Ruxolitinib


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Myelofibrosis, post-essential thrombocythaemia, Myelofibrosis, post-polycythaemia vera, Primary myelofibrosis
Adult: Initial dose is 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. Interrupt dosing if platelet count is <50,000/mm3 or absolute neutrophil count (ANC) <500/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 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 platelet count is <100,000/mm3 and Hb decreases below 12 g/dL. Interrupt dosing if platelet count is <50,000/mm3 or 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.
Special Patient Group
Patients taking strong CYP3A4 inhibitors or dual inhibitors of CY3A4 and CYP2C9 enzymes: Reduce initial unit dose by approx 50 %, given bid.
Renal Impairment
Primary myelofibrosis; Postpolycythaemia vera myelofibrosis; Postessential thrombocythaemia myelofibrosis
CrCl (mL/min) Dosage
15-29 Reduce initial unit dose (based on platelet count) by approx 50%, given bid.
30-59 Reduce initial unit dose (based on platelet count) by approx 50%, given bid.

Polycythemia vera
ESRD patients undergoing haemodialysis: 10 mg as a single dose or 5 mg 12 hrly, given after dialysis session.
CrCl (mL/min) Dosage
15-29 5 mg bid.
30-59 5 mg bid.
Hepatic Impairment
Primary myelofibrosis; Postpolycythaemia vera myelofibrosis; Post-essential thrombocythaemia myelofibrosis
Reduce initial unit dose by approx 50%, given bid.

Polycythemia vera
5 mg bid.
Cách dùng
May be taken with or without food.
Chống chỉ định
Hypersensitivity. 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.
Phản ứng phụ
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.
Metabolism and nutrition disorders: Weight gain, 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.
MonitoringParameters
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).
Food Interaction
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) 1 and 2. JAK 1/2 are tyrosine kinases which mediate the signalling of numbers of cytokines and growth factors that are important for haematopoiesis and immune function. Myelofibrosis and polycythaemia vera are known to be associated with dysregulation of JAK 1/2 thus ruxolitinib modulate the activity of the affected JAK 1/2.
Pharmacokinetics:
Absorption: Rapidly 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 minimally 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
Phân loại ATC
L01XE18 - ruxolitinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. 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 03/04/2018.

Anon. Ruxolitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/04/2018.

Buckingham R (ed). Ruxolitinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/04/2018.

Jakafi Tablet (Incyte Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/04/2018.

Joint Formulary Committee. Ruxolitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/04/2018.

Ruxolitinib. Drugs and Lactation Database (LactMed) [Internet]. Bethesda, MD. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/. Accessed 03/04/2018.

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