[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Kinase inhibitors (targeted oncology)](https://durgical.com/en/pharmacology/classes/kinase-inhibitors/) › Ponatinib

# 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[Kinase inhibitors (targeted oncology)](https://durgical.com/en/pharmacology/classes/kinase-inhibitors/)

**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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**BCR-ABL tyrosine kinase (ABL1 kinase domain), including the T315I gatekeeper mutant**Ponatinib

ⓘ 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.

**Target in 3D:** BCR-ABL tyrosine kinase (ABL1 kinase domain), including the T315I gatekeeper mutant. PDB structure 3OXZ (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3OXZ) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/chronic-myeloid-leukaemia/)
- Certain types of Philadelphia chromosome-positive acute lymphoblastic leukaemia. [Acute leukaemia (AML and ALL) →](https://durgical.com/en/conditions/acute-leukaemia/)

## Adverse effects

### Common

- Rash and dry skin
- High blood pressure
- Abdominal pain, constipation, diarrhoea
- Headache; bone, joint and muscle pain
- Raised lipase and amylase

### Serious (rare, important)

- Arterial occlusion and venous clots: heart attack, stroke, limb ischaemia, which can be fatal
- Heart failure and arrhythmias
- Liver toxicity, including liver failure
- Pancreatitis
- Bleeding, poor wound healing, eye problems and myelosuppression

## 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.

## Memory aid

PONAtinib PASSES the gatekeeper (T315I) — but it also hits the vessels: watch for clots in the arteries.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/ponatinib/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High alert**
An error with this medicine can cause serious harm: double checks and protocols are used.

## Connections

## Related drugs 4

- [Imatinib](https://durgical.com/en/pharmacology/imatinib/)
- [Dasatinib](https://durgical.com/en/pharmacology/dasatinib/)
- [Nilotinib](https://durgical.com/en/pharmacology/nilotinib/)
- [Bosutinib](https://durgical.com/en/pharmacology/bosutinib/)

## Related conditions 2

- [Chronic myeloid leukaemia](https://durgical.com/en/conditions/chronic-myeloid-leukaemia/)
- [Acute leukaemia (AML and ALL)](https://durgical.com/en/conditions/acute-leukaemia/)

[← Back to the class: Kinase inhibitors (targeted oncology)](https://durgical.com/en/pharmacology/classes/kinase-inhibitors/)

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](https://medlineplus.gov/druginfo/meds/a613029.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01EA05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [Crystal structure of ABL kinase domain bound with a DFG-out inhibitor AP24534](https://www.rcsb.org/structure/3OXZ) (RCSB Protein Data Bank, 2010).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/ponatinib/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/ponatinib/