Drug information of Ruxolitinib

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

Pharmacokinetics

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
 

Drug indications

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

Dosage

Initial Dose:
-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

Maximum dose:
-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

Drug contraindications

None

Side effects

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.

Interactions

Drospirenone , Dorzolamide and timolol , nelfinavir , Tipranavir , Tositumomab , Ibritumomab tiuxetan , Mibefradil , Nicardipine , cobicistat , Delavirdine , Betrixaban , Ramucirumab , Itraconazole , Isoniazid , Imatinib , Posaconazole , Deferiprone , Fluoxetine , Nefazodone , ritonavir , Fosamprenavir , Lopinavir , Indinavir , Voriconazole , Ketoconazole , Clarithromycin , Rivaroxaban , Darunavir , Quinidine , oleandomycin , Pasireotide , Dasatinib , Meningococcal conjugate vaccine

Alerts

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

Infections

• 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.

Hyperlipidemia

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).

 

Pregnancy level

not available

Related drugs

Tofacitinib , vandetanib , Regorafenib , Dabrafenib , Acalabrutinib , Nintedanib , Binimetinib