Acalabrutinib
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.Pregnancy: avoid
Avoid in pregnancy. May harm the fetus: a negative pregnancy test is needed before starting, contraception is used during treatment and for a short time after, and breastfeeding…
Second-generation covalent BTK inhibitor, more selective than ibrutinib, taken twice a day for CLL, small lymphocytic lymphoma and mantle cell lymphoma.
Quick facts
- Group
- Kinase inhibitors (targeted oncology)
- Target
- Bruton's tyrosine kinase (BTK)
- Used for
- Chronic lymphocytic leukaemia · Mantle cell lymphoma
- Key effects
- Headache · Diarrhoea · Joint and muscle pain
- Monitor
- Blood count · Signs of infection and bleeding
- ATC
- L01EL02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows acalabrutinib in the ATP site of the mouse BTK kinase domain, which is nearly identical to the human one.
B-cell cancers depend on signals from the B-cell receptor, which pass through Bruton's tyrosine kinase. Acalabrutinib binds covalently and irreversibly to a cysteine in the BTK active site, switching the kinase off for good; malignant B cells lose their growth and survival signals. It hits other kinases such as EGFR and ITK less than ibrutinib, which is meant to cause fewer off-target effects.
- Acalabrutinib binds a cysteine in BTK covalently
- B-cell receptor signals are cut off
- Malignant B cells stop growing and die
Indications
- Chronic lymphocytic leukaemia and small lymphocytic lymphoma. Chronic lymphocytic leukaemia →
- Mantle cell lymphoma. Non-Hodgkin lymphoma →
Adverse effects
Common
- Headache
- Diarrhoea, nausea, vomiting, constipation, abdominal pain
- Bruising and small red or purple spots
- Joint and muscle pain, tiredness, rash
Contraindications
- No absolute contraindications in the label apart from hypersensitivity; see the warnings
Key interactions
- Some prescription medicines and grapefruit
- Some must not be combined with acalabrutinib or change its levels; every new medicine is checked first.
What is monitored
- Blood count
- Signs of infection and bleeding
- Heart rhythm (palpitations, irregular pulse)
- Skin checks; hepatitis B history
Administration and safety
- Oral tablet every 12 hours, with or without food, at about the same times each day.
- Swallowed whole with water: not chewed, crushed, dissolved or cut.
- Hazardous drug: tablets are handled with care.
Pregnancy and breastfeeding
Avoid in pregnancy. May harm the fetus: a negative pregnancy test is needed before starting, contraception is used during treatment and for a short time after, and breastfeeding is paused.
Nursing care
- Ask about recent surgery, infections, hepatitis B, heart rhythm problems and bleeding disorders before starting.
- Teach to report fever, cough, palpitations, fainting, black stools or blood in the urine.
- Teach sun protection: protective clothing, sunglasses and sunscreen, because of skin cancer risk.
- Review any new medicine and grapefruit with the pharmacist.
Pharmacokinetics
- Absorption
- Oral, twice a day, with or without food.
- Metabolism
- Liver; some medicines and grapefruit change its levels.
- Half-life
- Short, about 1 hour (its active metabolite about 3.5 hours), yet BTK stays blocked because the binding is covalent.
Test yourself
Think of the answer, then tap the question to see it.
How does acalabrutinib bind BTK?
Covalently and irreversibly, to a cysteine in the active site.
How does acalabrutinib differ from ibrutinib?
It is more selective for BTK, with less effect on kinases such as EGFR and ITK.
Which skin advice is given to patients on acalabrutinib, and why?
Sun protection, because second cancers, especially skin cancers, are more common.
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: Acalabrutinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Structure of BTK kinase domain with the second-generation inhibitor acalabrutinib (RCSB Protein Data Bank, 2023).
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Representative model, for educational purposes only.