Imatinib (Specialist drug)

Source: UK SPC (eMC) 4.2 for Glivec 100 mg film-coated tablets (https://www.medicines.org.uk/emc/product/7779/smpc). VERBATIM: 'The recommended dosage of Glivec is 400 mg/day for adult patients in chronic phase CML.' Therapy must be initiated by a physician experienced in haematological malignancies and malignant sarcomas. Adult doses by indication (SPC 4.2): chronic phase CML 400 mg/day; accelerated phase CML 600 mg/day; blast crisis 600 mg/day; Ph+ ALL 600 mg/day (with chemotherapy in induction/consolidation/maintenance, or as monotherapy in relapsed/refractory disease); MDS/MPD 400 mg/day; HES/CEL 100 mg/day (may increase to 400 mg if insufficient response and no adverse reactions); GIST (unresectable and/or metastatic) 400 mg/day; adjuvant GIST after resection 400 mg/day (trial duration 36 months); DFSP 800 mg/day. Dose increases from 400 mg to 600 mg or 800 mg (chronic phase), or from 600 mg to a maximum of 800 mg (accelerated phase/blast crisis), may be considered in the absence of severe adverse reactions and severe non-leukaemia-related cytopenias where there is disease progression, failure of haematological response after at least 3 months, failure of cytogenetic response after 12 months, or loss of a previous response - monitor closely after escalation. Non-haematological toxicity: withhold until resolved; if bilirubin >3 x IULN or transaminases >5 x IULN, withhold until bilirubin <1.5 x IULN and transaminases <2.5 x IULN, then resume at a reduced daily dose (400 to 300 mg, 600 to 400 mg, or 800 to 600 mg). Haematological toxicity: see SPC Table for stop/resume thresholds by indication (e.g. chronic phase CML/MDS/MPD/GIST at 400 mg - stop until ANC >=1.5 x 10^9/l and platelets >=75 x 10^9/l, resume at previous dose; on recurrence resume at 300 mg). Tablets may be dispersed in still water or apple juice (approx. 50 ml per 100 mg tablet, 200 ml per 400 mg tablet) if swallowing is difficult. Hepatic impairment (mild, moderate or severe): give the minimum recommended dose of 400 mg daily; reduce if not tolerated. Elderly: no specific dose recommendation necessary. PAEDIATRIC (SPC 4.2, by body surface area, not per kg): 340 mg/m2 daily for children with chronic phase and advanced phase CML (not to exceed a total dose of 800 mg), given once daily or split into two doses; may be increased to 570 mg/m2 daily (not exceeding 800 mg total) under the same escalation criteria as adults; for Ph+ ALL in children 340 mg/m2 daily (not to exceed a total dose of 600 mg). No experience below 2 years of age in CML and below 1 year in Ph+ ALL; paediatric dose reduction step is 340 to 260 mg/m2/day. No posology recommendation can be made for children with MDS/MPD, DFSP, GIST or HES/CEL. Verify all paediatric dosing against a children's formulary and local protocol. NOTE: source SPC sections 4.4/4.8 were truncated at the fetch limit.