Company: Pfizer Healthcare Ireland.
Legal category: Prescription. High Tech. Sport permitted.
Active ingredient: Bosutinib (as monohydrate) 100mg, 500mg.
Description: Yellow or red oval biconvex, film-coated tablet marked Pfizer on one side and 100 or 500 on reverse, respectively.
Presentation: 100mg-28; 500mg-28. Prices on request.
Indications: Treatment of chronic phase, accelerated phase, and blast phase Philadelphia chromosome positive chronic myelogenous leukaemia (Ph+ CML) in adults, previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.
Pharmacology: Bosutinib belongs to a class of drugs known as kinase inhibitors. It inhibits the abnormal Bcr-Abl kinase that promotes CML. Bosutinib is also an inhibitor of Src family kinases including Src, Lyn and Hck; it minimally inhibits PDGF receptor and c-Kit. In in vitro studies, bosutinib inhibits proliferation and survival of established CML cell lines, Ph+ acute lymphoblastic leukaemia cell lines, and patient-derived primary primitive CML cells.
Dosage: Adult: Usually, 500mg once daily with food. Dose may be increased to 600mg (maximum) once daily in patients who do not experience severe or persistent moderate-adverse reactions, under any of the following circumstances; failure to achieve complete haematologic response by week 8, or failure to achieve complete cytogenetic response by week 12. If clinically significant moderate or severe non-haematoloical toxicity develops, interrupt therapy and resume at 400mg once daily once toxicity has resolved. If clinically appropriate, consider re-escalation to 500mg once daily. If elevations in liver transaminases > 5 x ULN occur, interrupt therapy until recovery to ≤ 2.5 x ULN and resume at 400mg once daily. If recovery takes longer than 4 weeks, consider discontinuation. If transaminase elevations ≥ 3 x ULN occur concurrently with bilirubin elevations >2 x ULN and alkaline phosphatase <2 x ULN, discontinue. For NCI CTCAE Grade 3-4 diarrhoea, interrupt and resume at 400mg once daily upon recovery to grade ≤1. If severe or persistent neutropenia (absolute neutrophil count (ANC) < 1.0 x 109/L) and/or thrombocytopenia (platelets <50 x 109/L) occur, hold therapy until ANC ≥ 1.0x 109/L and platelets ≥ 50 x 109/L. Resume therapy at the same dose if recovery occurs within 2 weeks. If blood counts remain low for > 2 weeks, reduce dose by 100mg and resume therapy. If cytopoenia recurs, reduce dose by 100mg upon recovery and resume therapy. Elderly: Caution. Children: Under 18 years, safety and efficacy not established.
Contraindications: Hypersensitivity to the active substance or any of the excipients. Hepatic impairment. Pregnancy (limited data), lactation.
Special precautions: Renal impairment (patients with serum creatinine >1.5 x ULN, not studied). Increasing exposure in patients with moderate renal impairment observed. Perform liver function tests prior to treatment initiation and monthly for the first three months of treatment, and as clinically indicated. Caution: Recent or ongoing clinically significant gastrointestinal disorder, history of pancreatitis (if accompanied by abdominal symptoms, interrupt therapy and exclude pancreatitis), history of or predisposition for QTc prolongation, uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia. Monitor QTc interval and perform baseline ECG before therapy initiation and as clinically indicated. Correct hypokalaemia or hypomagnesaemia prior to initiation and monitor periodically during therapy. Withhold temporarily, reduce dose and/or discontinue if: Serum transaminases (ALT/AST) become elevated, or fluid retention including pericardial effusion, pleural effusion and pulmonary oedema, or myelosuppression occur. Perform complete blood counts weekly for the first month and then monthly thereafter, or as clinically indicated. May predispose patients to bacterial, fungal, viral or protozoan infections.
Drug interactions: Avoid: Domperidone, potent or moderate CYP3A inhibitors/inducers, grapefruit products, other foods known to inhibit CYP3A. Caution: Drugs known to prolong the QT interval, mild CYP3A inhibitors/inducers, proton pump inhibitors, P-glycoprotein substrates.
Adverse drug reactions: Respiratory tract infection, pneumonia, influenza, bronchitis, nasopharyngitis, thrombocytopenia, neutropenia, anaemia, leukopenia, febrile neutropenia, drug hypersensitivity, decreased appetite, dehydration, hyperkalaemia, hypophosphataemia, headache, dizziness, dysgeusia, pericardial effusion, prolonged electrocardiogram QT, cough, dyspnoea, pleural effusion, GI disorders, increased ALT/AST, hepatotoxicity, abnormal hepatic function, increased blood bilirubin, increased gamma-glutamyltransferase, rash, urticaria, acne, pruritus, arthralgia, myalgia, back pain, renal failure, pyrexia, oedema, fatigue, chest pain, pain, increased lipase, increased blood creatinine, increased blood amylase, increased blood creatine phosphokinase.
Full prescribing information and references available from Pfizer Healthcare Ireland. Telephone: 1800 633 363.