Elevation of AST or ALT ≥ 3 × ULN concurrent with an elevation of bilirubin > 2 × ULN and alkaline phosphatase < 2 × ULN Discontinue Iclusig
Pancreatitis and Elevation of Lipase

Recommended modifications for pancreatic adverse reactions are summarized in Table 3.
Table 3: Recommended Dose Modifications for Pancreatitis and Elevation of Lipase
Asymptomatic Grade 1 or 2 elevation of serum lipase Consider interruption or dose reduction of Iclusig
Asymptomatic Grade 3 or 4 elevation of lipase (> 2 × ULN*) or asymptomatic radiologic pancreatitis (Grade 2 pancreatitis) Occurrence at 45 mg:
•Interrupt Iclusig and resume at 30 mg after recovery to ≤ Grade 1 (< 1.5 × ULN)
  
Occurrence at 30 mg:  
•Interrupt Iclusig and resume at 15 mg after recovery to ≤ Grade 1
  
Occurrence at 15 mg:  
•Discontinue Iclusig
  
Symptomatic Grade 3 pancreatitis Occurrence at 45 mg:
•Interrupt Iclusig and resume at 30 mg complete resolution of symptoms and after recovery of lipase elevation to ≤ Grade 1
  
Occurrence at 30 mg:  
•Interrupt Iclusig and resume at 15 mg after complete resolution of symptoms and after recovery of lipase elevation to ≤ Grade 1
  
Occurrence at 15 mg:  
•Discontinue Iclusig
  
Grade 4 pancreatitis Discontinue Iclusig
Dose Modification for Use With Strong CYP3A Inhibitors
The recommended dose should be reduced to 30 mg once daily when administering Iclusig with strong CYP3A inhibitors [see Drug Interactions (7.1)].

Dosage Forms and Strengths
15 mg and 45 mg round, white, film-coated tablets
Contraindications
None

Warnings and Precautions
Thrombosis and Thromboembolism
Arterial Thrombosis

Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction and stroke have occurred in Iclusig-treated patients.

Serious arterial thrombosis occurred in 8% (34/449) of Iclusig-treated patients. Twenty-one patients required a revascularization procedure (16 patients with coronary revascularization, 4 patients with peripheral arterial revascularization, and 1 patient with cerebrovascular revascularization). Overall, fifty-one patients (11%) experienced an arterial thrombosis event of any grade.

Myocardial infarction or worsening coronary artery disease was the most common arterial thrombosis event and occurred in 21 patients (5%) of Iclusig-treated patients. Eleven of these patients developed congestive heart failure concurrent or subsequent to the myocardial ischemic event.

Serious cerebrovascular events were reported in 2% (8/449) of Iclusig-treated patients. Two patients experienced hemorrhagic conversion of the initial ischemic event. Four patients developed stenosis of large art