Source: European Medicines Agency (EU) Revision Year: 2026 Publisher: Incyte Biosciences Distribution B.V., Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands
Iclusig is indicated as monotherapy in adult patients with
Iclusig is indicated in combination with reduced-intensity chemotherapy in adult patients with newly diagnosed Ph+ ALL (see section 5.1).
Iclusig is indicated as monotherapy in paediatric patients 6 years of age or older with
See sections 4.2 for the assessment of cardiovascular status prior to start of therapy and 4.4 for situations where an alternative treatment may be considered.
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with leukaemia. Haematologic support such as platelet transfusion and haematopoietic growth factors can be used during treatment if clinically indicated.
Before starting treatment with ponatinib, the cardiovascular status of the patient should be assessed, including history and physical examination, and cardiovascular risk factors should be actively managed. Cardiovascular status should continue to be monitored and medical and supportive therapy for conditions that contribute to cardiovascular risk should be optimised during treatment with ponatinib.
The recommended starting dose is 45 mg of ponatinib once daily. Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Patients should be monitored for response according to standard clinical guidelines.
Discontinuing ponatinib should be considered if a complete haematologic response has not occurred by 3 months (90 days).
The risk of arterial occlusive events is likely to be dose-related. Reducing the dose of Iclusig to 15 mg should be considered for CP-CML patients who have achieved a molecular response (MR2 i.e. ≤1% BCR-ABL1IS) taking the following factors into account in the individual patient assessment: cardiovascular risk, side effects of ponatinib therapy, time to response, and BCR-ABL transcript levels (see sections 4.4 and 5.1). If dose reduction is undertaken, close monitoring of response is recommended. In patients with loss of response the dose of Iclusig can be re-escalated to a previously tolerated dose of 30 mg or 45 mg orally once daily. Iclusig should be continued until loss of response at the re escalated dose or unacceptable toxicity.
The recommended starting dose is 30 mg of ponatinib once daily in combination with chemotherapy with a dose reduction to 15 mg once daily upon achievement of Minimal Residual Disease (MRD)-negative complete response (≤0.01% BCR-ABL1) at the end of induction.
Patients with loss of MRD negativity can re-escalate the dose of ponatinib to a previously tolerated dose of up to 30 mg once daily. After completion of ponatinib in combination with chemotherapy, continue treatment with ponatinib as monotherapy until loss of response at the re-escalated dose or unacceptable toxicity (see section 5.1).
CNS prophylaxis or treatment, steroid induction, anti-CD20 therapy in CD20+ patients or chemotherapy as applicable should follow the respective Summaries of Product Characteristics and standard clinical guidelines.
Discontinuing ponatinib should be considered if a complete molecular response has not occurred after the induction phase.
Ponatinib is administered orally once daily in the form of either Iclusig film-coated tablets or Iclusig hard capsules. The recommended starting dose is individualized for each paediatric patient on the basis of body weight (see Table 1):
Table 1. Recommended starting dose and reduced dose after achieving a molecular response for paediatric patients with CP-CML:
| Body weight | Recommended starting dose in mg (once daily) | Recommended reduced dose in mg (once daily) |
| >45 kg | 45 mg | 15 mg |
| >30 kg to 45 kg | 30 mg | 10 mg |
| 15 to 30 kg | 15 mg | 5 mg |
Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Patients should be monitored for response according to standard clinical guidelines.
As in adults, the risk of arterial occlusive events is likely to be dose related. Reducing the dose of Iclusig according to Table 1 should be considered for paediatric CP-CML patients who have achieved a molecular response taking the following factors into account in the individual patient assessment: cardiovascular risk, side effects of ponatinib therapy, time to response, and BCR-ABL transcript levels (see sections 4.4 and 5.1). If dose reduction is undertaken, close monitoring of response is recommended. In patients with loss of response the dose of Iclusig can be re escalated to a previously tolerated daily dose. Iclusig should be continued until loss of response at the re escalated dose or unacceptable toxicity.
With the concurrent use of strong CYP3A inhibitors a reduction of the starting dose of Iclusig should be considered to 30 mg for adults and as per Table 2 below for paediatric patients (see section 4.4).
