Ixazomib (Specialist drug)

Source: UK SPC (eMC) 4.2 for Ixazomib 2.3 mg hard capsules (https://www.medicines.org.uk/emc/product/2378/smpc). VERBATIM: 'The recommended starting dose of ixazomib is 4 mg administered orally once a week on Days 1, 8, and 15 of a 28-day treatment cycle.' Treatment must be initiated and monitored under the supervision of a physician experienced in the management of multiple myeloma. COMBINATION BACKBONE (same 28-day cycle): lenalidomide 25 mg daily on Days 1 to 21; dexamethasone 40 mg on Days 1, 8, 15 and 22 - refer to the lenalidomide and dexamethasone SmPCs. BEFORE EACH NEW CYCLE: absolute neutrophil count should be >=1,000/mm3, platelets >=75,000/mm3, and non-haematological toxicities generally recovered to baseline or grade <=1. Continue until disease progression or unacceptable toxicity; treatment beyond 24 cycles should be based on an individual benefit-risk assessment as data beyond 24 cycles are limited. MISSED/VOMITED DOSE: take a delayed or missed dose only if the next scheduled dose is >=72 hours away; never take a missed dose within 72 hours of the next scheduled dose and never double up. If the patient vomits after a dose, do not repeat it - resume at the next scheduled dose. DOSE MODIFICATION: for overlapping toxicities of thrombocytopenia, neutropenia and rash, the first step is to withhold/reduce lenalidomide. Platelets <30,000/mm3 - withhold ixazomib and lenalidomide until platelets >=30,000/mm3, then resume lenalidomide at the next lower dose and ixazomib at its most recent dose; on recurrence, resume ixazomib at the next lower dose and lenalidomide at its most recent dose. ANC <500/mm3 - withhold both until ANC >=500/mm3 (consider G-CSF), then the same alternating reduction approach. Grade 2 or 3 rash - withhold lenalidomide until grade <=1, then resume lenalidomide lower; if it recurs, withhold both and resume ixazomib at the next lower dose; grade 4 rash - discontinue the regimen. Peripheral neuropathy: grade 1 with pain or grade 2 - withhold ixazomib until recovery to grade <=1 without pain or baseline, then resume at the most recent dose; grade 2 with pain or grade 3 - withhold, then resume at the next lower dose after recovery; grade 4 - discontinue the regimen. Other grade 3 or 4 non-haematological toxicity - withhold and, if attributable to ixazomib, resume at the next lower dose after recovery. CONCOMITANT MEDICATION: consider antiviral prophylaxis to reduce herpes zoster reactivation; thromboprophylaxis is recommended with the lenalidomide-dexamethasone combination, based on individual risk. ELDERLY: no dose adjustment required over 65 years. HEPATIC IMPAIRMENT: no adjustment in mild impairment; reduced starting dose of 3 mg in moderate (total bilirubin >1.5-3 x ULN) or severe (total bilirubin >3 x ULN) hepatic impairment. PAEDIATRIC: safety and efficacy in children below 18 years have not been established and no data are available, so paedDose is null; verify any under-18 use against a children's formulary and local protocol. NOTE: source SPC sections 4.4/4.8 were truncated at the fetch limit.