Ruxolitinib

JAKAFI/JAKAFI XR is a kinase inhibitor indicated for treatment of: intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis in adults. polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea. steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older. chronic graft-versus-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Ruxolitinib, a kinase inhibitor, inhibits Janus Associated Kinases (JAKs), JAK1 and JAK2, which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus leading to modulation of gene expression. MF and PV are myeloproliferative neoplasms (MPNs) known to be associated with dysregulated JAK1 and JAK2 signaling. In a mouse model of JAK2V617F-positive MPN, oral administration of ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (eg, TNF-α, IL-6).

Doses should be individualized based on safety and efficacy. Starting doses per indication are noted below. Myelofibrosis. The starting dose of JAKAFI/JAKAFI XR is based on patient’s baseline platelet count: • Greater than 200 × 10 9 /L: JAKAFI 20 mg given orally twice daily or JAKAFI XR 44 mg given orally once daily. • 100 x 10 9 /L to 200 x 10 9 /L: JAKAFI 15 mg given orally twice daily or JAKAFI XR 33 mg given orally once daily. • 50 x 10 9 /L to less than 100 x 10 9 /L: JAKAFI 5 mg given orally twice daily or JAKAFI XR 11 mg given orally once daily. Polycythemia Vera. The starting dose of JAKAFI is 10 mg given orally twice daily or JAKAFI XR 22 mg given orally once daily. Acute Graft-Versus-Host Disease. The starting dose of JAKAFI is 5 mg given orally twice daily or JAKAFI XR 11 mg given orally once daily. Chronic Graft-Versus-Host Disease.

None. None.

Thrombocytopenia, Anemia, and Neutropenia: Manage by dose reduction or interruption, or transfusion. 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/JAKAFI XR. Symptom Exacerbation Following Interruption or Discontinuation: Manage with supportive care and consider resuming treatment with JAKAFI/JAKAFI XR. Risk of Non-Melanoma Skin Cancer: Perform periodic skin examinations. Lipid Elevations: Assess lipid levels 8 to 12 weeks from start of therapy and treat as needed. Major Adverse Cardiovascular Events (MACE): Monitor for development of MACE. Thrombosis: Evaluate and treat symptoms of thrombosis promptly. Secondary Malignancies: Monitor for development of secondary malignancies, particularly in patients who are current or past smokers.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Thrombocytopenia, Anemia and Neutropenia Risk of Infection Symptom Exacerbation Following Interruption or Discontinuation of Treatment Non-Melanoma Skin Cancer Lipid Elevations Major Adverse Cardiovascular Events (MACE) Thrombosis Secondary Malignancies In myelofibrosis and polycythemia vera, the most common hematologic adverse reactions (incidence > 20%) are thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥ 15%) are bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common hematologic adverse reactions (incidence > 50%) are anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions (incidence > 50%) are infections (pathogen not specified) and edema.

Fluconazole: Avoid concomitant use with fluconazole doses greater than 200 mg. Reduce JAKAFI/JAKAFI XR dosage with fluconazole doses less than or equal to 200 mg. Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue JAKAFI/JAKAFI XR doses as recommended except in patients with acute or chronic graft-versus-host-disease.

Store JAKAFI/JAKAFI XR at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light.