Ibrutinib
Kinase inhibitors (targeted oncology)
Kinase inhibitors (targeted oncology)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Oral covalent BTK inhibitor that switches off B-cell receptor signalling in CLL and Waldenström macroglobulinaemia; watch bleeding and atrial fibrillation.
Quick facts
- Group
- Kinase inhibitors (targeted oncology)
- Target
- Bruton tyrosine kinase (BTK)
- Used for
- Chronic lymphocytic leukaemia
- Key effects
- Diarrhoea · Bruising and minor bleeding · Rash
- Monitor
- Blood counts · Pulse rhythm and blood pressure
- ATC
- L01EL01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows ibrutinib in the ATP site of the human BTK kinase domain, next to cysteine 481, the residue it bonds covalently.
Malignant B cells in CLL and related lymphomas depend on signals from the B-cell receptor, which pass through Bruton tyrosine kinase. Ibrutinib binds covalently to cysteine 481 near the ATP site and permanently inactivates BTK. B-cell receptor signalling fails, so the malignant B cells stop proliferating and die.
- B-cell receptor signals run through BTK
- Ibrutinib bonds covalently to BTK cysteine 481
- BTK is permanently switched off
- Malignant B cells stop proliferating and die
Indications
- Chronic lymphocytic leukaemia and small lymphocytic lymphoma. Chronic lymphocytic leukaemia →
- Waldenström macroglobulinaemia. MGUS and Waldenström macroglobulinaemia →
- Chronic graft-versus-host disease after failure of other systemic treatment.
Adverse effects
Common
- Diarrhoea, nausea
- Bruising and minor bleeding
- Musculoskeletal pain
- Rash
- Fatigue, fever
- Neutropenia, thrombocytopenia, anaemia
Contraindications
- No absolute contraindications; caution with anticoagulants, bleeding disorders, arrhythmia and severe liver impairment
Key interactions
- Strong CYP3A inhibitors (azoles, clarithromycin, grapefruit, Seville orange)
- Raise ibrutinib levels and toxicity.
- CYP3A inducers (rifampicin, St John's wort)
- Lower its levels; avoided.
- Anticoagulants and antiplatelet drugs
- Add to the bleeding risk.
- Surgery
- Usually held for several days before and after surgery because of bleeding risk.
What is monitored
- Blood counts
- Pulse rhythm and blood pressure; ECG if palpitations
- Signs of bleeding
- Signs of infection
Administration and safety
- Oral; swallowed whole at about the same time each day.
- Check the name carefully: kinase inhibitors with similar «-tinib» names are not interchangeable.
- Grapefruit and Seville oranges are avoided; plenty of fluids are encouraged.
Pregnancy and breastfeeding
Can harm the fetus; women and men with female partners use contraception during treatment and for a month after.
Nursing care
- Check pulse for irregularity and blood pressure at each visit.
- Review the medicine list for anticoagulants, antiplatelets and CYP3A interactions.
- Remind the team that ibrutinib is held around surgery and procedures.
- Teaching: report palpitations, dizziness, black stools, blood in urine, severe headache or fever.
Pharmacokinetics
- Absorption
- Oral; food increases absorption.
- Metabolism
- Liver, mainly CYP3A; liver impairment raises exposure.
- Elimination
- Metabolites mainly in the faeces.
- Half-life
- Short, about 4 to 6 hours, but BTK stays inhibited because the bond is covalent.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme does ibrutinib inhibit, and how?
Bruton tyrosine kinase, by a covalent bond to cysteine 481.
Which arrhythmia is typical of ibrutinib?
Atrial fibrillation.
Why is grapefruit avoided with ibrutinib?
It inhibits CYP3A and raises ibrutinib levels.
Connections
← Back to the class: Kinase inhibitors (targeted oncology)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Ibrutinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.