Ruxolitinib


Generic Medicine Info
Indications and Dosage
Oral
Post-essential thrombocythaemia myelofibrosis, Post-polycythaemia vera myelofibrosis, Primary myelofibrosis
Adult: Initial dose (based on platelet count): >200,000/mm3: 20 mg bid; 100,000-200,000/mm3: 15 mg bid; 50,000-<100,000/mm3: 5 mg bid. Titrate doses based on efficacy and tolerability. Discontinue if platelet count is <50,000/mm3 or absolute neutrophil count (ANC) <500/mm3. Dose may be reduced if platelet is <100,000/mm3. If response is insufficient and blood counts are adequate, doses may be increased by up to 5 mg bid. Max: 25 mg bid. Initial dose may be increased after the 1st 4 weeks of treatment and thereafter no more frequently than every 2 weeks. Discontinue if there is no improvement in symptoms or reduction in spleen size after 6 months.

Oral
Polycythemia vera
Adult: In patients who are resistant or intolerant to hydroxyurea: Initially, 10 mg bid. Titrate doses based on efficacy and tolerability. Dose may be reduced if Hb decreases below 12 g/dL. Interrupt dosing if Hb <8 g/dL. If response is insufficient and blood counts are adequate, doses may be increased by up to 5 mg bid. Max: 25 mg bid. Initial dose may be increased after the 1st 4 weeks of treatment and thereafter no more frequently than every 2 weeks.

Oral
Steroid-refractory acute graft-versus-host disease
Adult: Initially, 5 mg bid, may increase to 10 mg bid after at least 3 days if platelet and neutrophil counts have not decreased by at least 50% from baseline. Gradually reduce dose after 6 months by 1 dose level approx every 8 weeks in responsive patients who have stopped corticosteroid treatment. Retreatment may be needed if signs/symptoms recur during or after dose reduction. Dosage may be modified based on blood parameters result (see detailed product guideline).
Child: ≥12 years Same as adult dose.
Special Patient Group
Patients taking strong CYP3A4 inhibitors or dual inhibitors of CY3A4 and CYP2C9 enzymes: Reduce total daily dose by approx 50%.
Renal Impairment
 Primary myelofibrosis; Post-polycythaemia vera myelofibrosis; Post-essential thrombocythaemia myelofibrosis:
 CrCl (mL/min)  Dosage
 <30 Reduce initial dose (based on platelet count) by approx 50%, given bid.

Polycythemia vera
ESRD patients undergoing haemodialysis: 10 mg as a single dose or in 2 divided dose 12 hourly, given after dialysis session.

 CrCl (mL/min)  Dosage
 <30  5 mg bid. 

Steroid refractory, acute graft versus host disease 
ESRD patients undergoing haemodialysis: 5 mg as a single dose or in 2 divided dose 12 hourly, given after dialysis session.

 CrCl (mL/min)  Dosage
 15-29  5 mg once daily. 
 30-59  5 mg once daily. 

Hepatic Impairment
Primary myelofibrosis; Post-polycythaemia vera myelofibrosis; Post-essential thrombocythaemia myelofibrosis
Reduce initial dose by approx 50%, given bid. Subsequent dose is adjusted based on individual safety and efficacy.

