Key points
- Ibrutinib (Imbruvica) is a targeted tablet taken once a day that cuts off the growth signal in cancerous lymphocytes [1].
- It is used for chronic lymphocytic leukaemia (CLL) and a type of lymphoma called Waldenström macroglobulinaemia [1].
- In several large studies, it controlled the disease better than the treatments it was compared with [1, 3, 4, 5, 6].
- The main serious side effects: bleeding, an irregular heartbeat, high blood pressure and infection [1].
- It interacts with many medicines; do not eat grapefruit or Seville oranges, and give your doctor a list of your medicines [1].
What is this drug and how does it work?
For physicians
Ibrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK). It forms a covalent (irreversible) bond with a cysteine residue in the BTK active site and inhibits the enzyme's activity [1]. BTK is a signalling molecule in the B-cell receptor pathway needed for B-cell migration, adhesion and survival; in preclinical studies ibrutinib inhibited malignant B-cell proliferation and survival [1].
Ibrutinib was first approved in the United States in 2013 and comes as capsules, tablets and an oral suspension [1]. Besides cancer, it is also approved for chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy [1].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Previously treated CLL/SLL [1, 3]
- CLL/SLL with 17p deletion [1]
- Untreated CLL/SLL in patients aged 65 and over [1, 4]
- Untreated CLL in patients aged 65 and over [5]
- Untreated CLL/SLL in patients aged 70 and under [1, 6]
- Waldenström macroglobulinaemia [1, 7]
- Mantle cell lymphoma (MCL) [2, 8, 9]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting | Key evidence |
|---|---|---|
| Previously treated CLL/SLL | Monotherapy (FDA-approved use) | RESONATE [3]: vs ofatumumab, lower risk of progression (HR 0.22) and death (HR 0.43); overall response 42.6% vs 4.1% [1] |
| CLL/SLL with 17p deletion | Monotherapy (FDA-approved use) | 17p deletion subgroup in RESONATE: lower risk of progression (HR 0.25) [1] |
| Untreated CLL/SLL in patients aged 65 and over | Monotherapy (FDA-approved use) | RESONATE-2 [4]: vs chlorambucil, lower risk of progression (HR 0.16); overall response 82.4% vs 35.3% [1] |
| Untreated CLL in patients aged 65 and over | Ibrutinib alone or with rituximab vs bendamustine + rituximab | A041202: 2-year progression-free survival 87% with ibrutinib and 88% with ibrutinib + rituximab vs 74% with BR (HR 0.39 and 0.38); adding rituximab gave no further benefit [5] |
| Untreated CLL/SLL in patients aged 70 and under | With rituximab vs FCR (FDA-approved use) | E1912 [6]: lower risk of progression (HR 0.34) [1]; 3-year overall survival 98.8% vs 91.5% [6] |
| Waldenström macroglobulinaemia | Monotherapy or with rituximab (FDA-approved use) | iNNOVATE [7]: ibrutinib + rituximab vs placebo + rituximab, lower risk of progression (HR 0.25); response 76% vs 31% [1] |
| Mantle cell lymphoma (MCL) | Withdrawn in the United States; approved in the European Union | The FDA accelerated approval for relapsed MCL (2013) was withdrawn on 18 May 2023 [2]. The EMA has approved it for untreated MCL (transplant candidates) and relapsed or refractory MCL [8]. TRIANGLE: adding ibrutinib to induction and maintenance, 3-year failure-free survival 88% vs 72% (HR 0.52) [9] |
The RESONATE, RESONATE-2, E1912 and iNNOVATE figures come from the FDA label. HR: hazard ratio; a value below 1 means a lower risk of progression or death. The marginal zone lymphoma (MZL) indication was also withdrawn in the United States on the same date [2].
How it is taken and dosing
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- Ibrutinib is taken once a day at about the same time every day [1].
- Swallow the capsule or tablet whole with a glass of water; do not open, break or chew the capsule, and do not cut, crush or chew the tablet [1].
- Missed dose: take it as soon as possible on the same day and return to your normal schedule the next day; do not take an extra dose to make up [1].
- Treatment usually continues until the disease progresses or side effects cannot be tolerated [1]. Do not stop the drug or change the dose without talking to your doctor.
- If you are going to have surgery or dental work, tell your doctor; ibrutinib may need to be stopped for a few days before and after [1].
- In the first weeks of single-agent treatment, a rise in lymphocytes in blood tests is common (in about two in 3 patients); it usually starts in the first month and usually settles within about 3 months [1].
