Ruxolitinib


Thông tin thuốc gốc
Chỉ định và Liều dùng
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.
Nhóm bệnh nhân đặc biệt
Patients taking strong CYP3A4 inhibitors or dual inhibitors of CY3A4 and CYP2C9 enzymes: Reduce total daily dose by approx 50%.
Suy thận
 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. 

Suy gan
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.
Cách dùng
May be taken with or without food.
Chống chỉ định
Pregnancy and lactation.
Thận trọng
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.
Tác dụng không mong muốn
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.
Thông tin tư vấn bệnh nhân
This drug may cause dizziness, if affected, do not drive or operate machinery.
Chỉ số theo dõi
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.
Quá liều
Symptoms: Myelosuppression (e.g. anaemia, leucopenia, thrombocytopenia). Management: Supportive treatment.
Tương tác
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).
Tương tác với thức ăn
Decrease plasma concentration with St. John’s wort. Increased plasma concentration with grapefruit or grapefruit juice.
Tác dụng
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).
Đặc tính

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)

Bảo quản
Store between 20-25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
Phân loại MIMS
Liệu pháp nhắm trúng đích
Phân loại ATC
L01EJ01 - ruxolitinib ; Belongs to the class of Janus-associated kinase (JAK) inhibitors. Used in the treatment of cancer.
Tài liệu tham khảo
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.

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