Bosutinib


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Chronic phase Philadelphia chromosome positive chronic myelogenous leukaemia
Adult: In patient with newly-diagnosed case: 400 mg once daily, continue until disease progression. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Oral
Accelerated phase Philadelphia chromosome positive chronic myelogenous leukaemia, Blast phase Philadelphia chromosome positive chronic myelogenous leukaemia, Chronic phase Philadelphia chromosome positive chronic myelogenous leukaemia
Adult: With resistance to prior treatment or intolerance to other therapy: 500 mg once daily, continue until disease progression. May increase dose to 600 mg once daily in patients who have incomplete haematological response by week 8 or an incomplete cytogenetic response by week 12. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal Impairment
Chronic phase, accelerated phase, and blast phase Philadelphia chromosome positive chronic myelogenous leukaemia with resistance to prior treatment or intolerance to other therapy:
 CrCl (mL/min) Dosage 
 <30  300 mg once daily.
 30-50  400 mg once daily.

Newly-diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia:
 CrCl (mL/min  Dosage
 <30   200 mg once daily.
 30-50   300 mg once daily.
Hepatic Impairment
200 mg once daily.
Cách dùng
Film-Coated Tab: Should be taken with food. Swallow whole, do not cut/crush/break.
Chống chỉ định
Lactation.
Thận trọng
Patient with gastrointestinal or cardiac disorders, history of pancreatitis. Renal and hepatic impairment. Elderly. Pregnancy.
Phản ứng phụ
Significant: Thrombocytopenia, anaemia, neutropenia, leukopenia, fluid retention/oedema, diarrhoea, abdominal pain, nausea, vomiting; increased serum transaminase ALT/AST, decreased glomerular filtration rate, increased serum lipase; infections; renal impairment; severe skin reactions (e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis); tumour lysis syndrome; hepatitis B reactivation. Rarely, hypersensitivity reactions (e.g. anaphylaxis, anaphylactic shock), acute pancreatitis, QT prolongation.
Cardiac disorders: Pericardial effusion, chest pain.
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Gastritis, gastrointestinal haemorrhage.
General disorders and administration site conditions: Pyrexia, asthenia, fatigue.
Metabolism and nutrition disorders: Decreased appetite, dehydration, hyperkalaemia, hypophosphataemia.
Musculoskeletal and connective tissue disorders: Arthralgia, back pain.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Pleural effusion, respiratory tract infection, dyspnoea, cough, nasopharyngitis.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Hypertension.
Potentially Fatal: Acute hepatic failure or fulminant hepatitis.
MonitoringParameters
Monitor CBC with differential and platelet count weekly during the 1st month, then monthly thereafter or as clinically indicated; LFT monthly for the first 3 months or as clinically indicated; renal function test at baseline and throughout the therapy. Monitor for signs and symptoms of gastrointestinal toxicity (e.g. diarrhoea episodes); fluid retention (e.g. oedema, weight gain).
Tương tác
Increased plasma concentration with CYP3A inhibitors (e.g. atazanavir, clarithromycin, itraconazole, nefazodone, verapamil, aprepitant, crizotinib). Decreased plasma concentration with CYP3A inducers (e.g. carbamazepine, phenytoin, rifampicin); proton pump inhibitors (e.g. omeprazole). May enhance QT prolonging effect of anti- arrhythmic drugs (e.g. amiodarone, quinidine).
Food Interaction
Increased plasma concentration with grapefruit or grapefruit juice. Decreased plasma concentration with St. John’s wort.
Tác dụng
Description: Bosutinib is a tyrosine kinase inhibitor that inhibits the abnormal BCR-ABL kinase that promotes chronic myeloid leukaemia (CML). It also inhibits receptor kinases for Src family kinases (e.g. Src, Lyn, Hck). It has minimal effect against non-specific targets c-Kit and platelet-derived growth factor (PDGF) receptor.
Onset: Cytogenic response: 12.3 weeks.
Pharmacokinetics:
Absorption: Slowly absorbed from the gastrointestinal tract. Food, particularly high fat meal, increases the rate and extent of absorption. Bioavailability: 34%. Time to peak plasma concentration: 4-6 hours.
Distribution: Extensively distributed to extra vascular spaces. Plasma protein binding: 94%. Volume of distribution: Approx. 1,230 L
Metabolism: Metabolised in the liver by CYP3A4 enzyme to inactivate metabolites oxydechlorinated (M2) bosutinib, N-desmethylated (M5) bosutinib, and bosutinib N-oxide (M6).
Excretion: Via faeces (approx 93%); urine (approx 3%). Half-life: Approx 22-27 hours.
Đặc tính

Chemical Structure Image
Bosutinib

Source: National Center for Biotechnology Information. PubChem Database. Bosutinib, CID=5328940, https://pubchem.ncbi.nlm.nih.gov/compound/Bosutinib (accessed on Jan. 21, 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
L01EA04 - bosutinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.
References
Anon. Bosutinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/03/2019.

Bosulif Tablet, Film Coated (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/03/2019.

Buckingham R (ed). Bosutinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/03/2019.

Joint Formulary Committee. Bosutinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/03/2019.

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