- Before starting: assess cardiac history and function; bilirubin and transaminases; assess the risk of tumour lysis syndrome (high tumour burden); check for anticoagulant or antiplatelet use (higher risk of major bleeding). In high-risk patients, consider standard prophylaxis against opportunistic infections (such as PJP) [1].
- Dose modification (after withholding until recovery to grade 1 or baseline): grade 2 heart failure: first occurrence 280, second 140 mg, third discontinue. Grade 3 arrhythmia: first occurrence 280 mg, second discontinue. Grade 3 to 4 heart failure or grade 4 arrhythmia: discontinue. Other grade 3 to 4 non-haematological toxicities, grade 3 to 4 neutropenia with infection or fever, grade 4 haematological toxicity: first occurrence 280, second 140 mg, third discontinue. Before resuming after a cardiac event, weigh benefit and risk [1]. Suspected drug-induced liver injury: withhold; confirmed: discontinue [1].
- CYP3A inhibitors: moderate inhibitor: 280 mg. Voriconazole 200 mg twice daily or posaconazole suspension 100 mg once or twice daily or 200 mg twice daily: 140 mg. Posaconazole suspension 200 mg three times daily or 400 mg twice daily, IV 300 mg or delayed-release tablets 300 mg once daily: 70 mg. Other strong inhibitors: avoid; for short-term use (e.g., anti-infectives for 7 days or less), interrupt ibrutinib. After the inhibitor is stopped, resume the previous dose. Avoid strong CYP3A inducers and grapefruit and Seville oranges [1].
- Liver and kidney: Child-Pugh A: 140 mg daily; Child-Pugh B: 70 mg daily; Child-Pugh C: avoid. Mild to moderate renal impairment (creatinine clearance above 25 mL/min) does not affect exposure; there are no data for severe impairment or dialysis [1].
- Surgery: consider withholding for at least 3 to 7 days before and after surgery depending on the type of surgery and bleeding risk [1].
- Monitoring: monthly CBC; blood pressure throughout treatment; cardiac rhythm and function (ECG or echocardiography with palpitations, light-headedness, syncope, chest pain or new dyspnoea); liver tests during treatment; fever and infection; second primary skin cancers [1].
For physicians
Standard dosing (FDA label)
CLL/SLL
Untreated or previously treated, including 17p deletionCycle length: Continuous
Untreated or previously treated, including 17p deletion [1]
Before prescribing: Prescribing notes: interactions, dose modification and monitoring| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Ibrutinib | 420 mg | Oral | Once daily, at about the same time every day |
| In combination | |||
| Rituximab or obinutuzumab, or bendamustine + rituximab (BR) | As per those drugs' labels | IV | On shared days, ibrutinib before the antibody |
Monotherapy or in combination [1].
Waldenström macroglobulinaemia
Monotherapy or with rituximabCycle length: Continuous
Monotherapy or with rituximab [1]
Before prescribing: Prescribing notes: interactions, dose modification and monitoring| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Ibrutinib | 420 mg | Oral | Once daily, at about the same time every day |
| In combination | |||
| Rituximab | As per that drug's label | IV | On shared days, ibrutinib before rituximab |
Plasmapheresis for hyperviscosity before and during treatment needs no dose change [1].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
For physicians
The most common adverse reactions (≥ 30%) in patients with B-cell malignancies are thrombocytopenia, diarrhoea, fatigue, musculoskeletal pain, neutropenia, rash, anaemia, bruising and nausea [1]. The table below shows the frequency of some adverse reactions in RESONATE-2 (untreated CLL/SLL in patients aged 65 and over) [1].
| Adverse reaction | Ibrutinib (135 patients) | Chlorambucil (132 patients) |
|---|---|---|
| Diarrhoea | 42% | 17% |
| Musculoskeletal pain | 36% | 20% |
| Fatigue | 30% | 38% |
| Cough | 22% | 15% |
| Nausea | 22% | 39% |
| Rash | 21% | 12% |
| Peripheral oedema | 19% | 9% |
| Bruising | 19% | 7% |
| Dry eye | 17% | 5% |
| Arthralgia | 16% | 7% |
| Skin infection | 15% | 3% |
| Pneumonia | 14% | 7% |
Hypertension was reported in 14% in RESONATE-2 (chlorambucil: 1%) and in 42% (grade ≥ 3 in 19%) in E1912 (ibrutinib + rituximab, longer treatment duration) [1].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Severe bleeding: black stools, vomiting blood or a severe headache; be sure to tell your doctor if you take a blood thinner or are going to have surgery [1].
