Avapritinib

Source: UK SPC (eMC) §4.2 for AYVAKYT 100 mg film-coated tablets (https://www.medicines.org.uk/emc/product/15581/smpc). Therapy should be initiated by a healthcare professional experienced in the diagnosis and treatment of the conditions for which avapritinib is indicated. PATIENT SELECTION (GIST): selection for treatment of unresectable or metastatic GIST harbouring the PDGFRA D842V mutation should be based on a validated test method. ADvSM RESTRICTION: treatment is not recommended in patients with a platelet count of less than 50 x 10^9/L. DOSE REDUCTIONS FOR ADVERSE REACTIONS (Table 1) — GIST (starting dose 300 mg): first reduction 200 mg once daily, second reduction 100 mg once daily. AdvSM (starting dose 200 mg): first reduction 100 mg once daily, second reduction 50 mg once daily, third reduction 25 mg once daily. DOSE MODIFICATIONS (Table 2): intracranial haemorrhage, any grade — permanently discontinue. Cognitive effects Grade 1 — continue at the same dose, reduce, or interrupt until improvement to baseline or resolution, then resume at the same or a reduced dose; Grade 2 or 3 — interrupt until improved to baseline, Grade 1 or resolution, then resume at the same or a reduced dose; Grade 4 — permanently discontinue. Other adverse reactions Grade 3 or 4 — interrupt until less than or equal to Grade 2, then resume at the same or a reduced dose if warranted. AdvSM thrombocytopenia below 50 x 10^9/L — interrupt dosing until the platelet count is at least 50 x 10^9/L, then resume at a reduced dose; if the platelet count does not recover above 50 x 10^9/L, consider platelet support. CYP3A: concomitant use with strong or moderate CYP3A inhibitors should be avoided; if use with a moderate CYP3A inhibitor cannot be avoided, reduce the starting dose from 300 mg to 100 mg once daily (GIST) or from 200 mg to 50 mg once daily (AdvSM). MISSED DOSES: make up a missed dose unless the next scheduled dose is within 8 hours, in which case omit it and resume with the next scheduled dose; if vomiting occurs after a dose, do not take an additional dose but continue with the next scheduled dose. ELDERLY: no dose adjustment for patients aged 65 years and above. HEPATIC IMPAIRMENT: no dose adjustment for mild or moderate impairment; for severe impairment (Child-Pugh Class C) reduce the starting dose from 300 mg to 200 mg once daily (GIST) and from 200 mg to 100 mg once daily (AdvSM). PAEDIATRIC: safety and efficacy in children aged 0 to 18 years have not yet been established; no data are available. §4.5 was not present in the fetched bundle — the interactions listed are those named within §4.2 and §4.4.