Dosage and Administration (2.7)             07/2014
Warnings and Precautions (5.2) (5.3)      07/2014

Jakafi is a kinase inhibitor indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. (1)

• The starting dose of Jakafi is 20 mg given orally twice daily for patients with a platelet count greater than 200 X 109/L, and 15 mg twice daily for patients with a platelet count between 100 X 109/L and 200 X 109/L. (2.1)
• The starting dose of Jakafi is 5 mg twice daily for patients with a platelet count between 50 X 109/L and less than 100 X 109/L. (2.1)
• Monitor complete blood counts every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. Modify or interrupt dosing for thrombocytopenia. (2.1) (2.2)
• Increase dose based on response and as recommended to a maximum of 25 mg twice daily for patients with starting platelet counts 100 X 109/L or greater and to a maximum of 10 mg twice daily for patients with starting platelet count between 50 X 109/L and less than 100 X 109/L. Discontinue after 6 months if no spleen reduction or symptom improvement (2.3) (2.5)

Tablets: 5 mg, 10 mg, 15 mg, 20 mg and 25 mg. (3)

None. (4)

• Thrombocytopenia, Anemia and Neutropenia: Manage by dose reduction, or interruption, or transfusion. (5.1)
• Risk of Infection: Assess patients for signs and symptoms of infection and initiate appropriate treatment promptly. Serious infections should have resolved before starting therapy with Jakafi. (5.2)
• Myelofibrosis Symptom Exacerbation Following Interruption or Discontinuation: Manage with supportive care and consider resuming treatment with Jakafi. (5.3)

The most common hematologic adverse reactions (incidence > 20%) are thrombocytopenia and anemia. The most common non-hematologic adverse reactions (incidence >10%) are bruising, dizziness and headache. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong CYP3A4 Inhibitors or Fluconazole: Reduce, interrupt, or discontinue Jakafi doses as recommended. (2.7) (7.1). Avoid use of Jakafi with fluconazole doses greater than 200 mg.

• Renal Impairment: Reduce Jakafi starting dose to 10 mg twice daily for patients with moderate (CrCl 30-59 mL/min) or severe renal impairment (CrCl 15-29 mL/min) and a platelet count between 100 X 109/L and 150 X 109/L. Avoid in patients with end stage renal disease (CrCl less than 15 mL/min) not requiring dialysis. Avoid in patients with moderate or severe renal impairment and a platelet count less than 100 X 109/L. (2.8) (8.6)
• Hepatic Impairment: Reduce Jakafi starting dose to 10 mg twice daily for patients with any degree of hepatic impairment and a platelet count between 100 X 109/L and 150 X 109/L. Avoid in patients with hepatic impairment with platelet counts less than 100 X 109/L. (2.8) (8.7)
• Nursing Mothers: Discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother. (8.3)