Ivosidenib (Specialist drug)

Source: US FDA prescribing information for TIBSOVO (Servier Pharmaceutical LLC, label date 2025-12-22, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=190606ed-cb7f-411b-8548-cc2f98e57819). NO UK eMC SPC WAS IN THE SOURCE BUNDLE - dose is taken from US labelling and must be verified against the UK SPC before publication. VERBATIM: 'The recommended dosage of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity.' PATIENT SELECTION: select patients on the basis of an IDH1 mutation. In AML or MDS without progression or unacceptable toxicity, continue for a minimum of 6 months to allow time for clinical response. NEWLY DIAGNOSED AML (combination regimen): start on Cycle 1 Day 1 in combination with azacitidine 75 mg/m2 subcutaneously or intravenously once daily on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle - refer to the azacitidine prescribing information. MISSED/VOMITED DOSE: if a dose is vomited do not give a replacement, wait for the next scheduled dose; if a dose is missed or not taken at the usual time, give it as soon as possible and at least 12 hours before the next scheduled dose, then return to the normal schedule - never give 2 doses within 12 hours. MONITORING: ECG before starting, then at least weekly for the first 3 weeks and at least monthly thereafter; blood counts and chemistries before starting, at least weekly for the first month, every other week for the second month and monthly thereafter in AML/MDS; creatine phosphokinase weekly for the first month. DOSE MODIFICATION: differentiation syndrome - give systemic corticosteroids with haemodynamic monitoring until symptoms resolve and for a minimum of 3 days; interrupt if severe signs/symptoms persist beyond 48 hours after starting corticosteroids and resume when improved to grade 2 or lower. Non-infectious leukocytosis (WBC >25 x 10^9/L or an absolute rise >15 x 10^9/L from baseline) - start hydroxyurea (and leukapheresis if indicated); interrupt if not improved with hydroxyurea and resume at 500 mg daily once resolved. QTc >480 to 500 msec - correct electrolytes, review QT-prolonging co-medication, interrupt and restart at 500 mg once daily once QTc is <=480 msec. QTc >500 msec - interrupt and resume at a reduced dose of 250 mg once daily when QTc returns to within 30 msec of baseline or <=480 msec; re-escalation to 500 mg may be considered if an alternative cause is identified. QTc prolongation with signs/symptoms of life-threatening arrhythmia, or Guillain-Barre syndrome - discontinue permanently. Other grade 3 or higher reactions - as monotherapy in AML/MDS: interrupt until resolved to grade 2 or lower then resume at 250 mg once daily, increasing to 500 mg if toxicity resolves to grade 1 or lower, and discontinue if grade 3 or higher recurs; in cholangiocarcinoma, or in AML with azacitidine: interrupt until resolved to grade 1 or lower or baseline, then resume at 500 mg daily (grade 3) or 250 mg daily (grade 4), with further reductions/discontinuation on recurrence. STRONG CYP3A4 INHIBITORS: if coadministration is unavoidable, reduce the dose to 250 mg once daily. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established, so paedDose is null; verify any under-18 use against a children's formulary and local protocol. NOTE: source label sections were truncated at the fetch limit.