Iclusig Dosage/Direction for Use

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: CML, Ph+ ALL who are resistant/intolerant to dasatinib or other TKIs; or who have the T315I mutation. 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 major cytogenetic 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 Precautions and Pharmacology: Pharmacodynamics under Actions). If dose reduction is undertaken, close monitoring of response is recommended.
Newly Diagnosed Ph+ ALL: The recommended starting dosage of ICLUSIG in combination with chemotherapy is 30 mg orally once daily with a reduction to 15 mg orally once daily upon achievement of MRD-negative (≤0.01% BCR::ABL1/ABL1) CR at the end of induction. Patients with loss of MRD negativity can re-escalate the dose of ICLUSIG to a previously tolerated dosage of up to 30 mg orally once daily. After completion of ICLUSIG in combination with chemotherapy, continue treatment with Iclusig as single agent therapy until loss of response at the re-escalated dose or unacceptable toxicity. For a description of dosing of agents administered in combination with ICLUSIG.
Management of toxicities: 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.
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 film-coated tablets are available.
Myelosuppression: Dose modifications for neutropenia (ANC* <1.0 x 10⁹/L) and thrombocytopenia (platelet <50 x 10⁹/L) that are unrelated to leukaemia are summarized in Table 7. (See Table 7.)

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Arterial occlusion and venous thromboembolism: 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 Precautions and Adverse Reactions) 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 8. (See Table 8.)

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Hepatic toxicity: Dose interruption or discontinuation may be required as described in Table 9. (See Table 9.)

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Elderly patients: CML, Ph+ ALL who are resistant/intolerant to dasatinib or other TKIs; or who have the T315I mutation. Of the 449 patients in the clinical study of Iclusig, 155 (35%) were ≥65 years of age. Compared to patients <65 years, older patients are more likely to experience adverse reactions.
Newly Diagnosed Ph+ ALL: Of the 163 patients with Ph+ ALL who received Iclusig in PhALLCON, 21% were 65 years and older and 7% were 75 years and older. Overall, no differences in efficacy of Iclusig were observed between patients 65 years of age or older compared to younger patients. AOEs occurred in 21% (7/34) of patients 65 years and older and 2.3% (3/129) of patients less than 65 years of age.
Hepatic impairment: For patients with CP-CML, AP-CML, BP-CML, and Ph+ ALL receiving monotherapy, reduce the starting dose of ICLUSIG from 45 mg orally once daily to 30 mg orally once daily in patients with pre-existing hepatic impairment (Child-Pugh A, B, or C). For patients with newly diagnosed Ph+ ALL, no dosage adjustment is recommended when administering ICLUSIG to patients with mild hepatic impairment (Child-Pugh A). Closely monitor patients with moderate or severe hepatic impairment (Child-Pugh B or C) and modify the ICLUSIG dosage in the event of adverse reactions.
Renal impairment: 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.
Paediatric population: The safety and efficacy of Iclusig in patients less than 18 years of age have not been established. No data are available.
Method of administration: Iclusig is for oral use. The tablets should be swallowed whole. Patients should not crush or dissolve the tablets. Iclusig may be taken with or without food.
Patients should be advised not to swallow the desiccant canister found in the bottle.