Daratumumab

Indication and product match: the pinned product is DARZALEX 20 mg/mL concentrate for solution for infusion (eMC product 7250), the intravenous weight-based formulation (not the subcutaneous formulation). Its §4.1 covers adult multiple myeloma: newly diagnosed transplant-ineligible (with lenalidomide + dexamethasone, or bortezomib + melphalan + prednisone), newly diagnosed transplant-eligible (with bortezomib + thalidomide + dexamethasone), after at least one prior therapy (with lenalidomide + dexamethasone, or bortezomib + dexamethasone), and as monotherapy in relapsed/refractory disease after a proteasome inhibitor and an immunomodulatory agent. No maximum dose is printed in the SPC. Infusion rates after dilution (Table 5): week 1 single-dose option 16 mg/kg in 1,000 mL starting at 50 mL/hour, increased by 50 mL/hour every hour to a maximum of 200 mL/hour; to facilitate administration the first 16 mg/kg dose may be split as 8 mg/kg on day 1 and 8 mg/kg on day 2, each in 500 mL; week 2 (16 mg/kg) in 500 mL at 50 mL/hour, but only if there were no infusion-related reactions (IRRs) the previous week, otherwise use 1,000 mL; week 3 onwards in 500 mL starting at 100 mL/hour only if there were no IRRs during the previous infusion, otherwise use the week 2 instructions; maximum rate 200 mL/hour. Escalate the rate only in the absence of IRRs. Pre-infusion medicines 1-3 hours before every infusion: a long- or intermediate-acting corticosteroid (monotherapy: methylprednisolone 100 mg IV, which may be reduced to 60 mg orally or IV after the second infusion; combination therapy: dexamethasone 20 mg or equivalent), an antipyretic (oral paracetamol 650 to 1,000 mg) and an antihistamine (oral or IV diphenhydramine 25 to 50 mg or equivalent). Post-infusion: monotherapy - oral corticosteroid (methylprednisolone 20 mg or equivalent) on each of the two days after all infusions; combination therapy - consider low-dose oral methylprednisolone 20 mg or less the day after (may not be needed if a background regimen corticosteroid is given that day). Consider bronchodilators and inhaled corticosteroids after infusion in patients with a history of COPD, and anti-viral prophylaxis against herpes zoster reactivation. Background regimen doses quoted in the SPC: with lenalidomide + dexamethasone dexamethasone 40 mg/week (20 mg/week if over 75 years); with bortezomib + dexamethasone, dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib cycles (or 20 mg/week if over 75 years, underweight with BMI below 18.5, poorly controlled diabetes or prior steroid intolerance); for other combination partners follow their own SPCs. IRR management: interrupt the infusion for any IRR; grade 1-2 - resume at no more than half the rate at which the reaction occurred; grade 3 - restart may be considered at no more than half that rate, and discontinue permanently on the third occurrence of a grade 3 or greater IRR; grade 4 - discontinue permanently. Missed dose: give as soon as possible and adjust the schedule, maintaining the treatment interval. No dose reductions are recommended; delay may be needed to allow recovery of blood counts. No dose adjustment in the elderly. Paediatric: DARZALEX is not recommended in children below 18 years of age as efficacy has not been established.