Crizotinib (Specialist drug)

INDICATION: adult patients with ALK-positive or ROS1-positive advanced non-small cell lung cancer. ALK or ROS1 status must be established with an accurate and validated assay before initiating therapy, and treatment must be initiated and supervised by a physician experienced in the use of anticancer medicinal products. MISSED DOSE: take as soon as remembered unless it is less than 6 hours until the next scheduled dose, in which case skip it; do not take two doses at the same time. ADULT DOSE REDUCTIONS: first reduction 200 mg twice daily; second reduction 250 mg once daily; permanently discontinue if unable to tolerate 250 mg once daily. ADULT TOXICITY MODIFICATIONS: Grade 3 haematological toxicity — withhold until recovery to Grade 2 or lower then resume at the same dose; Grade 4 — withhold then resume at the next lower dose (on recurrence resume at 250 mg once daily, and discontinue permanently on further Grade 4 recurrence). Grade 3 or 4 ALT/AST elevation with Grade 1 or lower bilirubin — withhold until Grade 1 or baseline, resume at 250 mg once daily and escalate to 200 mg twice daily if tolerated. Grade 2, 3 or 4 ALT/AST elevation with concurrent Grade 2, 3 or 4 bilirubin elevation (without cholestasis or haemolysis) — permanently discontinue. Any grade ILD/pneumonitis — withhold if suspected, permanently discontinue if treatment-related ILD/pneumonitis is diagnosed. Grade 3 QTc prolongation — withhold until Grade 1 or lower, correct electrolytes, resume at the next lower dose; Grade 4 — permanently discontinue. Grade 2-3 bradycardia — withhold until recovery to Grade 1 or heart rate 60 bpm or above and review contributing concomitant medicines; Grade 4 bradycardia — permanently discontinue if no contributing medicine is identified. Grade 4 visual loss — discontinue during evaluation. PAEDIATRIC REGIMEN (per body surface area, not per kg, so no structured paediatric field can be recorded): for paediatric patients with ALK-positive ALCL or ALK-positive IMT the recommended dosage is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity, given under adult supervision. BSA 1.34-1.51 m2 = 400 mg twice daily (800 mg/day); 1.52-1.69 m2 = 450 mg twice daily (900 mg/day); 1.70 m2 or more = 500 mg twice daily (1000 mg/day) using the 200 mg and 250 mg capsules. For BSA below 1.34 m2 the granules-in-capsules-for-opening formulation (20 mg, 50 mg, 150 mg) must be used: 0.38-0.46 m2 = 120 mg twice daily; 0.47-0.51 m2 = 140 mg; 0.52-0.61 m2 = 150 mg; 0.62-0.80 m2 = 200 mg; 0.81-0.97 m2 = 250 mg; 0.98-1.16 m2 = 300 mg; 1.17-1.33 m2 = 350 mg twice daily. No more than 4 capsules per single dose; the granules should not be sprinkled on food; dosing for BSA under 0.38 m2 has not been established. Efficacy and safety are established from 3 to under 18 years for ALCL and from 2 to under 18 years for IMT; there are no data below those ages, and safety and efficacy in paediatric NSCLC have not been established. HEPATIC IMPAIRMENT (adults): no starting-dose adjustment in mild impairment; moderate impairment (any AST and total bilirubin above 1.5 and up to 3 times ULN) start at 200 mg twice daily; severe impairment (any AST and total bilirubin above 3 times ULN) start at 250 mg once daily. For paediatric patients, moderate impairment starts at the first BSA-based dose reduction and severe impairment at the second. ELDERLY: no starting-dose adjustment required. MONITORING: liver function tests (ALT, AST, total bilirubin) weekly for the first 2 months then monthly; ECG and electrolytes before the first dose and periodically. Some sections of the product information we used were incomplete — check the full SPC.