Polycythemia vera; Steroid refractory, acute graft versus host disease
Reduce initial dose by approx 50%. Subsequent dose is adjusted based on individual safety and efficacy.
Administration
May be taken with or without food.
Contraindications
Pregnancy and lactation.
Special Precautions
Patient with TB or risk of TB, chronic hepatitis B virus infection. Patients taking strong CYP3A4 inhibitors or dual inhibitors of CY3A4 and CYP2C9 enzymes (e.g. fluconazole). Hepatic and moderate to severe renal impairment.
Adverse Reactions
Significant: Anaemia, thrombocytopenia, neutropenia; serious bacterial, mycobacterial, fungal, and viral infections (e.g. TB, herpes zoster, pneumonia, UTI); increased cholesterol and triglycerides, non-melanoma skin cancers (e.g. basal cell, squamous cell, Merkel cell carcinoma), progressive multifocal leukoencephalopathy (PML).
Cardiac disorders: Dyspnoea.
Gastrointestinal disorders: Diarrhoea, abdominal pain, constipation, nausea, flatulence, vomiting, gastrointestinal bleeding.
General disorders and administration site conditions: Fatigue, weakness.
Investigations: Increased ALT/AST, weight gain.
Metabolism and nutrition disorders: Hypercholesterolaemia, hypertriglyceridaemia, oedema.
Musculoskeletal and connective tissue disorders: Muscle spasm.
Nervous system disorders: Dizziness, headache, intracranial bleeding.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, cough, epistaxis.
Skin and subcutaneous tissue disorders: Bruising.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC with differential (prior to therapy and every 2-4 weeks until doses are stabilised, then as clinically indicated), lipid parameters, hepatic and renal function, HBV-DNA titer; signs and symptoms of infections. Evaluate patients for presence of active or latent TB prior to treatment.
Overdosage
Symptoms: Myelosuppression (e.g. anaemia, leucopenia, thrombocytopenia). Management: Supportive treatment.
Drug Interactions
Increased plasma concentration with strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (e.g. ciprofloxacin, erythromycin, amprenavir, atazanavir, diltiazem, cimetidine). Decreased plasma concentration with CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin). May increase plasma concentration of substances transported by P-glycoprotein and breast cancer resistance protein (e.g. dabigatran, ciclosporin, rosuvastatin, digoxin).
Food Interaction
Decrease plasma concentration with St. John’s wort. Increased plasma concentration with grapefruit or grapefruit juice.
Action
Description: Ruxolitinib is a selective inhibitor of Janus Associated Kinases (JAKs), JAK1 and JAK2 which mediate the signalling of cytokines and growth factors that are important for haematopoiesis and immune function. In myelofibrosis and polycythaemia vera are known to be associated with dysregulation of JAK 1/2. JAK mediated signalling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, thus leading to modulation of gene expression. JAK-STAT signalling is involved with the regulation of the development, proliferation, and activation of immune cell types important to GVHD pathogenesis.
Onset: Acute graft-versus-host disease: 1.5 weeks (median time to response).
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: Within 1-2 hours.
Distribution: Volume of distribution: Myelofibrosis: 72 L; Polycythemia vera: 75 L. Plasma protein binding: Approx 97%, mainly to albumin.
Metabolism: Metabolised in the liver mainly by CYP3A4, and to lesser extent by CYP2C9 enzymes.
Excretion: Mainly via urine (74%, <1% as unchanged drug); faeces (22%, <1% as unchanged drug). Elimination half-life: Approx 3 hours (ruxolitinib); approx 5.8 hours (ruxolitinib + metabolites).
Chemical Structure

Chemical Structure Image
Ruxolitinib

Source: National Center for Biotechnology Information. PubChem Database. Ruxolitinib, CID=25126798, https://pubchem.ncbi.nlm.nih.gov/compound/Ruxolitinib (accessed on Jan. 23, 2020)

Storage
Store between 20-25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Targeted Cancer Therapy
ATC Classification
L01EJ01 - ruxolitinib ; Belongs to the class of Janus-associated kinase (JAK) inhibitors. Used in the treatment of cancer.
References
Anon. Ruxolitinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 03/09/2020.

Anon. Ruxolitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/09/2020.

Buckingham R (ed). Ruxolitinib Phosphate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/09/2020.

Jakafi Tablet (Incyte Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/09/2020.

Jakafi Tablets (DSM Pharmaceuticals, Inc.). U.S. FDA. https://www.fda.gov/. Accessed 03/09/2020.

Joint Formulary Committee. Ruxolitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/09/2020.

Disclaimer: This information is independently developed by MIMS based on Ruxolitinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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