Alpelisib

INDICATION AND COMBINATION: for HR-positive, HER2-negative advanced breast cancer, patients should be selected on the presence of a PIK3CA mutation in tumour or plasma specimens using a validated test (if not detected in plasma, test tumour tissue if available). Alpelisib should be CO-ADMINISTERED WITH FULVESTRANT; the recommended fulvestrant dose is 500 mg intramuscularly on days 1, 15 and 29 and once monthly thereafter (see the fulvestrant prescribing information). Treatment should be initiated by a physician experienced in the use of anticancer therapies. DOSE REDUCTIONS (SPC Table 1): starting dose 300 mg/day; first reduction 250 mg/day (one 200 mg plus one 50 mg tablet); second reduction 200 mg/day. A maximum of 2 dose reductions is recommended, after which treatment should be permanently discontinued; only one dose reduction is permitted for pancreatitis. MISSED DOSE: may be taken immediately after food within 9 hours of the usual time; after more than 9 hours skip that day's dose and resume at the usual time the next day. VOMITING: do not take an additional dose that day. HYPERGLYCAEMIA (SPC Table 2, based on fasting glucose): above ULN to 160 mg/dL (8.9 mmol/L) — no dose adjustment, initiate or intensify oral antidiabetic treatment; above 160 to 250 mg/dL (8.9 to 13.9 mmol/L) — no dose adjustment, intensify antidiabetic treatment and reduce by one dose level if fasting glucose does not fall to 160 mg/dL (8.9 mmol/L) or less within 21 days; above 250 to 500 mg/dL (13.9 to 27.8 mmol/L) — interrupt, intensify antidiabetic treatment (consider insulin for 1 to 2 days) and IV hydration, resume at the next lower dose level if fasting glucose falls to 8.9 mmol/L or less within 3 to 5 days, permanently discontinue if not controlled within 21 days; above 500 mg/dL (27.8 mmol/L) — interrupt, treat and recheck within 24 hours, permanently discontinue if confirmed above 500 mg/dL after 24 hours. Consultation with a healthcare professional experienced in treating hyperglycaemia is recommended for pre-diabetic patients, fasting glucose above 250 mg/dL (13.9 mmol/L), BMI 30 or more, or age 75 or more, and should always take place for patients with diabetes. RASH (SPC Table 3): Grade 1 or 2 — no dose adjustment, topical corticosteroid and oral antihistamine; Grade 3 — interrupt until improvement to Grade 1 or less then resume at the next lower dose level; Grade 4 — permanently discontinue. Prophylactic oral antihistamine may be considered at initiation. DIARRHOEA OR COLITIS (SPC Table 4): Grade 1 — no adjustment; Grade 2 — interrupt, resume at the same dose level on improvement to Grade 1 or less (next lower level if recurrent Grade 2 or higher); Grade 3 — interrupt then resume at the next lower dose level; Grade 4 — permanently discontinue. OTHER TOXICITIES (SPC Table 5): Grade 1 or 2 — no adjustment; Grade 3 — interrupt then resume at next lower dose level; Grade 4 — permanently discontinue. ELDERLY: no adjustment at 65 years or above; limited data at 75 years or more and especially 85 years or more. HEPATIC: no dose adjustment for mild, moderate or severe impairment (Child-Pugh A, B or C). PAEDIATRIC: safety and efficacy in children aged 0 to 18 years have not been established; no data are available.