Alectinib [Specialist drug]

Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. A validated ALK assay is necessary to select ALK-positive NSCLC patients, and ALK-positive status should be established before starting therapy. MISSED OR DELAYED DOSES: a missed dose can be made up unless the next dose is due within 6 hours; two doses must not be taken at the same time to make up for a missed dose. If vomiting occurs after a dose, the next dose should be taken at the scheduled time. DOSE ADJUSTMENT FOR ADVERSE REACTIONS (SPC Table 2): ILD/pneumonitis of any severity grade — immediately interrupt, and permanently discontinue if no other potential cause is identified. ALT or AST above 5 times the upper limit of normal with total bilirubin at or below 2 times ULN — temporarily withhold until recovery to baseline or to 3 times ULN or below, then resume at a reduced dose. ALT or AST above 3 times ULN with total bilirubin above 2 times ULN in the absence of cholestasis or haemolysis — permanently discontinue. Bradycardia (heart rate below 60 bpm) grade 2 or 3 — temporarily withhold until recovery to grade 1 or below or a heart rate of at least 60 bpm, evaluate concomitant medicines known to cause bradycardia and antihypertensives; if a contributing medicine is identified and stopped or dose-adjusted, resume at the previous dose on recovery, otherwise resume at a reduced dose on recovery. Bradycardia grade 4 — permanently discontinue if no contributing concomitant medicine is identified; if one is identified and stopped or adjusted, resume at a reduced dose on recovery with frequent monitoring, and permanently discontinue on recurrence. CPK above 5 times ULN — temporarily withhold until recovery to baseline or to 2.5 times ULN or below, then resume at the same dose. CPK above 10 times ULN, or a second occurrence above 5 times ULN — withhold until recovery to baseline or 2.5 times ULN or below, then resume at a reduced dose. Haemolytic anaemia with haemoglobin below 10 g/dL (grade 2 or above) — withhold until resolution, then resume at a reduced dose. Severe hypertriglyceridaemia (triglycerides 501 to 1,000 mg/dL, or 5.71 to 11.4 mmol/L) or life-threatening hypertriglyceridaemia (above 1,000 mg/dL or above 11.4 mmol/L) — withhold until recovery to at least moderate hypertriglyceridaemia (triglycerides at or below 500 mg/dL or 5.7 mmol/L), evaluate and address treatable risk factors for pancreatitis before resuming, and if an acute episode of pancreatitis occurs withhold until full recovery; treatment may then be resumed at the same dose with regular triglyceride monitoring. ELDERLY: the limited data in patients aged 65 and over do not suggest that a dose adjustment is required; there are no available data in patients over 80 years of age. EXTREME BODY WEIGHT: pharmacokinetic simulations do not indicate low exposure above 130 kg, but clinical studies enrolled patients in the range 36.9 to 123 kg and there are no data above 130 kg. PAEDIATRIC: safety and efficacy in children and adolescents below 18 years of age have not been established and no data are available, so no paediatric dose exists to publish. TRUNCATION: §4.4 and §4.8 were both cut at the source-fetch limit, so the warnings and adverse-reaction material recorded here is partial and must be completed from the SPC itself; §4.2 was retrieved complete, so the posology above is not affected.