Drug information of Ruxolitinib
Ruxolitinib is used in adults to treat myelofibrosis or polycythemia vera, which are bone marrow disorders that affect your body's ability to produce blood cells.
Ruxolitinib is also used to treat graft versus host disease in adults and children at least 12 years old.
Ruxolitinib is usually given after other treatments have failed.
Mechanism of effect
Ruxolitinib is a kinase inhibitor that is selective for the Janus Associated Kinases (JAK) 1 and 2. These kinases are responsible for the mediation of cytokine and growth factor signalling which in turn effect immune function and hematopoiesis. The signalling process involves signal transducers and transcription activators (STAT) which modulate gene expression. Patients with myelofibrosis have abnormal JAK1 and JAK2 activity thus ruxolitinib works to regulate this
Absorption is rapid and is not affected by food
Distribution : Vd: Myelofibrosis: 72 L; Polycythemia vera: 75 L
Metabolism : Hepatic, primarily via CYP3A4 (and minimally CYP2C9); forms active metabolites responsible for 20% to 50% of activity
Excretion :Urine (74%, <1% as unchanged drug); feces (22%, <1% as unchanged drug
Onset of Action: Acute graft-versus-host disease (GVHD): Median time to response: 1.5 weeks (range: 1 to 11 weeks)
Half-Life Elimination :Ruxolitinib: ~3 hours (hepatic impairment: 4.1 to 5 hours); Ruxolitinib + metabolites: ~5.8 hours
Protein Binding: ~97%; primarily to albumin
Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. [Lexicomp] Myeolofibrosis is the proliferation of abnormal bone marrow stem cells which cause fibrosis
-Platelets greater than 200 x 10(9)/L: 20 mg orally twice a day
-Platelets 100 to 200 x 10(9)/L: 15 mg orally twice a day
-Platelets 50 to less than 100 x 10(9)/L: 5 mg orally twice a day
-Starting platelets 100 x 10(9)/L or greater: 25 mg twice a day
-Starting platelets 50 to less than 100 x 10(9)/L: 10 mg twice a day
Commonly reported side effects of ruxolitinib include: anemia, balance impairment, dizziness, headache , meniere's disease, neutropenia, thrombocytopenia, vertigo, and orthostatic dizziness. Other side effects include: weight gain.
InteractionsDrospirenone , Dorzolamide and timolol , nelfinavir , Tofacitinib , Tipranavir , Tositumomab , Ibritumomab tiuxetan , Mibefradil , Nicardipine , cobicistat , Delavirdine , Betrixaban , Ramucirumab , Itraconazole , Isoniazid , Imatinib , Posaconazole , Deferiprone , Fluoxetine , Quinidine , Nefazodone , ritonavir , Fosamprenavir , Lopinavir , Indinavir , Voriconazole , Ketoconazole , Clarithromycin , Rivaroxaban , Atazanavir , Darunavir , oleandomycin , Pasireotide , Dasatinib , Meningococcal conjugate vaccine
Nonmelanoma skin cancers reporrted including basal cell, squamous cell, and Merkel cell carcinoma
- Perform CBC before initiating therapy and monitor as clinically indicated and dosing adjusted as required
- Patients with platelet counts <200 x10^9/L at the start of therapy are more likely to develop thrombocytopenia during treatment
- Thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily withholding dose (see Adult Dosing); if clinically indicated, platelet transfusions may be administered
- Anemia may require blood transfusions; dose modifications may also be considered
- Neutropenia (ANC <0.5 x10^9/L) was generally reversible and was managed by temporarily withholding dose
- Assess for the risk of developing serious bacterial, mycobacterial, fungal, and viral infections
- Active serious infections should have resolved before starting therapy
- Tuberculosis (TB) infection has been reported; before initiating, evaluate patients for TB risk factors, and those at higher risk should be tested for latent infection.
reatment has been associated with increases in lipid parameters including total cholesterol, low density lipoprotein, and triglycerides; assess lipid parameters approximately 8-12 weeks following initiation of therapy; monitor according to clinical guidelines for management of hyperlipidemia.
Pregnancy:There are no studies with use in pregnant women to inform drug-associated risks
Points of recommendation
Tell your doctor if you have ever had:
- any type of chronic infection;
- kidney disease (or if you are on dialysis);
- liver disease(especially hepatitis B);
- skin cancer; or
- high cholesterolor triglycerides (types of fat in the blood).