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Ponatinib oral


Oral formulations of ponatinib (as hydrochloride).

Drugs List

  • ICLUSIG 15mg tablets
  • ICLUSIG 30mg tablets
  • ICLUSIG 45mg tablets
  • ponatinib 15mg tablets
  • ponatinib 30mg tablets
  • ponatinib 45mg tablets
  • Therapeutic Indications


    Chronic, accelerated or blast phase chronic myeloid leukaemia
    Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia

    Treatment of chronic, accelerated or blast phase chronic myeloid leukaemia (CML) with resistance or intolerance to dasatinib or nilotinib and for treatment of patients where subsequent treatment with imatinib is not clinically appropriate or who have the T315I mutation.

    Treatment of Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) with resistance or intolerance to dasatinib and for treatment of patients where subsequent treatment with imatinib is not clinically appropriate or who have the T315I mutation.


    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.


    45mg of ponatinib once daily.

    Dose adjustment may be necessary for the management of treatment toxicity or to reduce the risk of arterial occlusion. A dose reduction to 15mg should also be considered for chronic phase CML patients who have achieved a major cytogenetic response.
    If a dose reduction is considered the following factors should be taken into account: cardiovascular risk, side effects, time to cytogenetic response and BCR-ABL transcript levels.

    Additional Dosage Information

    Dose adjustments in myelosuppression
    Absolute neutrophil count (ANC) less than 1 x 10 to the power of 9/L or Platelets less than 50 x 10 to the power of 9/L
    In each case withhold until recovery to ANC equal to or greater than 1.5 x 10 to the power of 9/L and platelets equal to or greater than 75 x 10 to the power of 9/L, then dose as follows.
    Occurrence at initial dose: Resume at same dose.
    Occurrence at 45mg: Resume at 30mg.
    Occurrence at 30mg: Resume at 15mg.

    Arterial occlusion and venous thromboembolism
    Interrupt treatment. Assess the benefit of treatment against the risk to the patient before resuming treatment following resolution of event.

    Dose adjustments in non-haematological toxicity
    Grade 2 pancreatitis and/or asymptomatic elevation of lipase/amylase
    Continue at the same dose.

    Grade 3 or 4 asymptomatic elevation of lipase/amylase (greater than 2 times institution upper limit of normal (IULN)) only
    In each case withhold until recovery to less than or equal to Grade 1 (less than 1.5 times IULN)
    Occurrence at 45mg: Resume at 30mg.
    Occurrence at 30mg: Resume at 15mg.
    Occurrence at 15mg: Consider discontinuing.

    Grade 3 pancreatitis
    In each case withhold until recovery to less than or equal to grade 2 pancreatitis and reduce dose as follows.
    Occurrence at 45mg: Resume at 30mg.
    Occurrence at 30mg: Resume at 15mg.
    Occurrence at 15mg: Consider discontinuing.

    Grade 4 pancreatitis

    Dose adjustments for hepatic toxicity
    Elevation of liver transaminase greater than 3 times upper limit of normal (ULN), persistent grade 2 (longer than 7 days), Grade 3 or higher
    In each case withhold until recovery to less than or equal to Grade 1 (less than 3 times ULN) or pre-treatment grade
    Occurrence at 45mg: Resume at 30mg.
    Occurrence at 30mg: Resume at 15mg.
    Occurrence at 15mg: Discontinue.

    Elevation of AST or ALT (equal to or greater than 3 times ULN) with concurrent elevation of bilirubin (greater than 2 times ULN) and alkaline phosphatase less than 2 times ULN

    Concurrent use of potent cytochrome P450 3A4 inhibitors
    Consider reducing initial dose to 30mg once daily with concomitant use of potent inhibitors of cytochrome P450 3A4 (e.g. clarithromycin, itraconazole, ketoconazole, ritonavir, saquinavir, telithromycin, or voriconazole).


    Children under 18 years
    Uncontrolled hypertension

    Precautions and Warnings

    Neutrophil count below 1.0 x 10 to the power of 9 / L
    Patients over 65 years
    Platelet count below 50 x 10 to the power of 9 / L
    Tobacco smoking
    Behcet's disease
    Cerebrovascular disorder
    Diabetes mellitus
    End stage renal disease
    Giant cell arteritis
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    History of alcohol abuse
    History of aneurysm
    History of cerebrovascular accident
    History of hepatitis B
    History of ischaemic heart disease
    History of myocardial infarction
    History of pancreatitis
    Ischaemic heart disease
    Lactose intolerance
    Marfan syndrome
    Occlusive peripheral arterial disease
    Renal impairment - creatinine clearance below 50ml/minute
    Takayasu arteritis
    Vascular Ehlers-Danlos syndrome

