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Iclusig is a brand name for Ponatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Iclusig is indicated in adult patients with • chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I…
Verbatim from this product's EMA label. Tap a section to expand.
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.
Posology Patients with CML and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) previously treated with other tyrosine kinase inhibitors (TKIs) or who have the T315I mutation: The recommended starting dose is 45 mg of ponatinib once daily.
For the standard dose of 45 mg once daily, a 45 mg film-coated tablet is available. 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. e. 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 dosage 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.
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 dosage of up to 30 mg once daily. 1 Pharmacodynamic properties). 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.
4 Discontinuing ponatinib should be considered if a complete molecular response has not occurred after the induction phase. Management of toxicities Iclusig dose modifications or interruption of dosing should be considered for the management of haematological and non-haematological toxicities.
0%). Serious arterial cardiovascular, cerebrovascular, and peripheral vascular occlusive adverse reactions (treatment-emergent frequencies) occurred in 10%, 7%, and 9% of Iclusig-treated patients, respectively. Serious venous occlusive reactions (treatment-emergent frequencies) occurred in 5% of patients.
Arterial cardiovascular, cerebrovascular, and peripheral vascular occlusive adverse reactions (treatment-emergent frequencies) occurred in 13%, 9%, and 11% of Iclusig-treated patients, respectively. Overall arterial occlusive adverse reactions have occurred in 25% of Iclusig-treated patients from the PACE phase 2 trial with a minimum 64 months follow-up, with serious adverse reactions occurring in 20% of patients.
Some patients experienced more than one type of event. 11 Venous thromboembolic reactions (treatment-emergent frequencies) occurred in 6% of patients. The incidence of thromboembolic events is higher in patients with Ph+ ALL or BP-CML than those with AP-CML or CP-CML.
No venous occlusive events were fatal. After a minimum follow-up of 64 months, the rates of adverse reactions resulting in discontinuation were 20% in CP-CML, 11% in AP-CML, 15% in BP-CML and 9% in Ph+ ALL. 5% of patients (45 mg cohort).
3% of Iclusig-treated patients (45 mg cohort), respectively. Of the 94 patients in the 45 mg cohort, 1 patient experienced a venous thromboembolic reaction (Grade 1 retinal vein occlusion). Patients with Newly Diagnosed Ph+ ALL (PhALLCON Study) In Ph+ ALL patients treated with ponatinib in combination with reduced-intensity chemotherapy, the safety profile was consistent with the safety profile of ponatinib alone in terms of type of events.
Myelosuppression events were reported in 83 % of ponatinib-treated patients in PhALLCON. The most frequently reported adverse drug reactions were thrombocytopenia (47%), neutropenia (44%) and anemia (44%). Events of hepatotoxicity occurred in 64 % of patients.
Important adverse reactions Myelosuppression Iclusig is associated with severe (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) thrombocytopenia, neutropenia, and anaemia. Most of the patients with grade 3 or 4 platelet count decreased, anaemia or neutropenia, developed it within the first 3 months of treatment.
The frequency of these events is greater in patients with accelerated phase CML (AP-CML), blast phase CML (BP-CML), or Ph+ ALL than in chronic phase CML (CP-CML). A complete blood count should be performed every 2 weeks for the first 3 months and then monthly or as clinically indicated.
2). Arterial occlusion Arterial occlusions, including fatal myocardial infarction, stroke, retinal arterial occlusions associated in some cases with permanent visual impairment or vision loss, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, renal artery stenosis (associated with worsening, labile or treatment-resistant hypertension), and the need for urgent revascularization procedures have occurred in Iclusig-treated patients.
Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Arterial occlusion adverse events were more frequent with increasing age and in patients with history of ischaemia, hypertension, diabetes, or hyperlipidaemia.
1). 8). Some patients experienced more than 1 type of event. 8). 7 In these patients, alternative treatment options should also be considered before starting treatment with ponatinib. 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 safety of ponatinib treatment has not been studied in patients with atrial fibrillation.
1.
