Lenalidomide

Source: UK SPC (eMC) for Lenalidomide 10 mg capsules, §4.2 (https://www.medicines.org.uk/emc/product/14289/smpc). Treatment should be supervised by a physician experienced in the use of anti-cancer therapies. Dose is modified based upon clinical and laboratory findings; dose adjustments during treatment and on restart are recommended to manage Grade 3 or 4 thrombocytopenia, neutropenia or other Grade 3 or 4 toxicity judged related to lenalidomide. MISSED DOSE: if less than 12 hours has elapsed the patient can take the dose; if more than 12 hours has elapsed, skip it and take the next dose at the normal time the following day. OTHER REGIMENS STATED IN §4.2 — (1) NDMM, transplant-ineligible, with dexamethasone (the regimen above): must not be started if ANC < 1.0 x 10^9/L and/or platelets < 50 x 10^9/L; dexamethasone 40 mg orally once daily on days 1, 8, 15 and 22 of each 28-day cycle; lenalidomide dose reduction steps 25 mg > 20 mg > 15 mg > 10 mg > 5 mg > 2.5 mg. (2) NDMM, transplant-ineligible, with bortezomib and dexamethasone: lenalidomide 25 mg orally once daily days 1-14 of each 21-day cycle, with bortezomib 1.3 mg/m2 body surface area subcutaneously twice weekly on days 1, 4, 8 and 11 of each 21-day cycle, for up to eight 21-day cycles (24 weeks); then continued treatment with lenalidomide 25 mg orally once daily days 1-21 of repeated 28-day cycles plus dexamethasone until progression. (3) NDMM, transplant-ineligible, with melphalan and prednisone: lenalidomide 10 mg orally once daily days 1 to 21 of repeated 28-day cycles for up to 9 cycles, melphalan 0.18 mg/kg orally days 1 to 4 and prednisone 2 mg/kg orally days 1 to 4 of repeated 28-day cycles; thereafter lenalidomide monotherapy 10 mg orally once daily days 1 to 21 of repeated 28-day cycles until progression; must not be started if ANC < 1.5 x 10^9/L and/or platelets < 75 x 10^9/L. (4) Maintenance after autologous stem cell transplantation (ASCT): 10 mg orally once daily continuously (days 1 to 28 of repeated 28-day cycles) until progression or intolerance; after 3 cycles the dose can be increased to 15 mg orally once daily if tolerated; do not dose below 5 mg (days 1-21 every 28 days); must not be started if ANC < 1.0 x 10^9/L and/or platelets < 75 x 10^9/L. (5) Multiple myeloma with at least one prior therapy: 25 mg orally once daily days 1 to 21 of repeated 28-day cycles, with dexamethasone 40 mg orally once daily on days 1-4, 9-12 and 17-20 of each 28-day cycle for the first 4 cycles, then 40 mg once daily on days 1-4 every 28 days; dose reduction steps 25 mg > 15 mg > 10 mg > 5 mg, do not dose below 5 mg once daily. (6) Follicular lymphoma: 20 mg orally once daily on days 1 to 21 of repeated 28-day cycles for up to 12 cycles, with rituximab 375 mg/m2 intravenously weekly in cycle 1 (days 1, 8, 15, 22) and day 1 of every 28-day cycle for cycles 2 to 5; dose levels -1 15 mg, -2 10 mg, -3 5 mg (days 1-21 every 28 days); all patients should receive tumour lysis syndrome prophylaxis (allopurinol, rasburicase or equivalent) and be well hydrated orally during the first week of the first cycle. ALL INDICATIONS: for other Grade 3 or 4 toxicities related to lenalidomide, stop treatment and restart only at the next lower dose level when toxicity has resolved to <= Grade 2; consider interruption or discontinuation for Grade 2 or 3 skin rash; must be discontinued permanently for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or bullous rash, or if SJS, TEN or DRESS is suspected. ELDERLY: because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and renal function should be monitored; patients with NDMM aged 75 years and older should be carefully assessed before treatment, and for those older than 75 treated with lenalidomide plus dexamethasone the starting dose of dexamethasone is 20 mg once daily on days 1, 8, 15 and 22 of each 28-day cycle. PAEDIATRIC (non-numeric, so no structured paedDose): 'Lenalidomide should not be used in children and adolescents from birth to less than 18 years because of safety concerns.' COVERAGE GAP — the fetched §4.2 is TRUNCATED partway through the renal impairment paragraph, so it does NOT contain the myelodysplastic syndromes (MDS with del(5q)) or mantle cell lymphoma regimens, nor the full renal dose table. The US label section in this bundle summarises 'MDS: 10 mg once daily' and 'MCL: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles' and states 'Renal impairment: Adjust starting dose based on the creatinine clearance value' — these US figures are NOT from the UK SPC and must be verified against the full UK SPC before use. No absolute maximum daily dose is stated in the fetched §4.2 (25 mg once daily is the highest starting dose stated).