Rutinib

Myelofibrosis
: Jakavi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.
Polycythemia Vera
: Jakavi is indicated for treatment
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Myelofibrosis
: Jakavi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.
Polycythemia Vera
: Jakavi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.
Acute Graft-Versus-Host Disease
: Jakavi is indicated for treatment of steroid-refractory acute graft-versus host disease (GVHD) in adult and pediatric patients 12 years and older.

The most common side effects are-
Thrombocytopenia, Anemia and Neutropenia
Risk of Infection, bruising, dizziness, headache
Symptom Exacerbation Following Interruption or Discontinuation of treatment with Jakavi
Non-Melanoma Skin Cancer

Thrombocytopenia, Anemia And Neutropenia
: Treatment with Jakavi can cause thrombocytopenia, anemia and neutropenia. Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakavi. Platelet transfusions may be necessary.Patients developing anemia may require blood transfusions and/or dose modifications of Jakavi.Severe neutropenia (ANC less than 0.5 X 109/L) was generally reversible by withholding Jakavi 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.
Risk of Infection
: Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting therapy with Jakavi until active serious infections have resolved. Observe patients receiving Jakavi for signs and symptoms of infection and manage promptly.
Tuberculosis
: Tuberculosis infection has been reported in patients receiving Jakavi. Observe patients receiving Jakavi for signs and symptoms of active tuberculosis and manage promptly. Prior to initiating Jakavi, 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 Jakavi. The decision to continue Jakavi during treatment of active tuberculosis should be based on the overall risk-benefit determination.
Progressive Multifocal Leukoencephalopathy
: Progressive multifocal leukoencephalopathy (PML) has occurred with Jakavi treatment. If PML is suspected, stop Jakavi and evaluate.
Herpes Zoster
: Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible if suspected.
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 Jakavi. The effect of Jakavi 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 Jakavi
: Following discontinuation of Jakavi, 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 Jakavi: 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 Jakavi, evaluate for and treat any intercurrent illness and consider restarting or increasing the dose of Jakavi. Instruct patients not to interrupt or discontinue Jakavi therapy without consulting their physician. When discontinuing or interrupting therapy with Jakavi for reasons other than thrombocytopenia or neutropenia, consider tapering the dose of Jakavi gradually rather than discontinuing abruptly.
Non-Melanoma Skin Cancer
: Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred in patients treated with Jakavi. Perform periodic skin examinations.
Lipid Elevations
: Treatment with Jakavi has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined in patients treated with Jakavi. Assess lipid parameters approximately 8-12 weeks following initiation of Jakavi therapy. Monitor and treat according to clinical guidelines for the management of hyperlipidemia.

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. Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. Oral administration of ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (eg, TNF-α, IL-6).
Absorption
: Ruxolitinib is rapidly absorbed after oral Ruxolitinib administration with maximal plasma concentration (Cmax) achieved within 1 to 2 hours post-dose. Oral absorption of ruxolitinib was estimated to be at least 95%. Distribution: The mean volume of distribution of ruxolitinib at steady-state is 72 L in patient with MF and PV in myelofibrosis patients.
Half-life
: the mean half-life of ruxolitinib & metabolites is approximately 5.8 hours. Elimination half-life: The mean elimination half-life of ruxolitinib is approximately 3 hours AUC: Mean ruxolitinib Cmax and total exposure (AUC) increased proportionally over a single dose range of 5 to 200 mg.
The plasma protein binding
: 97%, mostly to albumin. Metabolism: Ruxolitinib is metabolized by CYP3A4 and to a lesser extent by CYP2C9.
Excretion
: Following a single oral dose of radio labeled ruxolitinib in healthy adult subjects, elimination was predominately through metabolism with 74% of radioactivity excreted in urine and 22% excretion via feces. Unchanged drug accounted for less than 1% of the excreted total radioactivity.