Jakafi

5 mg tablets - round and white with "INCY" on one side and "5" on the other.

10 mg tablets - round and white with "INCY" on one side and "10" on the other.

15 mg tablets - oval and white with "INCY" on one side and "15" on the other.

20 mg tablets - capsule-shaped and white with "INCY" on one side and "20" on the other.

25 mg tablets - oval and white with "INCY" on one side and "25" on the other.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

• Thrombocytopenia, Anemia and Neutropenia
  [see Warnings and Precautions (

  5.1 Thrombocytopenia, Anemia and Neutropenia

  Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia

  [

  see Adverse Reactions (

  6.1

  )]

  .

  Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary

  [

  see Dosage and Administration (

  2

  )

  ]

  .

  Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi.

  Severe neutropenia (ANC less than 0.5 × 10⁹/L) was generally reversible by withholding Jakafi until recovery.

  Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated

  [

  see Dosage and Administration (

  2

  )]

  .

  )]
• Risk of Infection
  [see Warnings and Precautions (

  5.2 Risk of Infection

  Serious bacterial, mycobacterial, fungal and viral infections have occurred

  [

  see Adverse Reactions (

  6.1

  )]

  . Delay starting therapy with Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

  Tuberculosis

  Tuberculosis infection has been reported in patients receiving Jakafi. Observe patients receiving Jakafi for signs and symptoms of active tuberculosis and manage promptly.

  Prior to initiating Jakafi, patients should be evaluated for tuberculosis risk factors, and those at higher risk should be tested for latent infection. Risk factors include, but are not limited to, prior residence in or travel to countries with a high prevalence of tuberculosis, close contact with a person with active tuberculosis, and a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed.

  For patients with evidence of active or latent tuberculosis, consult a physician with expertise in the treatment of tuberculosis before starting Jakafi. The decision to continue Jakafi during treatment of active tuberculosis should be based on the overall risk-benefit determination.

  Progressive Multifocal Leukoencephalopathy

  Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate.

  Herpes Zoster and Herpes Simplex

  Herpes zoster infection has been reported in patients receiving Jakafi

  [see Adverse Reactions ]

  . Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible if suspected.

  Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi

  [see Adverse Reactions ]

  . Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines.

  Hepatitis B

  
  
  

  Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking Jakafi. The effect of Jakafi on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines.

  )]
• Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi
  [see Warnings and Precautions (

  5.3 Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi

  Following discontinuation of Jakafi, symptoms from myeloproliferative neoplasms may return to pretreatment levels over a period of approximately one week. Some patients with MF have experienced one or more of the following adverse events after discontinuing Jakafi: fever, respiratory distress, hypotension, DIC, or multi-organ failure. If one or more of these occur after discontinuation of, or while tapering the dose of Jakafi, evaluate for and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician. When discontinuing or interrupting therapy with Jakafi for reasons other than thrombocytopenia or neutropenia

  [see Dosage and Administration ]

  , consider tapering the dose of Jakafi gradually rather than discontinuing abruptly.

  )]
• Non-Melanoma Skin Cancer
  [see Warnings and Precautions (

  5.4 Non-Melanoma Skin Cancer (NMSC)

  Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred in patients treated with Jakafi. Perform periodic skin examinations.

  )]
  
  
  
• Lipid Elevations
  [
  see Warnings and Precautions (
  5.5
  )]
• Major Adverse Cardiovascular Events (MACE)
  [
  see Warnings and Precautions (
  5.6
  )]
• Thrombosis
  [
  see Warnings and Precautions (
  5.7
  )]
• Secondary Malignancies 
  [
  see Warnings and Precautions (
  5.8
  )]

Ruxolitinib phosphate is a kinase inhibitor with the chemical name (

Ruxolitinib phosphate is a white to off-white to light pink powder and is soluble in aqueous buffers across a pH range of 1 to 8.

Jakafi (ruxolitinib) Tablets are for oral administration. Each tablet contains 6.6 mg, 13.2 mg, 19.8 mg, 26.4 mg, or 33 mg of ruxolitinib phosphate equivalent to 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxolitinib free base, respectively, together with microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone and hydroxypropyl cellulose.

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 (MPN) 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 (e.g., TNF-α, IL-6).

JAK-STAT signaling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GVHD pathogenesis. In a mouse model of aGVHD, oral administration of ruxolitinib was associated with decreased expression of inflammatory cytokines in colon homogenates and reduced immune-cell infiltration in the colon.