Ponatinib
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.
Third-generation BCR-ABL inhibitor that also blocks the T315I mutant. Reserved for resistant CML and Ph-positive ALL because of arterial clots and liver damage.
Quick facts
- Group
- Kinase inhibitors (targeted oncology)
- Target
- BCR-ABL tyrosine kinase (ABL1 kinase domain), including the T315I gatekeeper mutant
- Used for
- Chronic myeloid leukaemia resistant · Certain types
- Key effects
- Rash and dry skin · High blood pressure · Headache
- Monitor
- Blood pressure at every visit · Liver tests
- ATC
- L01EA05
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows ponatinib (code name AP24534) in the inactive, DFG-out ABL kinase domain from mouse, which is nearly identical to the human kinase.
Ponatinib binds the ATP pocket of the BCR-ABL kinase in its inactive form. It still binds when the 'gatekeeper' threonine 315 is replaced by isoleucine (T315I), the mutation that defeats imatinib, dasatinib, nilotinib and bosutinib, and it inhibits native BCR-ABL and all known single resistant mutants. It also blocks other kinases such as VEGFR, PDGFR, FGFR and SRC, which helps explain its effects on blood vessels.
- Ponatinib binds the inactive BCR-ABL kinase
- It fits even with the T315I gatekeeper mutation
- Leukaemic signalling stops; VEGFR and other kinases are hit too
Indications
- Chronic myeloid leukaemia resistant or intolerant to earlier kinase inhibitors, or with the T315I mutation. Chronic myeloid leukaemia →
- Certain types of Philadelphia chromosome-positive acute lymphoblastic leukaemia. Acute leukaemia (AML and ALL) →
Adverse effects
Common
- Rash and dry skin
- High blood pressure
- Abdominal pain, constipation, diarrhoea
- Headache; bone, joint and muscle pain
- Raised lipase and amylase
Contraindications
- Not stated; used with great caution after a recent arterial clot, heart attack or stroke
Key interactions
- Strong CYP3A inhibitors and grapefruit
- Raise ponatinib levels; grapefruit is avoided.
- St John's wort and other CYP3A inducers
- Lower ponatinib levels.
- Drugs that reduce stomach acid (e.g., proton pump inhibitors)
- May reduce absorption.
What is monitored
- Blood pressure at every visit
- Signs of arterial or venous clots and heart failure
- Liver tests, lipase and blood count
- Eye examination if vision changes
Administration and safety
- Oral tablet once a day, with or without food, at about the same time.
- Hazardous drug: tablets are handled with care.
Pregnancy and breastfeeding
A pregnancy test may be done before starting; contraception is used during treatment and breastfeeding is stopped during treatment and for a short time after. It may lower female fertility.
Nursing care
- Ask about previous clots, stroke, heart attack, high blood pressure, high cholesterol, diabetes and heart disease before starting.
- Teach the warning signs of a clot or stroke: chest pain, one-sided weakness, trouble speaking, sudden severe headache, a cold or painful limb.
- Teach to report yellow skin, dark urine, upper-right or back-radiating abdominal pain.
- Avoid grapefruit and St John's wort; review acid-reducing medicines.
Pharmacokinetics
- Absorption
- Oral tablet, with or without food; drugs that raise gastric pH may lower absorption.
- Metabolism
- Mainly CYP3A4, plus CYP2C8, CYP2D6 and esterases; CYP3A inhibitors raise its levels.
- Elimination
- Mostly in the faeces.
- Half-life
- About 24 hours.
Test yourself
Think of the answer, then tap the question to see it.
Which BCR-ABL mutation does ponatinib inhibit that other kinase inhibitors do not?
The T315I gatekeeper mutation.
What is the most feared toxicity of ponatinib?
Arterial occlusion (heart attack, stroke, limb ischaemia) and venous clots.
Which vital sign is checked at every visit on ponatinib?
Blood pressure, because it often rises.
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: Ponatinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Crystal structure of ABL kinase domain bound with a DFG-out inhibitor AP24534 (RCSB Protein Data Bank, 2010).
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Representative model, for educational purposes only.