    Advise ability to drive/operate machinery may be affected by side effects
    Before initiating screen all patients for hepatitis B infection
    Ensure hypertension is controlled prior to treatment
    Evaluate patients for cardiovascular disease prior to treatment
    Hepatitis B: Refer prior to initiation to liver disease specialist
    Treatment to be initiated and supervised by a specialist
    Contains lactose
    Consult local policy on the safe use of oral anti-cancer drugs
    Staff: Not to be handled by pregnant staff
    Monitor cardiac function before and regularly during treatment
    Monitor hepatic function before treatment and regularly during treatment
    Discontinue if AST/ALT > 3x ULN & bilirubin > 2x ULN & ALKP < 2x ULN
    If visual disturbances occur, perform ophthalmic evaluation
    Monitor blood counts every 2 weeks for first 3 months then monthly
    Monitor blood pressure
    Monitor patients at risk for signs & symptoms of venous thromboembolism
    Monitor serum lipase every 2 weeks for first 2 months then periodically
    Advise patient to report headaches, seizures, confusion, visual disturbance
    Advise patient to report mucosal/skin reactions (blistering or peeling)
    Advise patients to report symptoms of acute pancreatitis immediately
    Consider discontinuing therapy if significant cardiac failure develops
    Consider pancreatitis in patients with unexplained abdominal pain
    Reactivation of hepatitis B may occur in chronic carriers
    Suspend treatment and/or reduce dose for persistent grade 2 hepatotoxicity
    Suspend treatment if transaminases >3 times upper limit of normal
    Consider reducing or interrupting treatment if lipase levels are elevated
    Discontinue if an adequate response not achieved within 3 months
    Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
    Discontinue treatment if grade 4 pancreatitis occurs
    Suspend if venous thromboembolism develops
    Suspend therapy &/or reduce dose if neutrophil count <1 x 10 to power 9/L
    Suspend therapy &/or reduce dose if platelets below 50 x 10 to power 9/L
    Suspend treatment and/or reduce dose if grade 3 or higher hepatotoxicity
    Suspend treatment and/or reduce dose if grade 3 pancreatitis occurs
    Suspend treatment if arterial or venous occlusion suspected
    Suspend treatment if elevated serum lipase plus abdominal pain
    Suspend treatment if grade 3 or greater elevations in lipase or amylase
    Suspend treatment if hypertension cannot be controlled
    Suspend treatment if bleeding requiring medical treatment occurs
    Advise patient not to take St John's wort concurrently
    Advise patient grapefruit products may increase plasma level
    Female: Barrier or non-hormonal contraception required during treatment
    Male & female: Ensure adequate contraception during treatment
    Advise patient on giving up smoking

    Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. Interrupt treatment if PRES is diagnosed and only resume once it has resolved and the benefit of treatment outweigh the risks.

    Cardiovascular status of the patient should be assessed, and cardiovascular risk factors should be actively managed before starting treatment. Cardiovascular status should continue to be monitored and optimised during treatment.

    Serious haemorrhage events have been reported in patients taking ponatinib, the most common being cerebral and gastrointestinal haemorrhage. The majority of bleeding events occurred in patients with grade 3/4 thrombocytopenia. Suspend treatment in patients with severe haemorrhage and evaluate.

    Haematologic support such as platelet transfusion and haematopoietic growth factors can be used during treatment when clinically indicated.

    Risk factors for aneurysm and artery dissection
    Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.

    Pregnancy and Lactation


    Ponatinib is contraindicated during pregnancy.

    The manufacturer suggests ponatinib must only be used during pregnancy when deemed essential and if used the patient must be informed of the potential risk to the foetus. At the time of writing, there are no adequate data from the use of ponatinib in pregnant women. Studies in animals have shown reproductive toxicity, including soft tissue and skeletal alterations at non-toxic maternal doses, and post-implantation loss at toxic levels.

    The effect of concurrent therapies must also be considered.


    Ponatinib is contraindicated during breastfeeding.

    The manufacturer advises stopping breastfeeding during treatment.
    It is not known if ponatinib is excreted in human breast milk. A risk to neonates cannot be excluded.

    Side Effects

    Abdominal discomfort
    Abdominal distension
    Angina pectoris
    Arterial occlusion
    Atrial fibrillation
    Atrial flutter
    Blurred vision
    Cardiac disorders
    Cardiac failure
    Cerebral artery stenosis
    Cerebral infarct
    Cerebrovascular occlusion
    Coronary artery disorder
    Decreased appetite
    Decreased ejection fraction
    Deep vein thrombosis (DVT)
    Dry eyes
    Dry mouth
    Electrolyte disturbances
    Elevated amylase levels
    Elevated serum lipase
    Erectile dysfunction
    Exfoliative dermatitis
    Eyelid oedema
    Facial oedema
    Febrile neutropenia
    Fluid retention
    Gastro-intestinal disturbances
    Gastro-intestinal haemorrhage
    Gastroesophageal reflux disease
    Increases in hepatic enzymes
    Influenza-like symptoms
    Left ventricular failure
    Muscle spasm
    Musculoskeletal pain
    Myocardial infarction
    Pericardial effusion
    Periorbital oedema
    Peripheral neuropathy
    Peripheral oedema
    Peripheral vascular disorders
    Pleural effusion
    Posterior reversible encephalopathy syndrome (PRES)
    Pulmonary embolism
    Reactivation of hepatitis B
    Reduced neutrophil count
    Reduced platelet count
    Retinal vein occlusion
    Retinal vein thrombosis
    Serum bilirubin increased
    Skin disorder
    Stevens-Johnson syndrome
    Tumour lysis syndrome
    Vascular disorders
    Weight loss
    White blood cell count decreased


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: March 2020

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Iclusig 15mg, 30mg and 45mg tablets. Incyte Biosciences UK Ltd. Revised August 2019.

    MHRA Drug Safety Update October 2018
    Available at:
    Last accessed: 11 January 2019

    MHRA Drug Safety Update July 2020
    Available at:
    Last accessed: 10 November 2020

    NICE Evidence Services Available at: Last accessed: 11 January 2019

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