Ceritinib (Specialist drug)

Source: UK SPC (eMC) §4.2 for Zykadia 150 mg film-coated tablets (https://www.medicines.org.uk/emc/product/10128/smpc). VERBATIM: 'The recommended dose of Zykadia is 450 mg taken orally once daily with food at the same time each day. The maximum recommended dose with food is 450 mg taken orally once daily. Treatment should continue as long as clinical benefit is observed.' INITIATION: treatment should be initiated and supervised by a physician experienced in the use of anti-cancer medicinal products; ALK-positive NSCLC status must be established with an accurate and validated ALK assay before starting. MISSED DOSE / VOMITING: 'If a dose is missed, the patient should make up that dose, unless the next dose is due within 12 hours. If vomiting occurs during the course of treatment, the patient should not take an additional dose, but should continue with the next scheduled dose.' DOSE REDUCTION FOR ADVERSE REACTIONS: reduce in decrements of 150 mg daily (US label states the reduction sequence explicitly as first reduction 300 mg once daily with food, second reduction 150 mg once daily with food). 'Zykadia should be discontinued in patients unable to tolerate 150 mg daily taken with food.' Selected §4.2 Table 1 rules — withhold and restart 150 mg lower for severe/intolerable nausea, vomiting or diarrhoea despite optimal therapy; for ALT/AST > 5 x ULN with bilirubin ≤ 2 x ULN; for QTc > 500 msec on at least 2 ECGs (correct electrolytes, restart when QTc ≤ 480 msec or back to baseline); for persistent hyperglycaemia > 250 mg/dl despite optimal therapy; for grade ≥ 3 lipase or amylase elevation. PERMANENTLY DISCONTINUE for ALT/AST > 3 x ULN with bilirubin > 2 x ULN (absence of cholestasis or haemolysis), any grade treatment-related ILD/pneumonitis, QTc > 500 msec or > 60 msec change from baseline with torsade de pointes/polymorphic VT/serious arrhythmia, and life-threatening bradycardia where no contributing concomitant medicine is identified. STRONG CYP3A INHIBITORS: avoid; if unavoidable, reduce the dose by approximately one third (dose not clinically verified), rounded to the nearest multiple of the 150 mg dosage strength, with careful safety monitoring; resume the previous dose after the inhibitor is discontinued. HEPATIC IMPAIRMENT: in severe hepatic impairment reduce the dose by approximately one third, rounded to the nearest multiple of 150 mg; no adjustment in mild or moderate impairment. ELDERLY (≥ 65 years): limited data do not suggest a dose adjustment is required; no data above 85 years. PAEDIATRIC: 'The safety and efficacy of ceritinib in children and adolescents aged up to 18 years have not been established. No data are available.' — no paediatric dose is stated, so paedDose is null; verify any under-18 use against a children's formulary. MONITORING: liver tests (ALT, AST, total bilirubin) before starting, every 2 weeks for the first three months and monthly thereafter; periodic ECGs and electrolytes in at-risk patients; monitor for pulmonary symptoms of ILD/pneumonitis; fasting glucose. US cross-check (ZYKADIA, Novartis, label date 2025-12-15) gives the same 450 mg once daily with food.