Brigatinib

INITIATION: treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products, and ALK-positive NSCLC status must be confirmed with a validated ALK assay before starting. RE-STARTING: if brigatinib is interrupted for 14 days or longer for reasons other than adverse reactions, resume at 90 mg once daily for 7 days before increasing to the previously tolerated dose. MISSED DOSE OR VOMITING: do not give an additional dose; take the next dose at the scheduled time. DOSE REDUCTION LEVELS (SPC Table 1): from 90 mg once daily (first 7 days) reduce to 60 mg once daily, then permanently discontinue; from 180 mg once daily reduce to 120 mg once daily, then 90 mg once daily, then 60 mg once daily. Permanently discontinue if the patient cannot tolerate 60 mg once daily. ADVERSE-REACTION MODIFICATIONS (SPC Table 2) cover interstitial lung disease/pneumonitis (Grade 1 or 2 — withhold until recovery to baseline then resume at the same or next lower dose level, and do not escalate to 180 mg once daily if the event occurred in the first 7 days; recurrence or Grade 3 or 4 — permanently discontinue), hypertension, bradycardia, creatine phosphokinase elevation, lipase or amylase elevation, hepatotoxicity (permanently discontinue for Grade 2 or higher ALT or AST elevation above 3 x ULN with concurrent total bilirubin above 2 x ULN in the absence of cholestasis or haemolysis), hyperglycaemia, visual disturbance and other adverse reactions. ELDERLY: limited data suggest no dose adjustment is required in patients 65 years and older; no data above 85 years. HEPATIC: no adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) impairment; for severe impairment (Child-Pugh C) a reduced starting dose of 60 mg once daily for the first 7 days, then 120 mg once daily, is recommended. PAEDIATRIC: safety and efficacy in patients less than 18 years of age have not been established; no data are available.