Drugs of interest to pathologists
Drugs related to clinical pathology
Author: Him G. Kwee, M.D. (see Reviewers/Authors page)
Revised: 24 April 2012, last major update February 2012
Copyright: (c) 2012, PathologyOutlines.com, Inc.
● A Janus kinase inhibitor
Approved by US Food and Drug Administration on November 16, 2011 for:
● Intermediate or high risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis (Jakafi, drug prescribing information, Incyte Corporation, 2011)
● Cost: $7,000 per month in 2011 (Huffington Post, November 16, 2011)
● Side effects include anemia, neutropenia and thrombocytopenia
● Patients on a strong CYP3A4 inhibitor should have a reduced dose of ruxolitinib; dosage should also be adjusted for renal or hepatic impairment
● There are no adequate or well-controlled studies of use in pregnancy
● Women taking this drug should not breastfeed (Jakafi, drug prescribing information, Incyte Corporation, 2011)
● The Janus family of kinases consists of JAK1, JAK2, JAK3 and TYK2
● Ruxolitinib inhibits JAK1 and JAK2, which mediate the signaling of cytokines and growth factors that are important for hematopoiesis and immune functions
● JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization to the nucleus, leading to modulation of gene expression
● Myelofibrosis is associated with dysregulated JAK1 and JAK2 signaling
● JAK2 V617F mutation is found in most patients with BCR-ABL negative myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia and primary myelofibrosis (Leuk Lymphoma 2008;49:388), see also myelofibrosis topic and chronic myeloid neoplasms chapter.
● Ruxolitinib can cause significant improvement in myelofibrosis patients, specifically decrease in spleen size, fatigue, pruritus, night sweats and bone pain (Blood 2009;113:2895)
End of Drugs > Drugs related to clinical pathology > Ruxolitinib phosphate
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