Fostamatinib

SOURCE: UK SPC for Tavlesse 100 mg film-coated tablets (eMC §4.2). Treatment should be initiated and remain under the supervision of a physician experienced in the treatment of haematological diseases. Dosing must be individualised to the platelet count — use the lowest dose that achieves and maintains a platelet count of at least 50,000/microlitre. DISCONTINUATION: stop after 12 weeks of therapy if the platelet count does not increase to a level sufficient to avoid clinically important bleeding. MISSED DOSE: take the next dose at its regularly scheduled time. DOSE REDUCTION SCHEDULE (table 1): 300 mg/day given as 150 mg AM + 150 mg PM; 200 mg/day as 100 mg AM + 100 mg PM; 150 mg/day as 150 mg once daily in the morning; 100 mg/day as 100 mg once daily in the morning; if further reduction below 100 mg/day is required, discontinue. MONITORING: clinical haematology, blood pressure and liver function tests regularly — blood pressure every two weeks until stable then monthly; LFTs monthly; CBC including platelets monthly until a stable count of at least 50,000/microlitre, then CBC including neutrophils regularly. DOSE MODIFICATIONS (table 2): HYPERTENSION — stage 1 (systolic 130–139 or diastolic 80–89 mmHg): start or increase antihypertensive therapy in patients with increased cardiovascular risk and, if the BP target is not met after 8 weeks, reduce to the next lower daily dose; stage 2 (systolic at least 140 or diastolic at least 90 mmHg): start or increase antihypertensive therapy and, if BP remains 140/90 mmHg or higher for more than 8 weeks, reduce to the next lower daily dose; if BP remains 160/100 mmHg or higher for more than 4 weeks despite aggressive therapy, interrupt or discontinue; hypertensive crisis (systolic over 180 and/or diastolic over 120 mmHg): interrupt or discontinue. HEPATOTOXICITY — AST/ALT 3 to less than 5 x ULN: if symptomatic interrupt and recheck LFTs every 72 hours, resuming at the next lower daily dose once ALT/AST are below 1.5 x ULN and total bilirubin remains below 2 x ULN; AST/ALT 5 x ULN or higher with total bilirubin below 2 x ULN: interrupt and recheck every 72 hours, resume at the next lower daily dose on recovery, and discontinue if AST/ALT persist at 5 x ULN or higher for 2 weeks or more; AST/ALT 3 x ULN or higher with total bilirubin above 2 x ULN: discontinue; isolated elevated unconjugated (indirect) bilirubin without other LFT abnormality: continue with frequent monitoring (may be due to UGT1A1 inhibition). DIARRHOEA — manage with supportive measures early; if Grade 3 or above, interrupt and resume at the next lower daily dose once improved to Grade 1. NEUTROPENIA — if ANC falls below 1.0 x 10^9/L and remains low after 72 hours, interrupt until ANC is above 1.5 x 10^9/L, then resume at the next lower daily dose. HEPATIC IMPAIRMENT: should not be used in severe hepatic impairment; monitor liver function throughout therapy in mild or moderate impairment and adjust the regimen as required. ELDERLY: no dose adjustment necessary. PAEDIATRIC: fostamatinib should not be used in children and adolescents under 18 years of age because of adverse reactions on actively growing bones observed in nonclinical studies — no paediatric dose exists; verify any alternative against a children's formulary.