Luspatercept

US label sections 2.1 and 2.2: the recommended starting dose is 1 mg/kg once every 3 weeks by subcutaneous injection in both indications. Review the patient's haemoglobin and transfusion record before each dose, and if an RBC transfusion occurred before dosing use the pre-transfusion haemoglobin for dose evaluation. If a planned administration is delayed or missed, administer as soon as possible and continue dosing as prescribed with at least 3 weeks between doses. BETA THALASSAEMIA TITRATION (Table 1): if after at least 2 consecutive doses (6 weeks) at 1 mg/kg there is no reduction in RBC transfusion burden, increase to 1.25 mg/kg every 3 weeks; if after 3 consecutive doses (9 weeks) at 1.25 mg/kg there is still no reduction in transfusion burden, discontinue. Do not increase beyond the maximum of 1.25 mg/kg. MDS TITRATION (Tables 3 and 4): do not increase the dose more frequently than every 6 weeks (2 doses) or beyond the maximum of 1.75 mg/kg; for ESA-naive MDS make dose adjustments to maintain haemoglobin within the target range of 10 g/dL to 12 g/dL, and for ESA-refractory or intolerant MDS increase the dose if the patient is not RBC transfusion-free. If on dose reduction the patient loses response (requires a transfusion) or haemoglobin drops by 1 g/dL or more in 3 weeks without transfusion, increase by one dose level, waiting a minimum of 6 weeks between increases. DOSE MODIFICATIONS FOR HIGH OR RAPIDLY RISING HAEMOGLOBIN: if the predose haemoglobin is 11.5 g/dL or greater in the absence of transfusion, interrupt treatment and restart at the same dose when haemoglobin is no more than 11 g/dL; if haemoglobin increases by more than 2 g/dL within 3 weeks in the absence of transfusion, reduce 1.25 mg/kg to 1 mg/kg, 1 mg/kg to 0.8 mg/kg, or 0.8 mg/kg to 0.6 mg/kg, and discontinue if the current dose is already 0.6 mg/kg. TOXICITY (Table 2): discontinue for Grade 3 or 4 hypersensitivity reactions, and for extramedullary haematopoietic masses causing serious complications; for other Grade 3 or 4 adverse reactions interrupt treatment and, when the reaction resolves to no more than Grade 1, restart at the next lower dose level — discontinue if the dose delay is greater than 15 consecutive weeks. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established and, based on findings in juvenile animals, luspatercept is not recommended for use in paediatric patients — verify against a children's formulary. SOURCE: no UK SPC was fetched in this bundle — this draft is distilled from the US prescribing information and must be verified against the UK SPC.