ICLUSIG

What it is

ICLUSIG contains ponatinib hydrochloride and is available as film-coated tablets in strengths of 10, 15, 30, or 45 mg . ICLUSIG tablets are available for oral administration .

Approved indications

ICLUSIG is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia whose disease is resistant to, or who are intolerant of at least two prior tyrosine kinase inhibitors, or where there is a T315l mutation . ICLUSIG is indicated for the treatment of adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia whose disease is resistant to, or who are intolerant of dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate, or where there is a T315l mutation .

Dosing overview

Complete blood counts should be obtained every 2 weeks for the first 3 months and then monthly or as clinically indicated, with dose adjustments made as recommended . Therapy with ICLUSIG should be initiated and monitored by a haematologist with expertise in managing adult leukaemias .

Key safety warnings

Arterial occlusive events, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease (sometimes resulting in amputation), vision loss, and the need for urgent revascularisation procedures, have occurred in ICLUSIG-treated patients . Patients with and without cardiovascular risk factors, including patients less than 50 years old, have experienced these events . Monitor for evidence of arterial occlusive events and interrupt or stop ICLUSIG based on severity . Venous thromboembolic events have occurred in ICLUSIG-treated patients . Monitor for evidence of venous thromboembolic events and interrupt or stop ICLUSIG based on severity . Heart failure, including fatalities, has occurred in ICLUSIG-treated patients; monitor cardiac function and interrupt or stop ICLUSIG for new or worsening heart failure . Hypertension, including hypertensive crisis, has been observed in ICLUSIG-treated patients . Hepatotoxicity, including liver failure and death, has occurred in ICLUSIG-treated patients; monitor hepatic function and interrupt ICLUSIG based on severity .

PBS listing

The 15 mg tablet strength is listed on the PBS with authority required restriction at an ex-manufacturer price of A$5061.77 . The 45 mg tablet strength is listed on the PBS with authority required restriction at an ex-manufacturer price of A$5711.07 .

Regulatory history

ICLUSIG ponatinib 15 mg and 45 mg tablet strengths were first registered on the ARTG on 2014-11-26 . The TGA approved ICLUSIG on 2014-11-19 following a comprehensive evaluation that addressed concerns about vascular adverse events, with the approval granted after the sponsor revised the proposed indication and implemented risk management strategies . The 10 mg and 30 mg tablet strengths were added to the ARTG on 2022-09-16 . In November 2017, the PBAC recommended a change to the listing for relapsed or refractory Ph+ ALL to include all patients regardless of T315l mutation status who have failed or are intolerant to dasatinib . In April 2018, the PBAC recommended extending the listing to include second or third line therapy for Ph+ ALL without the T315I mutation . In November 2018, the PBAC recommended amendments to the CML listing to enable telephone authority for subsequent continuing treatment and remove the six-month timeframe requirement between bone marrow biopsy and application .