Generic Name: ponatinib hydrochloride
Dosage Form: tablet, film coated
WARNING: ARTERIAL THROMBOSIS and HEPATOTOXICITY
Arterial Thrombosis:

•Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction and stroke have occurred in Iclusig-treated patients. In clinical trials, serious arterial thrombosis occurred in 8% of Iclusig-treated patients. Interrupt and consider discontinuation of Iclusig in patients who develop arterial thrombotic events [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
Hepatotoxicity:

•Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Iclusig for hepatotoxicity [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)].
Indications and Usage for Iclusig
Iclusig® (ponatinib) is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy.

This indication is based upon response rate [see Clinical Studies (14)]. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

Iclusig Dosage and Administration
Recommended Dosing
The recommended dose and schedule for Iclusig is 45 mg administered orally once daily. Continue treatment as long as the patient does not show evidence of disease progression or unacceptable toxicity.

Iclusig may be taken with or without food. Tablets should be swallowed whole.

Dose Modifications for Myelosuppression
Suggested dose modifications for neutropenia (ANC* less than 1.0 × 109/L) and thrombocytopenia (platelet less than 50 × 109/L) that are unrelated to leukemia are summarized in Table 1.

Table 1: Suggested Dose Modifications for Myelosuppression

ANC* < 1 × 109/L
or
platelet < 50 × 109/L First occurrence:
•Interrupt Iclusig and resume initial 45 mg dose after recovery to ANC ≥ 1.5 × 109/L and platelet ≥ 75 × 109/L
  
Second occurrence:  
•Interrupt Iclusig and resume at 30 mg after recovery to ANC ≥ 1.5 × 109/L and platelet ≥ 75 × 109/L
  
Third occurrence:  
•Interrupt Iclusig and resume at 15 mg after recovery to ANC ≥ 1.5 × 109/L and platelet ≥ 75 × 109/L
Dose Modifications for Non-Hematologic Adverse Reactions
If a serious non-hematologic adverse reaction occurs, modify the dose or interrupt treatment. Do not restart Iclusig in patients with serious ischemic reactions unless the potential benefit outweighs the risk of recurrent ischemia and the patient has no other treatment options. For serious reactions other than ischemia, do not restart Iclusig until the serious event has resolved or the potential benefit of resuming therapy is judged to outweigh the risk.

Hepatic Toxicity

Recommended modifications for hepatic toxicity are summarized in Table 2.
Table 2: Recommended Dose Modifications for Hepatic Toxicity *
ULN = Upper Limit of No