “off-target” kinases, which is thought to explain some of its heart rhythm and bleeding problems. According to the FDA label, the approved dose keeps BTK 94% to 100% occupied in lymph nodes, around the clock.

How to take Brukinsa

• Dose: 160 mg twice a day or 320 mg once a day. Your doctor chooses which schedule; both give the same total daily dose.
• Capsules: 80 mg each, so the usual dose is two capsules twice a day or four once a day. Swallow them whole; do not open, break or chew them.
• Tablets: 160 mg each, so one tablet twice a day or two once a day. The tablets are scored, and the label allows splitting them in half when your prescriber tells you to.
• Food: take it with or without food, with a glass of water, at about the same time each day.
• Missed dose: take it as soon as you remember on the same day, then go back to your normal schedule. Do not take extra to make up.
• Severe liver impairment: the recommended dose is lower, 80 mg twice daily.
• Side effects: your doctor may pause treatment and restart at a lower dose (for example 80 mg twice daily) if you get significant side effects.

Treatment is usually continuous. Unlike chemotherapy, which is given in a fixed number of cycles, BTK inhibitors are normally taken every day for as long as they keep the cancer controlled and you tolerate them, which can be many years.

Brukinsa side effects

Across clinical trials, the most common side effects (in 30% or more of patients) were:

• low neutrophil count (42%)
• upper respiratory tract infection (39%)
• low platelet count (34%)
• bleeding of any kind (30%), most often bruising or small skin bleeds
• musculoskeletal pain (30%)

Other common effects include rash, diarrhea, cough, tiredness, constipation, pneumonia, urinary tract infection and high blood pressure. Many are mild. Your team will check your blood counts regularly, especially in the first months.

Serious risks and warnings

The FDA label lists six main warnings. None is a boxed warning, but each matters:

• Bleeding (hemorrhage): BTK inhibitors affect platelet function. Serious and sometimes fatal bleeding, including bleeding in the brain and gut, has occurred. The risk is higher if you also take blood thinners or antiplatelet drugs. Your doctor will usually pause Brukinsa for 3 to 7 days before and after surgery.
• Infections: serious bacterial, viral and fungal infections can happen, including pneumonia, shingles, hepatitis B reactivation and progressive multifocal leukoencephalopathy (PML), a rare brain infection. Your doctor may recommend preventive antivirals or antibiotics if you are at higher risk.
• Low blood counts (cytopenias): severe drops in neutrophils, platelets and red cells are possible, so complete blood counts are monitored during treatment.
• Second primary cancers: in trials, 13% of patients developed another cancer, most often non-melanoma skin cancer. Use sun protection and get regular skin checks.
• Heart rhythm problems: atrial fibrillation or flutter occurred in 3.7% of trial patients, and serious ventricular arrhythmias in 0.2%. The risk is higher if you already have heart disease, high blood pressure or an infection. Report palpitations, dizziness, fainting or chest discomfort.
• Liver injury: hepatotoxicity, including drug-induced liver injury, has been reported. Your team will check liver tests before and during treatment.

There is also embryo-fetal toxicity. Based on animal studies, zanubrutinib can harm an unborn baby. Women who could become pregnant should use effective contraception during treatment and for 1 week after the last dose. Men with a partner who could become pregnant should use effective contraception during treatment and for 1 week afterwards.

When to call your doctor straight away

• signs of bleeding: blood in urine or stool, black tarry stools, vomiting blood, coughing blood, severe headache, confusion or bruising you cannot explain
• fever, chills or other signs of infection
• a fast, pounding or irregular heartbeat, fainting or shortness of breath
• yellowing of the skin or eyes, dark urine or pain in the upper right abdomen

Drug interactions

Zanubrutinib is broken down mainly by the liver enzyme CYP3A. Drugs that block or speed up this enzyme change how much zanubrutinib reaches your blood.

Interacting drug type	Examples	What the label recommends
Strong CYP3A inhibitors	Clarithromycin (500 mg twice daily), itraconazole, voriconazole, posaconazole, ritonavir-boosted HIV drugs	Reduce to 80 mg once daily
Moderate CYP3A inhibitors	Erythromycin, fluconazole, diltiazem, verapamil	Reduce to 80 mg twice daily
Strong CYP3A inducers	Rifampin, carbamazepine, phenytoin, St John’s wort	Avoid
Moderate CYP3A inducers	Efavirenz, bosentan	Avoid if possible; dose adjustment may be advised
Blood thinners and antiplatelets	Warfarin, apixaban, rivaroxaban, aspirin, clopidogrel	Not forbidden, but bleeding risk rises; needs careful monitoring

Grapefruit and Seville oranges also inhibit CYP3A, so it is sensible to avoid them. Always tell every doctor, dentist and pharmacist that you take Brukinsa, including before any procedure.

Brukinsa vs ibrutinib and acalabrutinib

Three covalent BTK inhibitors are widely used: ibrutinib (Imbruvica), acalabrutinib (Calquence) and zanubrutinib (Brukinsa). A newer non-covalent one, pirtobrutinib (Jaypirca), is mainly used after a covalent BTK inhibitor stops working.

