Ruxolitinib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- Ruxolitinib
Contraindications
None.
Adverse Reactions
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)] Risk of Infection [see Warnings and Precautions (5.2)] Symptom Exacerbation Following Interruption or Discontinuation of Treatment [see Warnings and Precautions (5.3)] Non-Melanoma Skin Cancer [see Warnings and Precautions (5.4)] 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 )]
Mechanism of Action
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). 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.
Overdosage
There is no known antidote for overdoses with JAKAFI/JAKAFI XR. Single doses up to 200 mg have been given with acceptable acute tolerability. Higher than recommended repeat doses are associated with increased myelosuppression including leukopenia, anemia, and thrombocytopenia. Appropriate supportive treatment should be given. Hemodialysis is not expected to enhance the elimination of JAKAFI/JAKAFI XR.