Lenvatinib (Specialist drug)

eMC SPC (Lenvatinib Eisai 10 mg hard capsules) §4.2. Treatment should be initiated and supervised by a healthcare professional experienced in the use of anticancer therapies. INDICATION-SPECIFIC DOSES (all oral, once daily): (1) Differentiated thyroid cancer — 24 mg once daily; dose reductions 20 mg, then 14 mg, then 10 mg once daily. (2) Hepatocellular carcinoma — 8 mg (two 4-mg capsules) once daily if body weight <60 kg, or 12 mg (three 4-mg capsules) once daily if body weight >=60 kg; dose adjustments are based only on observed toxicity, not on body-weight changes during treatment; reductions in succession 12 mg / 8 mg / 4 mg / 4 mg every other day. (3) Endometrial carcinoma — 20 mg once daily in combination with pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks by intravenous infusion over 30 minutes; lenvatinib reductions 14 mg, then 10 mg, then 8 mg once daily. (4) Renal cell carcinoma, first line — 20 mg once daily with pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks IV over 30 minutes; reductions 14 mg, 10 mg, 8 mg. (5) Renal cell carcinoma, second line — 18 mg once daily (one 10-mg plus two 4-mg capsules) in combination with everolimus 5 mg once daily; reductions 14 mg, 10 mg, 8 mg. Limited data are available for doses below 8 mg (below 10 mg in DTC). MISSED DOSE: if a dose cannot be taken within 12 hours it should be skipped and the next dose taken at the usual time. TOXICITY MANAGEMENT: optimal medical management of nausea, vomiting and diarrhoea should be started before any interruption or dose reduction, and gastrointestinal toxicity actively treated to reduce the risk of renal impairment or failure. Grade 1-2 reactions generally do not warrant interruption unless intolerable; Grade 3 or intolerable reactions require interruption until Grade 0-1 or baseline, then resumption at a reduced dose; discontinue for life-threatening (Grade 4) reactions except non-life-threatening laboratory abnormalities, which are managed as Grade 3. Discontinue and do not resume for arterial thromboembolism (any grade), nephrotic syndrome, Grade 4 hypertension, Grade 4 renal impairment/failure, Grade 4 cardiac dysfunction, Grade 4 hepatotoxicity, Grade 4 haemorrhage, Grade 4 GI perforation/fistula, Grade 4 non-GI fistula, and Grade 4 diarrhoea despite medical management; interrupt for proteinuria >=2 g/24 hours (resume when <2 g/24 hours) and for QT interval >500 ms (resume when <480 ms or baseline). HYPERTENSION: blood pressure must be well controlled before starting (stable antihypertensive dose for at least 1 week if known hypertensive) and monitored after 1 week of treatment, then every 2 weeks for the first 2 months and monthly thereafter (§4.4 Table 6). HEPATIC IMPAIRMENT: DTC — no starting-dose change for Child-Pugh A or B, 14 mg once daily in Child-Pugh C; EC and RCC — no change for Child-Pugh A or B, 10 mg once daily in Child-Pugh C; HCC — no change in Child-Pugh A, insufficient data for Child-Pugh B (close safety monitoring), not recommended in Child-Pugh C. ELDERLY: no starting-dose adjustment on the basis of age; limited data above 75 years. PAEDIATRIC: 'The safety and efficacy of lenvatinib in children aged 2 to <18 years have not been established... no recommendation on a posology can be made. Lenvatinib should not be used in children younger than 2 years of age because of safety concerns identified in animal studies.' 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.