Fedratinib (Specialist drug)

PLATELET THRESHOLD: the recommended 400 mg once daily dose applies to patients with a baseline platelet count of 50 x 10^9/L or greater. MANDATORY CO-PRESCRIPTION: all patients should receive prophylaxis with thiamine 100 mg orally daily during treatment. Conduct baseline thiamine (vitamin B1) testing before initiation and do not start fedratinib in patients with thiamine deficiency — if levels are low, replete thiamine before starting. If Wernicke's encephalopathy is suspected, immediately discontinue fedratinib and start parenteral thiamine, monitoring until symptoms resolve or improve and thiamine levels normalise. SWITCHING FROM RUXOLITINIB: patients on ruxolitinib before initiation must taper and discontinue it according to the ruxolitinib prescribing information. MISSED DOSE: if a dose is missed, take the next scheduled dose the following day. DOSE MODIFICATION FOR STRONG CYP3A4 INHIBITORS: reduce to 200 mg once daily; when the inhibitor is discontinued, increase to 300 mg once daily for the first two weeks, then to 400 mg once daily thereafter as tolerated. DOSE MODIFICATION FOR ADVERSE REACTIONS: Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with active bleeding, or Grade 4 neutropenia — interrupt until resolved to Grade 2 or lower or baseline, then restart at 100 mg daily below the last given dose; consider dose reductions in patients who become transfusion-dependent. Grade 3 or higher nausea, vomiting or diarrhoea not responding to supportive measures within 48 hours; Grade 3 or higher ALT, AST or bilirubin; or Grade 3 or higher other non-haematologic toxicity — interrupt until resolved to Grade 1 or lower or baseline, then restart at 100 mg daily below the last given dose. For hepatic toxicity, monitor ALT, AST and bilirubin (total and direct) more frequently after the dose reduction, and discontinue if a Grade 3 or higher elevation recurs. Discontinue fedratinib in patients unable to tolerate a dose of 200 mg daily. MONITORING: obtain thiamine level, full blood count with platelets, creatinine and BUN, hepatic panel, and amylase and lipase before starting, periodically during treatment, and as clinically indicated. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established. GERIATRIC: no overall differences in safety or effectiveness were observed in patients over 65 or over 75. SOURCE: no UK SPC was fetched in this bundle; this draft is distilled from the US INREBIC prescribing information and must be verified against the UK SPC. Fetched sections were truncated at the source-fetch limit.