Table 2. Recommended starting dose in paediatric patients with concurrent use of strong CYP3A inhibitors:
| Body weight | Recommended starting dose in mg (once daily) |
| >45 kg | 30 mg |
| >30 kg to 45 kg | 20 mg |
| 15 to 30 kg | 10 mg |
Iclusig dose modifications or interruption of dosing should be considered for the management of haematological and non-haematological toxicities. In the case of severe adverse reactions, treatment should be withheld. When Iclusig is given in combination with chemotherapy, standard dose reductions for the chemotherapeutic medicinal products should be applied, see their respective Summary of Product Characteristics and standard clinical guidelines.
For patients whose adverse reactions are resolved or attenuated in severity, Iclusig may be restarted and escalation of the dose back to the daily dose used prior to the adverse reaction may be considered, if clinically appropriate.
Dose modifications for neutropenia and thrombocytopenia that are unrelated to leukaemia are summarized in Table 3 for adult patients and in Table 4 for paediatric patients.
Table 3. Dose modifications for myelosuppression for adult patients:
| Starting dose of ponatinib 45 mg once daily | ANC* < 1.0 x 109/L or platelet < 50 x 109/L | First occurrence: • Withhold and resume at the same dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
| Recurrence at 45 mg: • Withhold and resume at 30 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Recurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
* ANC = absolute neutrophil count
Table 4. Dose modifications for myelosuppression for paediatric patients:
| Starting dose of ponatinib 45 mg once daily | ANC* < 1.0 x 109/L or platelet < 50 x 109/L | First occurrence: • Withhold and resume at the same dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
| Recurrence at 45 mg: • Withhold and resume at 30 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Recurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Starting dose of ponatinib 30 mg once daily | ANC* < 1.0 x 109/L or platelet < 50 x 109/L | First occurrence: Withhold and resume at the same dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
| Recurrence at 30 mg: Withhold and resumed at 20 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Recurrence at 20 mg: Withhold and resume at 10 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Starting dose of ponatinib 15 mg once daily | ANC* < 1.0 x 109/L or platelet < 50 x 109/L | First occurrence: Withhold and resume at the same dose after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
| Recurrence at 15 mg: Withhold and resume at 10 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L | ||
| Recurrence at 10 mg: Withhold and resume at 5 mg after recovery to ANC ≥ 1.5 x 109/L and platelet ≥ 75 x 109/L |
* ANC = absolute neutrophil count
In a patient suspected of developing an arterial occlusive event or a venous thromboembolism, Iclusig should be immediately interrupted. A benefit-risk consideration should guide a decision to restart Iclusig therapy (see sections 4.4 and 4.8) after the event is resolved.
Hypertension may contribute to risk of arterial occlusive events. Iclusig treatment should be temporarily interrupted if hypertension is not medically controlled.
Recommended modifications for pancreatic adverse reactions are summarized in Table 5 for adult patients and in Table 6 for paediatric patients.
