Isatuximab (Specialist drug)

Source: UK SPC (eMC) 4.2 for Sarclisa 1400 mg solution for injection (https://www.medicines.org.uk/emc/product/102350/smpc). VERBATIM: 'The recommended dose of isatuximab subcutaneous is 1400 mg administered as subcutaneous injection with CirCLIQ On-Body Delivery System (OBDS) or with a syringe and infusion set for manual administration.' THIS SPC COVERS THE SUBCUTANEOUS 1400 mg FORMULATION ONLY - it does not give the posology of the intravenous formulation (section 4.8 refers to an intravenous isatuximab 10 mg/kg regimen but no IV posology is stated in section 4.2); source the IV SPC separately if the intravenous regimen is needed. Must be prescribed by a specialist in the treatment of malignancies and administered by a healthcare professional; for the first dose only, immediate access to medical support must be available. After cycle 1, subsequent injections may be given at the patient's home by a healthcare professional if there was no systemic administration reaction in the previous cycle. ALTERNATIVE SCHEDULES with bortezomib, lenalidomide and dexamethasone: newly diagnosed multiple myeloma ineligible for autologous stem cell transplant - Cycle 1 (42-day cycle) 1400 mg on days 1, 8, 15, 22 and 29; cycles 2 to 4 (42-day cycles) every 2 weeks on days 1, 15 and 29; cycles 5 to 17 (28-day cycles) every 2 weeks on days 1 and 15; cycles 18 and beyond (28-day cycles) every 4 weeks on day 1. Newly diagnosed multiple myeloma eligible for ASCT (induction) - Cycle 1 (42-day cycle) 1400 mg on days 1, 8, 15, 22 and 29; cycles 2 to 3 (42-day cycles) every 2 weeks on days 1, 15 and 29, then stop for intensification (high-dose chemotherapy and ASCT) followed by standard-of-care maintenance. Patients on intravenous isatuximab may switch to subcutaneous at any time once cycle 1 is completed. PREMEDICATION 15-60 minutes before each administration: dexamethasone 40 mg (20 mg for patients aged 75 years or over) when combined with pomalidomide, or dexamethasone 20 mg when combined with carfilzomib or with bortezomib and lenalidomide (this dexamethasone dose is the total dose given once, serving as both premedication and backbone treatment); montelukast 10 mg orally (or equivalent) at cycle 1 only; paracetamol/acetaminophen 650-1000 mg orally (or equivalent); diphenhydramine 25-50 mg intravenously or orally (or equivalent) - the intravenous route is preferred for at least the first 4 administrations. Premedication need may be reconsidered in patients with no systemic administration reaction after the first 4 administrations. DOSE ADJUSTMENT: dose reduction is NOT permitted; dose delay or omission may be required. Grade 2 or 3 systemic administration reaction - stop the current administration, give diphenhydramine 25 mg IV and/or methylprednisolone 100 mg IV (or equivalent) and supportive care; for grade 3 consider resuming at the next planned administration; permanently discontinue on a third grade 3 occurrence or any grade 4. Grade 2 injection site reaction - interrupt and resume after recovery to grade <=1 with pauses or slower administration; grade 3 or 4 - permanently discontinue. Missed dose: give as soon as possible and adjust the schedule, maintaining the treatment interval. NEUTROPENIA: dose delay/omission and colony-stimulating factors (e.g. G-CSF) per local guidelines. INFECTION: consider antibacterial and antiviral (e.g. herpes zoster) prophylaxis. ELDERLY: no dose adjustment. HEPATIC IMPAIRMENT: no dose adjustment in mild impairment; limited/no data in moderate/severe but no evidence that adjustment is required. PAEDIATRIC: safety and effectiveness in children below 18 years have not been established and no subcutaneous 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.