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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.
For a dose of 30 mg or 15 mg once daily, 15 mg and 30 mg film-coated tablets are available. 0 x 109/L) and thrombocytopenia (platelet < 50 x 109/L) that are unrelated to leukaemia are summarized in Table 1. 5 x 109/L and platelet ≥ 75 x 109/L *ANC = absolute neutrophil count Arterial occlusion and venous thromboembolism In a patient suspected of developing an arterial occlusive event or a venous thromboembolism, Iclusig should be immediately interrupted.
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. Pancreatitis Recommended modifications for pancreatic adverse reactions are summarized in Table 2.
0 x IULN) Occurrence at 45 mg: • Iclusig should be withheld until complete resolution of symptoms and after recovery of lipase elevation to < Grade 2 and resumed at […]
Overall a higher incidence of myelosuppression associated with chemotherapy (febrile neutropenia, pyrexia, pneumonia and sepsis) as well as peripheral sensory neuropathy and stomatitis was observed as compared to the use of ponatinib alone.
Tabulated lists of adverse reactions The frequencies of adverse reactions of Iclusig monotherapy are based on 449 CML and Ph+ ALL patients exposed to ponatinib in the PACE phase 2 trial and the 94 CML patients exposed to ponatinib (45 mg starting dose) in the OPTIC phase 2 trial.
1 for information on the main characteristics of participants in the trials. Adverse reactions reported in all CML and Ph+ ALL patients are listed by system organ class and by frequency in Table 4. The frequencies of adverse reactions of Iclusig in combination with chemotherapy are based on 163 newly diagnosed Ph+ ALL patients exposed to ponatinib in combination with reduced-intensity chemotherapy followed by continued treatment with Iclusig as monotherapy in the PhALLCON phase 3 trial.
1 for information on the main characteristics of participants in the trial. Adverse reactions reported in all newly diagnosed Ph+ ALL patients are listed by system organ class and by frequency in Table
Monitoring for evidence of arterial occlusion should be performed and if decreased vision or blurred vision occurs, an ophthalmic examination (including fundoscopy) should be performed. Iclusig should be interrupted immediately in case of arterial occlusion.
8). Venous thromboembolism Venous thromboembolic adverse reactions including serious reactions have occurred in the clinical development. 8). Monitoring for evidence of thromboembolism should be performed. Iclusig should be interrupted immediately in case of thromboembolism.
8). Retinal venous occlusions associated in some cases with permanent visual impairment or vision loss have occurred in Iclusig-treated patients. If decreased vision or blurred vision occurs, an ophthalmic examination (including fundoscopy) should be performed.
Hypertension Hypertension may contribute to risk of arterial thrombotic events, including renal artery stenosis. During Iclusig treatment, blood pressure should be monitored and managed at each clinic visit and hypertension should be treated to normal.
2). In the event of significant worsening, labile or treatment-resistant hypertension, treatment should be interrupted and evaluation for renal artery stenosis should be considered. Treatment-emergent hypertension (including hypertensive crisis) occurred in Iclusig-treated patients.
Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. Aneurysms and artery dissections The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections.
Before initiating Iclusig, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm. Congestive heart failure Fatal and serious heart failure or left ventricular dysfunction occurred in Iclusig-treated patients, including events related to prior vascular occlusive events.
Patients should be monitored for signs or symptoms consistent with heart failure and they should be treated as clinically indicated, including interruption of Iclusig. 8). Pancreatitis and serum lipase Iclusig is associated with pancreatitis.
The frequency of pancreatitis is greater in the first 2 months of use. Check serum lipase every 2 weeks for the first 2 months and then periodically thereafter. Dose interruption or reduction may be required. 2). Caution is recommended in patients with a history of pancreatitis or alcohol abuse.
Patients with 8 severe or very severe hypertriglyceridemia should be appropriately managed to reduce the risk of pancreatitis. Hepatotoxicity Iclusig may result in elevation in ALT, AST, bilirubin, and alkaline phosphatase. Most patients […]