Table 1.

Ponatinib background information.

Structure
Mechanism of Action	Ponatinib is a kinase inhibitor that inhibits the activity of ABL and T315I mutant ABL
Pharmacokinetics	The mean Cmax and AUC(0-24) of ponatinib 45 mg orally once daily at presumed steady state in patients with advanced hematologic malignancies were 73 ng/mL (74%) and 1253 ng·h/mL (73%), respectively. Peak concentrations of ponatinib are observed within 6 hours of oral administration. Food had no clinically significant effect on ponatinib exposure. Ponatinib is 99% plasma bound in vitro with no displacement in vitro by other highly plasma bound medications. The mean terminal elimination half-life was approximately 24 (12-66) hours. At least 64% of a dose undergoes phase I and II metabolism. CYP3A4 and, to a lesser extent, CYP2C8, CYP2D6, and CYP3A5 are involved in the phase I metabolism. Following a single oral dose of radiolabeled ponatinib, 87% of the dose was recovered in the feces and 5% in the urine.
Prior Approvals	December 2012: For adults with CML in chronic, accelerated, or blast phase that is resistant or intolerant to prior TKI therapy or Ph+ ALL that is resistant or intolerant to prior TKI therapy; withdrawn. December 2013: For adults with CML in chronic, accelerated, or blast phase or Ph+ ALL withT315I mutation or for whom no other TKI therapy is indicated June 2016: Indications updated to explicitly state that ponatinib is not indicated and not recommended for treatment of patients with newly diagnosed chronic phase CML.

Abbreviation: TKI, tyrosine kinase inhibitors.