Iclusig® (ponatinib) REMS

Iclusig REMS (Risk Evaluation and Mitigation Strategy)

A REMS is a program required by the Food and Drug Administration (FDA) to manage known or potential serious risks associated with a
drug product.


The purpose of the Iclusig REMS is to inform Healthcare Providers about the new safety information in the revised label including the serious risks of Iclusig. Safety updates include:

  • Revised indications
  • New safety information about serious risk of vascular occlusion
  • New dosing considerations

Revised Indications

The indications have been limited to:

  • Treatment of adult patients with T315I-positive chronic myeloid leukemia (CML) (chronic phase, accelerated phase, or blast phase) or
    T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)
  • Treatment of adult patients with chronic phase, accelerated phase, or blast phase CML or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated

Updated Serious Risk of Vascular Occlusion in boxed warning

Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig clinical trial patients, including:

  • Fatal myocardial infarction
  • Severe peripheral vascular disease
  • Stroke
  • Need for urgent revascularization procedures
  • Stenosis of the large arterial vessels of the brain

Iclusig can cause fatal and life-threatening vascular occlusion within 2 weeks of starting treatment. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events.

Table 1: Vascular Occlusion Incidence in Iclusig-Treated Patients in Phase 2 Trial According to Risk Categories
Prior history of ischemia, hypertension, diabetes, or hyperlipidemia No history of ischemia, hypertension, diabetes, or hyperlipidemia
Total 24% (109/449)
Age: 49 or younger 18% (6/33) 12% (13/112)
Age: 50 to 74 years 33% (50/152) 18% (20/114)
Age: 75 and older 56% (14/25) 46% (6/13)
All age groups 33% (70/210) 16% (39/239)

New Dosing Considerations

Optimal dosing has not been identified.

In clinical trials, the starting dose of Iclusig was 45 mg administered orally once daily. However, 59% of the patients required dose reductions to
30 mg or 15 mg once daily during the course of therapy.

Start dosing with 45 mg once daily. Consider reducing the dose of Iclusig for chronic phase CML (CP-CML) and accelerated phase CML (AP-CML) patients who have achieved a major cytogenetic response.

Consider discontinuing Iclusig if response has not occurred by 3 months (90 days).

Do not restart Iclusig in patients with arterial or venous occlusive reactions unless the potential benefit outweighs the risk of recurrent arterial or venous occlusions and the patient has no other treatment options.

WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY

Vascular Occlusion:

  • Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig-treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events.
  • Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit-risk consideration should guide a decision to restart Iclusig therapy.

Heart Failure:

  • Heart failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.

Hepatotoxicity:

  • Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.

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