SUMMARY  

• The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following schedule for the regimens listed below.¹
  • DARZALEX dosing schedule for monotherapy and in combination with lenalidomide or pomalidomide and low-dose dexamethasone ([Rd or Pd]; 4-week cycle)¹:
    • Weeks 1 to 8: weekly (total of 8 doses)
    • Weeks 9 to 24: every 2 weeks (total of 8 doses; first dose of the every-2-week dosing schedule is given at Week 9)
    • Week 25 onwards until disease progression: every 4 weeks (first dose of the every-4-week dosing schedule is given at Week 25)
  • DARZALEX dosing schedule with bortezomib, melphalan and prednisone ([VMP]; 6-week cycle)¹:
    • Weeks 1 to 6: weekly (total of 6 doses)
    • Weeks 7 to 54: every 3 weeks (total of 16 doses; first dose of the every-3-week dosing schedule is given at Week 7)
    • Week 55 onwards until disease progression: every 4 weeks (first dose of the every-4-week dosing schedule is given at Week 55)
  • DARZALEX dosing schedule for combination therapy with bortezomib, thalidomide and dexamethasone ([VTd]; 4-week cycle)¹:
    • Induction phase:
      • Weeks 1 to 8: weekly (total of 8 doses)
      • Weeks 9 to 16: every 2 weeks (total of 4 doses; first dose of the every-2-week dosing schedule is given at Week 9)
    • Stop for high dose chemotherapy and autologous stem cell transplant (ASCT)
    • Consolidation phase:
      • Weeks 1 to 8: every 2 weeks (total of 4 doses; first dose of the every-2-week dosing schedule is given at week 1 upon re-initiation of treatment following ASCT)
  • DARZALEX dosing schedule with bortezomib and dexamethasone ([Vd]; 3-week cycle dosing)¹:
    • Weeks 1 to 9: weekly (total of 9 doses)
    • Weeks 10 to 24: every 3 weeks (total of 5 doses; first dose of the every-3-week dosing schedule is given at Week 10)
    • Week 25 onwards until disease progression: every 4 weeks (first dose of the every-4-week dosing schedule is given at Week 25)
  • DARZALEX dosing schedule in combination with carfilzomib and dexamethasone ([Kd]; 4-week cycle)¹:
    • Week 1: 8 mg/kg on days 1 and 2 (total 2 doses)
    • Weeks 2 to 8: 16 mg/kg weekly (total of 7 doses)
    • Weeks 9 to 24: 16 mg/kg every 2 weeks (total of 8 doses; first dose of the every2week dosing schedule is given at Week 9)
    • Week 25 onwards until disease progression: 16 mg/kg every 4 weeks (first dose of the every4-week dosing schedule is given at Week 25)
• The recommended dose of 16 mg/kg to be administered on Day 1 when DARZALEX is administered as monotherapy or in combination may be split over two consecutive days, such that an  8 mg/kg on Day 1 and Day 2, respectively.¹ See full details in Table: Infusion Rates for DARZALEX (16 mg/kg) Administration.
• No dose reductions of DARZALEX are recommended. Consider withholding DARZALEX to allow recovery of blood cell counts in the event of myelosuppression, per Sections 5.3 and 5.4 of the DARZALEX Prescribing Information.¹
• For dosing instructions of combination agents administered with DARZALEX, see Section 14 Clinical Studies in the DARZALEX prescribing information and manufacturer's prescribing information for the combination agent.¹
• Following the dilution with 0.9% Sodium Chloride Injection, USP as outlined in Section 2.5 Preparation for Administration in the DARZALEX prescribing information, administer DARZALEX infusion intravenously at the appropriate infusion rate, as outlined in Table: Infusion Rates for DARZALEX (16 mg/kg) Administration. Consider incremental escalation of the infusion rate only in the absence of infusion-related reactions (IRRs).¹
  • For the week 2 infusion, use a dilution volume of 500 mL only if there were no IRRs the previous week. Otherwise, continue to use a dilution volume of 1000 mL.
  • Use a modified initial rate for subsequent infusions (i.e. week 3 onwards) only if there were no IRRs during the previous infusion. Otherwise, continue to use instructions for the week 2 infusion.
• For IRRs of any grade/severity, immediately interrupt the DARZALEX infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion, or treatment discontinuation of DARZALEX.¹

PRODUCT LABELING

Please note the following as stated in the DOSAGE AND ADMINISTRATION Section of the DARZALEX Prescribing Information:

2.1 Recommended Dose and Schedule

• Administer DARZALEX infusion intravenously at the appropriate infusion rate. Consider incremental escalation of the infusion rate only in the absence of IRRs. To facilitate administration, the recommended dose of 16 mg/kg to be administered on Day 1 when DARZALEX is administered as monotherapy or in combination may be split over two consecutive days, such that an 8 mg/kg on Day 1 and Day 2, respectively, as defined in Table: Infusion Rates for DARZALEX (16 mg/kg) Administration.¹
• No dose reductions of DARZALEX are recommended. Consider withholding DARZALEX to allow recovery of blood cell counts in the event of myelosuppression, per Sections 5.3 and 5.4 of the DARZALEX Prescribing Information.¹

• For IRRs of any grade/severity, immediately interrupt the DARZALEX infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion, or treatment discontinuation of DARZALEX as outlined¹:
  • Grade 1-2 (mild to moderate): Once reaction symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience any further reaction symptoms, infusion rate escalation may resume at increments and intervals as clinically appropriate up to the maximum rate of 200 mL/ hour (Table: Infusion Rates for DARZALEX (16 mg/kg) Administration).
  • Grade 3 (severe): Once reaction symptoms resolve, consider restarting the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, resume infusion rate escalation at increments and intervals as outlined in Table: Infusion Rates for DARZALEX (16 mg/kg) Administration. Repeat the procedure above in the event of recurrence of grade 3 symptoms. Permanently discontinue DARZALEX upon the third occurrence of a grade 3 or greater IRR.
  • Grade 4 (life threatening): Permanently discontinue DARZALEX.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 12 October 2023.