Page 1022 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 57 Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies 905

Therapeutic Indications in Hematology: Philadelphia removed by dialysis, although some active metabolites may be
chromosome–positive chronic myelogenous leukemia and Philadel- removed; therefore, the drug should be administered after dialysis.
phia chromosome–positive acute lymphoblastic leukemia.
Preparation and Administration: Ruxolitinib is supplied as a
5- and 10-mg round tablet, a 15- and 25-mg oval tablet, as well as a
JANUS KINASE INHIBITORS 20-mg capsule. For patients unable to ingest tablets, Jakafi can be
administered PO by suspending one tablet in approximately 40 mL
Ruxolitinib of water with stirring for approximately 10 minutes.

Chemistry and Mechanism of Action: Ruxolitinib is a JAK Toxic Effects: Ruxolitinib has been shown to cause myelosuppres-
inhibitor (JAK1 and JAK2) that inhibits dysregulated JAK signaling sion, progressive multifocal leukoencephalopathy, and infections such
associated with myelofibrosis. JAK signaling involves recruitment of as Herpes zoster.
signal transducers and activators of transcription (STATs) to cytokine
receptors, activation, and subsequent localization of STATs to the Potential Drug Interactions: All drugs undergoing metabolism
nucleus, leading to modulation of gene expression. by the CYP3A4 pathway should be used with caution,

Absorption, Fate, and Excretion: Ruxolitinib is 95% absorbed Therapeutic Indications in Hematology: Myelofibrosis and
and 97 % protein bound. Ruxolitinib is metabolized primarily by polycythemia vera,
CYP3A4, with a half-life of approximately 3 hours. Ruxolitinib is not