|Pronunciation||Jakafi // JAK-ə-fye|
|Trade names||Jakafi, Jakavi|
|Other names||INCB018424, INC424|
|Drug class||Kinase inhibitor|
|Main uses||Myelofibrosis, polycythemia vera (PCV), graft-versus-host disease|
|Side effects||Low platelets, low red blood cells, low neutrophils, bleeding, liver problems, abnormal lipids|
|Interactions||CYP3A4 inhibitors, fluconazole|
|Typical dose||5 to 20 mg BID|
|Metabolism||Liver (mainly CYP3A4-mediated)|
|Elimination half-life||2.8-3 hours|
|Excretion||Urine (74%), faeces (22%)|
|Chemical and physical data|
|Molar mass||306.373 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Ruxolitinib, sold under the brand names Jakafi and Jakavi, is a medication used to treat myelofibrosis, polycythemia vera (PCV), and graft-versus-host disease (GvHD). It is used in PCV when hydroxyurea is not sufficient and in GvHD that is unresponsive to other measures. It is taken by mouth.
Common side effects include low platelets, low red blood cells, low neutrophils, bleeding, liver problems, and abnormal lipids. Other side effects may include infection, skin cancer, blood clots, and heart disease. Use in pregnancy may harm the baby. It is a kinase inhibitor.
Ruxolitinib was approved for medical use in the United States in 2011 and Europe in 2012. In the United States it costs about 15,800 USD per month as of 2021. In the United Kingdom this amount costs the NHS about £3,000.
In the United States and the European Union, ruxolitinib is indicated for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis or post-essential thrombocythaemia myelofibrosis. It is also indicated for the treatment of adults with polycythaemia vera who are resistant to or intolerant of hydroxyurea.
In the United States, ruxolitinib is also indicated for the treatment of steroid-refractory acute graft-versus-host disease in people who are twelve years of age and older.
It is used at a dose of 5 mg to 20 mg twice per day.
In myelofibrosis, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), neutropenia (low levels of neutrophils), urinary tract infections (infection of the structures that carry urine), bleeding, bruising, weight gain, hypercholesterolaemia (high blood cholesterol levels), dizziness, headache and raised liver enzyme levels.
In polycythaemia vera, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), bleeding, bruising, hypercholesterolaemia (high blood cholesterol levels), hypertriglyceridemia (high blood fat levels), dizziness, raised liver enzyme levels and high blood pressure.
In acute graft-versus-host disease, the most common hematologic adverse reactions include anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions include infections and edema.
Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels.
Mechanism of action
Ruxolitinib is a janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.
The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size and relieving debilitating symptoms.
Society and culture
In November 2011, ruxolitinib was approved by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate or high-risk myelofibrosis based on results of the COMFORT-I and COMFORT-II Trials.
In February 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy.
As of September 2019, a clinical trial was in progress to evaluate "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".[full citation needed][needs update]
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- Clinical trial number NCT01431209 for "Ruxolitinib Phosphate (Oral JAK Inhibitor INCB18424) in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma" at ClinicalTrials.gov
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- Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, et al. (December 2015). "Targeting senescent cells enhances adipogenesis and metabolic function in old age". eLife. 4: e12997. doi:10.7554/eLife.12997. PMC 4758946. PMID 26687007.
- Clinical trial number NCT03610971 for "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors" at ClinicalTrials.gov