- Heart rhythm problems: palpitations, dizziness, fainting or shortness of breath [1].
- High blood pressure, which becomes more common over the months; check your blood pressure regularly [1].
- Serious infection: fever, chills or cough [1].
- Liver damage (yellowing), a higher risk of skin cancer, and harm to an unborn baby [1].
For physicians
Ibrutinib has no boxed warning, but the FDA label lists these warnings [1]:
- Haemorrhage: major bleeding (such as intracranial or gastrointestinal haemorrhage) occurred in 4.2% and fatal bleeding in 0.4% of 2838 patients; bleeding of any kind including bruising in 39%. Concomitant anticoagulants or antiplatelet agents increase the risk of major bleeding (up to 6.1% with anticoagulants) [1].
- Cardiac arrhythmias, heart failure and sudden death: cardiac or sudden death in 1% of 4896 patients; grade ≥ 3 atrial fibrillation or flutter in 3.7%, grade ≥ 3 ventricular tachyarrhythmia in 0.2% and grade ≥ 3 heart failure in 1.3%, especially in patients with hypertension, diabetes, previous arrhythmia or acute infection [1].
- Hypertension: in 19% of patients (grade ≥ 3 in 8%), with a median time to onset of 5.9 months; its frequency rises over time [1].
- Infections: grade ≥ 3 infection in 21% of patients; PML and Pneumocystis pneumonia have also been reported [1].
- Cytopenias: with monotherapy, grade 3–4 neutropenia in 23%, grade 3–4 thrombocytopenia in 8% and grade 3–4 anaemia in 2.8% [1].
- Second primary malignancies in 10% (most often non-melanoma skin cancer in 6%), drug-induced liver injury, which can be severe or fatal, and tumour lysis syndrome [1].
In the ALPINE trial in relapsed CLL, zanubrutinib (a more selective BTK inhibitor) gave longer progression-free survival and fewer cardiac events than ibrutinib [10].
When should I call my doctor?
Call your doctor or go to the emergency department straight away if you have [1]:
- A severe headache, blood in the stool or urine (black or red stools), or prolonged or uncontrolled bleeding
- Palpitations, light-headedness, dizziness, fainting, shortness of breath, chest discomfort or swollen legs
- Fever, chills, weakness or confusion (signs of infection)
- Abdominal pain or discomfort, dark urine or yellow skin and eyes (possible liver damage)
- A possible or confirmed pregnancy
Interactions, pregnancy and precautions
- Other medicines: some medicines, such as antifungal drugs (ketoconazole, itraconazole, voriconazole, posaconazole), raise the level of ibrutinib in the blood and increase side effects; your doctor may lower the dose or pause it for a while. Medicines such as rifampicin (a tuberculosis drug) reduce its effect and should not be taken with it [1]. Tell your doctor about all prescription and over-the-counter medicines, vitamins and herbal remedies [1].
- Food: do not eat grapefruit, grapefruit juice or Seville oranges (or Seville orange marmalade) during treatment, because they raise the drug level in the blood [1].
- Anticoagulants and antiplatelet drugs: using them at the same time increases the risk of severe bleeding; your doctor should weigh the risks and benefits [1].
- Pregnancy and breastfeeding: ibrutinib can harm an unborn baby. Women who could become pregnant and men whose partner could become pregnant should use effective contraception during treatment and for 1 month after the last dose; do not breastfeed for 1 week after the last dose [1].
- Monitoring: a monthly full blood count, regular blood pressure checks and liver tests during treatment are recommended [1].
Frequently asked questions
Why shouldn't I eat grapefruit or Seville oranges?
These fruits raise the level of ibrutinib in the blood and increase side effects [1].
I bruise more easily; should I worry?
Should I stop the drug before surgery or a tooth extraction?
It may be needed. The FDA label advises your doctor to consider stopping ibrutinib for at least 3 to 7 days before and after surgery depending on the type of surgery and the bleeding risk [1]. Do not stop it on your own.
Why has my lymphocyte count gone up after starting the drug?
A rise in lymphocytes at the start of single-agent treatment is common (in about two in 3 patients), usually happens in the first month and usually settles within about 3 months [1]. Your doctor will interpret the results.
Is ibrutinib used for mantle cell lymphoma?
Key studies
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Key studies
5 itemsiwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
EHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation
Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL
Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
Related cancer types
References
10 referencesShow all references, 7 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1IMBRUVICA (ibrutinib) capsules, tablets and oral suspension — Prescribing Information
- 2
- 3
- 4
- 5
- 6
- 7Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia
- 8
- 9Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
- 10Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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