	Zanubrutinib (Brukinsa)	Ibrutinib (Imbruvica)	Acalabrutinib (Calquence)
Generation	Second	First	Second
Usual dosing	160 mg twice daily or 320 mg once daily	420 mg once daily (CLL)	100 mg twice daily
Head-to-head data vs ibrutinib	ALPINE: better response and progression-free survival in relapsed CLL	Reference drug	ELEVATE-RR: similar effectiveness, fewer heart problems
Atrial fibrillation	Lower than ibrutinib in trials	Highest of the three	Lower than ibrutinib in trials
Notable side effects	Low neutrophils, infections	Atrial fibrillation, high blood pressure, bleeding	Headache, especially early

In ALPINE, 652 people with relapsed or refractory CLL were randomly assigned to zanubrutinib or ibrutinib. The overall response rate was higher with zanubrutinib (80% vs 73% at the first analysis), and at about two years, progression-free survival was better too (78.4% vs 65.9%). Atrial fibrillation or flutter was less common with zanubrutinib (5.2% vs 13.3%). Those results, published in the New England Journal of Medicine in 2023, are the main reason zanubrutinib is now a preferred BTK inhibitor in many guidelines.

For untreated CLL, the SEQUOIA trial compared zanubrutinib with bendamustine plus rituximab chemoimmunotherapy in 479 patients without a 17p deletion, and zanubrutinib significantly improved progression-free survival.

Evidence in Waldenström’s macroglobulinemia

The ASPEN trial compared zanubrutinib with ibrutinib in people with Waldenström’s macroglobulinemia carrying the common MYD88 mutation. Its primary goal was to show a higher rate of very good partial or complete responses. Zanubrutinib had a numerically higher rate (28% vs 19%), but the difference did not reach statistical significance. The more consistent finding was tolerability: atrial fibrillation, high blood pressure, diarrhea and serious bleeding were less frequent with zanubrutinib, while low neutrophil counts were more frequent. ASPEN also enrolled a separate group of patients without the MYD88 mutation, who tend to respond less well to BTK inhibitors, and zanubrutinib still produced responses in many of them. The FDA approved Brukinsa for Waldenström’s in 2021 on the basis of this trial.

What happens if Brukinsa stops working

Over time, some cancers develop resistance, often through mutations in the BTK gene itself (most commonly at a site called C481) that stop covalent BTK inhibitors from binding. Options then include the non-covalent BTK inhibitor pirtobrutinib, the BCL-2 inhibitor venetoclax (often with an antibody), CAR T-cell therapy for some lymphomas, or clinical trials. Your hematologist may test for resistance mutations to guide the choice.

Which BTK inhibitor is best for a given person depends on their heart history, other medicines, bleeding risk, dosing preference and insurance coverage. There is no head-to-head trial of zanubrutinib versus acalabrutinib.

Who should be careful with Brukinsa

• People with heart disease, especially atrial fibrillation: zanubrutinib is less likely than ibrutinib to cause it, but monitoring is still important.
• People on blood thinners: the combination is possible but needs careful thought and monitoring.
• People with hepatitis B (past or present): the virus can reactivate; you will be tested before starting.
• People with liver disease: severe liver impairment needs a lower dose.
• Anyone planning surgery or dental work: a short break around the procedure is usually advised.
• Pregnancy and breastfeeding: avoid pregnancy; do not breastfeed during treatment and for 2 weeks after the last dose.

Living with Brukinsa: practical tips

• Keep a medication list and show it at every appointment, including over-the-counter drugs and supplements. Fish oil, vitamin E, turmeric and ginkgo can all add to bleeding risk.
• Protect your skin. Second skin cancers are the most common second cancer with BTK inhibitors. Use sunscreen and book an annual skin check.
• Stay up to date on vaccines, but avoid live vaccines. Response to vaccines may be weaker during treatment, so ask your team about timing.
• Track your blood pressure at home if you can. Hypertension is a recognised side effect of the class.
• Ask about cost support. Brukinsa is a specialty drug with a high list price. The manufacturer runs a patient support program, and foundations help with co-pays for blood cancers.

Frequently asked questions

What is Brukinsa used for?

Brukinsa (zanubrutinib) treats five B-cell blood cancers in adults: chronic lymphocytic leukemia or small lymphocytic lymphoma, Waldenström’s macroglobulinemia, mantle cell lymphoma after previous treatment, relapsed marginal zone lymphoma, and relapsed follicular lymphoma together with obinutuzumab.

Is Brukinsa a chemotherapy?

No. It is a targeted therapy, a kinase inhibitor that blocks one protein (BTK) that cancerous B cells depend on. It does not work like traditional chemotherapy, and it is usually taken continuously rather than in fixed cycles.

What are the most common side effects of Brukinsa?

The most common are low neutrophil and platelet counts, upper respiratory infections, bruising or other bleeding, and muscle and joint pain. Rash, diarrhea, cough and tiredness are also common.

Is Brukinsa better than Imbruvica?

In the ALPINE trial in relapsed CLL, zanubrutinib (Brukinsa) produced higher response rates and longer progression-free survival than ibrutinib (Imbruvica), with less atrial fibrillation. That does not make it the right choice for everyone; your hematologist weighs your heart history, other medicines and coverage.

Can I drink alcohol while taking Brukinsa?

There is no specific ban in the label, but alcohol can worsen bleeding risk, liver strain and low platelet counts. Keep it light and ask your cancer team what is safe for you.

How long do you take Brukinsa?

Usually until the cancer stops responding or side effects become unacceptable. For many people with CLL or Waldenström’s, that means years of daily treatment.

Should I stop Brukinsa before surgery?

Usually yes, for a short time. The label suggests considering a pause of 3 to 7 days before and after surgery, depending on the procedure and bleeding risk. Your hematologist and surgeon should agree on the plan.

References

• FDA. BRUKINSA (zanubrutinib) prescribing information, revised 6/2025
• FDA. BRUKINSA prescribing information, revised 1/2025 (Drugs@FDA)
• FDA. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma, 2023
• Brown JR, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia (ALPINE). N Engl J Med. 2023;388:319-332
• European Medicines Agency. Brukinsa product information
• Mayo Clinic. Zanubrutinib (oral route)