Table 5. Dose modifications for pancreatitis and elevation of lipase for adults:
| Starting dose of ponatinib 45 mg once daily | Grade 2 pancreatitis and/or Grade 2 elevation of lipase (> 1.5 - 2.0 x IULN or > 2.0 - 5.0 x IULN and asymptomatic) | Continue at the same dose |
| Grade 3 asymptomatic elevation of lipase (> 5.0 x IULN*) | Occurrence at 45 mg: • Withhold and resume at 30 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 15 mg: • Iclusig discontinuation should be considered | |
| Grade 3 pancreatitis or Grade 3 symptomatic elevation of lipase (> 2.0 - 5.0 x IULN) | Occurrence at 45 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 30 mg Occurrence at 30 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 15 mg Occurrence at 15 mg: • Iclusig discontinuation should be considered | |
| Grade 4 pancreatitis or Grade 4 elevation of lipase (> 5.0 x IULN and symptomatic) | Discontinue |
* IULN = institution upper limit of normal
Table 6. Dose modifications for pancreatitis and elevation of lipase for paediatric patients:
| Starting dose of ponatinib 45 mg once daily | Grade 2 pancreatitis and/or Grade 2 elevation of lipase(> 1.5 - 2.0 x IULN or > 2.0 - 5.0 x IULN and asymptomatic) | Continue at the same dose |
| Grade 3 asymptomatic elevation of lipase (> 5.0 x IULN*) | Occurrence at 45 mg: • Withhold and resume at 30 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 15 mg: • Iclusig discontinuation should be considered | |
| Grade 3 pancreatitis or Grade 3 symptomatic elevation of lipase (> 2.0 - 5.0 x IULN) | Occurrence at 45 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 30 mg Occurrence at 30 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 15 mg Occurrence at 15 mg: • Iclusig discontinuation should be considered | |
| Grade 4 pancreatitis or Grade 4 elevation of lipase (> 5.0 x IULN and symptomatic) | Discontinue | |
| Starting dose of ponatinib 30 mg once daily | Grade 2 pancreatitis and/or Grade 2 elevation of lipase (> 1.5 - 2.0 x IULN or > 2.0 - 5.0 x IULN and asymptomatic) | Continue at the same dose |
| Grade 3 asymptomatic elevation of lipase (> 5.0 x IULN*) | Occurrence at 30 mg: • Withhold and resume at 20 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 20 mg: • Withhold and resume at 10 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 10 mg: Iclusig discontinuation should be considered | |
| Grade 3 pancreatitis or Grade 3 symptomatic elevation of lipase (> 2.0 - 5.0 x IULN) | Occurrence at 30 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 20 mg Occurrence at 20 mg: Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 10 mg Occurrence at 10 mg: Iclusig discontinuation should be considered | |
| Grade 4 pancreatitis or Grade 4 elevation of lipase (> 5.0 x IULN and symptomatic) | Discontinue | |
| Starting dose of ponatinib 15 mg once daily | Grade 2 pancreatitis and/or Grade 2 elevation of lipase (> 1.5 - 2.0 x IULN or > 2.0 - 5.0 x IULN and asymptomatic) | Continue at the same dose |
| Grade 3 asymptomatic elevation of lipase (> 5.0 x IULN*) | Occurrence at 15 mg: • Withhold and resume at 10 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 10 mg: • Withhold and resume at 5 mg after recovery to ≤ Grade 1 (< 1.5 x IULN) Occurrence at 5 mg: Iclusig discontinuation should be considered | |
| Grade 3 pancreatitis or Grade 3 symptomatic elevation of lipase (> 2.0 - 5.0 x IULN) | Occurrence at 15 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 10 mg Occurrence at 10 mg: • Withhold until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resume at 5 mg Occurrence at 5 mg: Iclusig discontinuation should be considered | |
| Grade 4 pancreatitis or Grade 4 elevation of lipase (> 5.0 x IULN and symptomatic) | Iclusig should be discontinued |
* IULN = institution upper limit of normal
Dose interruption or discontinuation may be required as described in Table 7 for adult patients and in Table 8 for paediatric patients.
