Lorlatinib (Specialist drug)

eMC SPC (Lorviqua 100 mg film coated tablets) §4.2: 'The recommended dose is 100 mg lorlatinib taken orally once daily.' Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products, and ALK-positive NSCLC must be confirmed by a proficient laboratory as these are the only patients for whom benefit has been shown. DURATION: continue as long as the patient is deriving clinical benefit without unacceptable toxicity. MISSED DOSE: take as soon as remembered unless it is less than 4 hours before the next dose, in which case skip it; do not take 2 doses at the same time. DOSE REDUCTIONS: first reduction 75 mg once daily; second reduction 50 mg once daily; permanently discontinue if the patient cannot tolerate 50 mg once daily. STRONG CYP3A4/5 INHIBITORS: if co-administration is unavoidable, reduce the starting dose from 100 mg to 75 mg once daily; on stopping the inhibitor, resume the previous dose after a washout of 3 to 5 half-lives of the inhibitor. TOXICITY MANAGEMENT (§4.2 Table 1): monitor serum cholesterol and triglycerides before starting, at 2, 4 and 8 weeks, then regularly — start or intensify lipid-lowering therapy for mild to severe hyperlipidaemia and continue lorlatinib at the same dose; for life-threatening hypercholesterolaemia (>12.92 mmol/L) or hypertriglyceridaemia (>11.4 mmol/L) withhold until recovery to moderate or mild, then re-challenge at the same dose while maximising lipid-lowering therapy, reducing by one dose level if it recurs. CNS effects (psychotic effects and changes in cognition, mood, mental state or speech): Grade 2-3 — withhold until Grade 1 or less then resume at one reduced dose level; Grade 4 — permanently discontinue. Lipase/amylase Grade 3-4: withhold until baseline then resume one dose level lower. ILD/pneumonitis Grade 1-2: withhold until baseline, consider corticosteroids, resume one dose level lower — permanently discontinue if it recurs or fails to recover after 6 weeks; Grade 3-4: permanently discontinue. AV block: monitor ECG before starting and monthly — see §4.2 Table 1 for the full first-degree/second-degree/complete AV block algorithm including pacemaker considerations. Grade 3 hypertension: withhold until Grade 1 or less (SBP <140 and DBP <90 mmHg) then resume at the same dose, reduced dose on recurrence, discontinue if control cannot be achieved. Grade 3-4 hyperglycaemia: withhold until controlled then resume at the next lower dose. HEPATIC IMPAIRMENT: no adjustment for mild or moderate; severe (Child-Pugh C) — reduce the starting dose from 100 mg to 50 mg once daily. ELDERLY (>=65 years): 'Due to the limited data on this population, no dose recommendation can be made for patients aged 65 years and older.' PAEDIATRIC: 'The safety and efficacy of lorlatinib in paediatric patients below 18 years have not been established. No data are available.' NOTE: eMC §4.4 and §4.8 were truncated at the source-fetch limit in the fetched bundle — clinician to verify against the full current SPC.