Bortezomib

SCOPE: multiple myeloma (and mantle cell lymphoma) - the indications dosed in the fetched labels, and the page's primary indication. ROUTE CAVEAT: the fetched UK SPC is the 1 mg vial, which is INTRAVENOUS ONLY - verbatim section 4.4: 'Bortezomib 1 mg powder for solution for injection is for intravenous use only, while bortezomib 2.5 mg and 3.5 mg powder for solution for injection are for intravenous or subcutaneous use.' The subcutaneous route (which the page presents as preferred) is sourced here only from the US label, verbatim: 'The recommended starting dose of bortezomib for injection is 1.3 mg/m2 administered either as a 3 to 5 second bolus intravenous injection or subcutaneous injection' and 'Bortezomib for injection is administered intravenously at a concentration of 1 mg/mL, or subcutaneously at a concentration of 2.5 mg/mL'. The 1.3 mg/m2 figure is the same for both routes. NO maxDose IS PUBLISHED: neither label uses maximum-dose wording anywhere; 1.3 mg/m2 is described as 'the recommended dose'/'the recommended starting dose', and every modification in both labels moves the dose DOWN (1.3 -> 1.0 -> 0.7 mg/m2). || REGIMENS, verbatim UK SPC 4.2. Relapsed myeloma monotherapy: '1.3 mg/m2 body surface area twice weekly for two weeks on days 1, 4, 8, and 11, in a 21-day treatment cycle... At least 72 hours should elapse between consecutive doses of bortezomib.' 'It is recommended that patients receive 2 cycles of bortezomib following a confirmation of a complete response. It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles.' With pegylated liposomal doxorubicin: bortezomib 1.3 mg/m2 on days 1, 4, 8, 11 of a 21-day cycle, with 'Pegylated liposomal doxorubicin... administered at 30 mg/m2 on day 4 of the bortezomib treatment cycle as a 1 hour intravenous infusion administered after the bortezomib injection', up to 8 cycles. With dexamethasone (relapsed): bortezomib 1.3 mg/m2 days 1, 4, 8, 11 of a 21-day cycle with 'Dexamethasone... administered orally at 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the bortezomib treatment cycle.' Previously untreated myeloma, transplant-INELIGIBLE, with melphalan and prednisone (9 six-week cycles): 'In Cycles 1-4, bortezomib is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32. In Cycles 5-9, bortezomib is administered once weekly on days 1, 8, 22 and 29', with melphalan 9 mg/m2 and prednisone 60 mg/m2 orally on days 1-4 of the first week of each cycle. Previously untreated myeloma, transplant-ELIGIBLE induction with dexamethasone: bortezomib 1.3 mg/m2 days 1, 4, 8, 11 of a 21-day cycle with 'Dexamethasone... administered orally at 40 mg on days 1, 2, 3, 4, 8, 9, 10 and 11', four cycles. With dexamethasone and thalidomide: bortezomib 1.3 mg/m2 days 1, 4, 8, 11 of a 28-day cycle, dexamethasone 40 mg orally on days 1-4 and 8-11, 'Thalidomide is administered orally at 50 mg daily on days 1-14 and if tolerated the dose is increased to 100 mg on days 15-28, and thereafter may be further increased to 200 mg daily from cycle 2', four cycles (two more for at least partial response). Previously untreated mantle cell lymphoma (BR-CAP): bortezomib 1.3 mg/m2 'twice weekly for two weeks on days 1, 4, 8, and 11, followed by a 10-day rest period on days 12-21', six cycles, with rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 intravenously on day 1 and prednisone 100 mg/m2 orally on days 1-5 of each cycle. || DOSE REDUCTION FOR TOXICITY, verbatim: 'Bortezomib treatment must be withheld at the onset of any Grade 3 non-haematological or any Grade 4 haematological toxicities, excluding neuropathy... Once the symptoms of the toxicity have resolved, bortezomib treatment may be re-initiated at a 25% reduced dose (1.3 mg/m2 reduced to 1.0 mg/m2; 1.0 mg/m2 reduced to 0.7 mg/m2).' NEUROPATHY (SPC Table 1): Grade 1 with no pain or loss of function - no change; Grade 1 with pain or Grade 2 - 'Reduce bortezomib to 1.0 mg/m2 or Change bortezomib treatment schedule to 1.3 mg/m2 once per week'; Grade 2 with pain or Grade 3 - withhold until resolved then 're-initiate Bortezomib treatment and reduce dose to 0.7 mg/m2 once per week'; Grade 4 and/or severe autonomic neuropathy - 'Discontinue bortezomib'. || ADMINISTRATION, verbatim: 'The reconstituted solution is administered as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter followed by a flush with sodium chloride 9 mg/ml (0.9%) solution for injection.' FATAL ROUTE ERROR, verbatim SPC 4.4: 'There have been fatal cases of inadvertent intrathecal administration of bortezomib... Bortezomib should not be administered intrathecally.' || PAEDIATRIC, verbatim SPC 4.2: 'The safety and efficacy of bortezomib in children below 18 years of age have not been established... no recommendation on a posology can be made.' US label 8.4: 'Safety and effectiveness have not been established in pediatric patients.' || ELDERLY, verbatim SPC: 'There is no evidence to suggest that dose adjustments are necessary in patients over 65 years of age with multiple myeloma or with mantle cell lymphoma.' || Sections 4.4 and 4.8 of the SPC and sections 5 and 6 of the US label were truncated at the source-fetch limit. || PRIOR HOLD ANSWERED: this record was previously held on ROUTE - it narrowed the page to IV only from the IV-only 1 mg vial while the page presents SC as preferred. The subcutaneous route is now sourced, from the openFDA record in this same bundle, and both routes are stated with their presentations. The prior verify confirmed every number here traces verbatim to the SPC.