Table 7. Recommended dose modifications for hepatic toxicity for adults:
| Starting dose of ponatinib 45 mg once daily | Elevation of liver transaminase > 3 × ULN* Persistent Grade 2 (longer than 7 days) Grade 3 or higher | Occurrence at 45 mg: • Withhold Iclusig and monitor the hepatic function • Resume at 30 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 30 mg: • Withhold and resumeat 15 mg after recovery to ≤ Grade 1, or recovery to pre-treatment grade Occurrence at 15 mg: • Discontinue |
| Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN | Discontinue |
* ULN = Upper Limit of Normal for the lab
Table 8. Recommended dose modifications for hepatic toxicity for paediatric patients:
| Starting dose of ponatinib 45 mg once daily | Elevation of liver transaminase > 3 × ULN* Persistent Grade 2 (longer than 7 days) Grade 3 or higher | Occurrence at 45 mg: • Withhold Iclusig and monitor hepatic function • Resume at 30 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ≤ Grade 1, or recovery to pre-treatment grade Occurrence at 15 mg: • Discontinue |
| Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN | Discontinue | |
| Starting dose of ponatinib 30 mg once daily | Elevation of liver transaminase > 3 × ULN* Persistent Grade 2 (longer than 7 days) Grade 3 or higher | Occurrence at 30 mg: • Withhold Iclusig and monitor hepatic function • Resume at 20 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 20 mg: • Withhold and resume at 10 mg after recovery to ≤ Grade 1, or recovery to pre-treatment grade Occurrence at 10 mg: Discontinue |
| Starting dose of ponatinib 45 mg once daily | Elevation of liver transaminase > 3 × ULN* Persistent Grade 2 (longer than 7 days) Grade 3 or higher | Occurrence at 45 mg: • Withhold Iclusig and monitor hepatic function • Resume at 30 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 30 mg: • Withhold and resume at 15 mg after recovery to ≤ Grade 1, or recovery to pre-treatment grade Occurrence at 15 mg: • Discontinue |
| Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN | Discontinue | |
| Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN | Discontinue | |
| Starting dose of ponatinib 15 mg once daily | Elevation of liver transaminase > 3 × ULN* Persistent grade 2 (longer than 7 days) Grade 3 or higher | Occurrence at 15 mg: • Withhold Iclusig and monitor hepatic function • Resume at 10 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 10 mg: • Resume at 5 mg after recovery to ≤ Grade 1 (< 3 × ULN), or recovery to pre-treatment grade Occurrence at 5 mg: Discontinue |
| Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN | Discontinue |
* ULN = Upper Limit of Normal for the lab
Of the 732 patients in the PACE and OPTIC clinical studies of Iclusig, 191 (26%) were ≥65 years of age. Compared to patients <65 years, older patients are more likely to experience adverse reactions. No dose adjustment is required in patients aged 65 years or above.
Patients with hepatic impairment may receive the recommended starting dose. Caution is recommended when administering Iclusig to patients with hepatic impairment (see sections 4.4 and 5.2).
Renal excretion is not a major route of ponatinib elimination. Iclusig has not been studied in patients with renal impairment. Patients with estimated creatinine clearance of ≥50 mL/min should be able to safely receive Iclusig with no dosage adjustment. Caution is recommended when administering Iclusig to patients with estimated creatinine clearance of <50 mL/min, or end-stage renal disease.
The safety and efficacy of Iclusig monotherapy in children below 6 years has not been established. The safety and efficacy of Iclusig in combination with chemotherapy in children has not been established (see section 5.1).
Iclusig is for oral use. It may be taken with or without food.
Iclusig is available as film-coated tablets and hard capsules.
The tablets should be swallowed whole. The tablets should not be crushed or dissolved. For doses that cannot be achieved by using the film-coated tablets, or for paediatric patients who are unable to swallow film-coated tablets, the 5 mg hard capsules are available. The hard capsules can be swallowed whole, but for the patients who are unable to swallow them, they can be opened and the content can be dispersed in soft food (applesauce or yogurt) and taken immediately.
Isolated reports of unintentional overdose with Iclusig were reported in clinical trials. Single doses of 165 mg and an estimated 540 mg in two patients did not result in any clinically significant adverse reactions. Multiple doses of 90 mg per day for 12 days in a patient resulted in pneumonia, systemic inflammatory response, atrial fibrillation, and asymptomatic, moderate pericardial effusion. Treatment was interrupted, the events resolved, and Iclusig was restarted at 45 mg, once daily. In the event of an overdose of Iclusig, the patient should be observed and appropriate supportive treatment given.
4 years.
Store in the original container in order to protect from moisture.The bottle contains one sealed canister containing a molecular sieve desiccant. Keep the canister in the bottle.
Iclusig 15 mg film-coated tablets: High density polyethylene (HDPE) bottles with screw-top closures, containing either 30, 60 or 180 film-coated tablets, together with one plastic canister containing a molecular sieve desiccant.
Iclusig 30 mg film-coated tablets: High density polyethylene (HDPE) bottles with screw-top closures, containing 30 film-coated tablets, together with one plastic canister containing a molecular sieve desiccant.
Iclusig 45 mg film-coated tablets: High density polyethylene (HDPE) bottles with screw-top closures, containing either 30 or 90 film-coated tablets, together with one plastic canister containing a molecular sieve desiccant.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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