Pemigatinib

UK SPC (Pemazyre 13.5 mg tablets, https://www.medicines.org.uk/emc/product/12814/smpc). Therapy should be initiated by a physician experienced in the diagnosis and treatment of biliary tract cancer, and FGFR2 fusion positivity must be confirmed with an appropriate diagnostic test before starting. ADMINISTRATION: take at approximately the same time every day, with or without food; do not crush, chew, split or dissolve the tablets. If a dose is missed by 4 or more hours, or vomiting occurs after taking a dose, do not take an additional dose - resume with the next scheduled dose. PHOSPHATE MANAGEMENT: start a low-phosphate diet when serum phosphate is >5.5 mg/dL and consider adding phosphate-lowering therapy when >7 mg/dL, adjusting until serum phosphate returns to <7 mg/dL; consider discontinuing phosphate-lowering therapy and diet during treatment breaks or if serum phosphate falls below the normal range. DOSE REDUCTION LEVELS: 13.5 mg once daily (14 days on, 7 off) -> first reduction 9 mg once daily (14 on, 7 off) -> second reduction 4.5 mg once daily (14 on, 7 off); discontinue permanently if the patient cannot tolerate 4.5 mg once daily. HYPERPHOSPHATAEMIA: >5.5 to <=7 mg/dL - continue at current dose; >7 to <=10 mg/dL - continue current dose, start phosphate-lowering therapy, monitor serum phosphate weekly, withhold if levels do not return to <7 mg/dL within 2 weeks of starting phosphate-lowering therapy and restart at the same dose when <7 mg/dL, reduce by 1 dose level on recurrence >7 mg/dL; >10 mg/dL - continue current dose with phosphate-lowering therapy and weekly monitoring, withhold if levels continue >10 mg/dL for 1 week and restart 1 dose level lower when <7 mg/dL, permanently discontinue if >10 mg/dL recurs after 2 dose reductions. SEROUS RETINAL DETACHMENT: asymptomatic - continue at current dose with monitoring; moderate decrease in visual acuity - withhold until resolution then resume at the next lower dose level; marked decrease in visual acuity or acuity worse than 20/200 - withhold until resolution then resume 2 dose levels lower; consider permanent discontinuation if it recurs, symptoms persist or examination does not improve. Ophthalmological examination including optical coherence tomography before starting, every 2 months for the first 6 months, every 3 months thereafter, and urgently for any visual symptoms. Elderly: same dose as younger adults. Hepatic impairment: no adjustment for mild or moderate; for severe, reduce 13.5 mg once daily to 9 mg once daily and 9 mg once daily to 4.5 mg once daily. PAEDIATRIC: safety and efficacy in patients under 18 years have not been established, no data available. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol. US labelling additionally describes a continuous (non-intermittent) 13.5 mg once daily regimen for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement - that indication and schedule are not in the fetched UK SPC; verify before use.