Parenteral Manual

Daratumumab (NON-FORMULARY)

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Alternate Name(s): 
Darzalex®, HuMax-CD38
Classification: 
Antineoplastic, anti-CD38 monoclonal antibody; NON-CYTOTOXIC HAZARDOUS
Original Date: 
February 2022
Revised Date: 
April 2026
Indications: 
  • Treatment of adults with either newly diagnosed or relapsed/refractory multiple myeloma, in combination with other chemotherapies.
  • Investigational use for children and young adults (up to 30 years old) with relapsed or refractory precursor T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma.
Reconstitution and Stability: 
  • Supplied as a colourless to yellow concentrated solution in a single-use glass vial containing either 400 mg/20 mL or 100 mg/5 mL.
  • Store vials in refrigerator (2-8 C).  Do not freeze. Protect from light.  Do not shake.
  • Dilution: Daratumumab concentrated solution should be further diluted in 0.9% Sodium Chloride Injection (Normal Saline) prior to IV infusion.
  • Make an exact volume 0.9% Sodium chloride IV bag in an empty PVC or polyolefin bag.  Add the dose of daratumumab. Gently invert the bag to the mix the solution, DO NOT SHAKE.
  • Diluted solution can be stored up to 15 hours at room temperature (including administration time) or up to 24 hours (total) with refrigeration. Protect from light.
  • If the infusion exceeds 15 hours, the daratumumab bag must be changed.
Compatibility: 
  • Solutions Compatible:  0.9% NaCl
  • Additives/Above Cassette Compatible: Do not mix with other drugs or IV solutions
  • Y-site Compatible: Do not run with other drugs
Administration: 

(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

SC NO
IM

NO
IV Direct NO
IV Intermittent Infusion

YES

 

  • For first infusion: Dilute dose in 0.9% NaCl to a final volume of 500 mL. Administer at an initial rate of 20 mL/hr. In the absence of infusion-related reactions/hypersensitivity, the rate of the infusion will be escalated in increments of 20 mL/hr every 60 minutes for the first 3 hours, to a maximum rate of 80 mL/hr.
  • For second and subsequent infusions: Dilute dose in 0.9% NaCl to a final volume of 250 mL ONLY IF no infusion reaction occurred during the first 3 hours of the first infusion (otherwise, follow the instructions for the first infusion). Administer at an initial rate of 20 mL/hr and increase by 20 mL/hr at 60 minute intervals, as tolerated, to a maximum rate of 80 mL/hr.

  • "Administer the diluted solution using an infusion set with an in-line 0.2 μm filter
IV Continuous Infusion NO

 

Dosage: 

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

Pediatric (Investigational):

  • Premedication with methylprednisolone, cetrizine, acetaminophen and montelukast recommended 1 hour before the start of each infusion.  
  • Daratumumab Dose:  16 mg/kg
    • Cycles 1 and 2: Days 1, 8, 15 and 22 (weekly)
    • Cycles 3, 4, 5, and 6: Days 1 and 15 (q 2 Weeks)
    • Cycle 7 and greater: Day 1 (monthly)
  • All cycles are 28-day cycles. The first visit of a cycle should be 4 weeks after the start of the previous cycle.
  • Post-medication with oral prednisone is recommended for the prevention of delayed infusion-reactions, for the two days following the infusions.
  • For patients with a higher risk of respiratory complications, post-treatment with antihistamines for 2 days, short-acting β2 adrenergic receptor agonists and/or control medications for lung disease may be considered.
Potential hazards of parenteral administration: 

Common/Occasional:

  • Infusion-related reactions are reported in nearly 50% of patients (adult data) during the first infusion, and in 2-4% of patients during subsequent infusions. Reactions generally occur during infusion or within 4 hours of completion of the infusion.
  • Infusion interruption is indicated for reactions of any grade/severity and prompt symptom management should occur (e.g., corticosteroids, epinephrine, bronchodilators, oxygen).
  • Depending on the reaction and its severity, restarting the infusion at a reduced rate (no more than half the rate at which the reaction occurred) could be considered, at the physician’s discretion.
  • In the event of a life-threatening infusion-related reaction, daratumumab should be discontinued and no further daratumumab should be administered.
  • GI: constipation, decreased appetite, diarrhea, nausea, vomiting.
  • CNS: fatigue, headache
  • Cardiovascular: hypertension
  • Hematologic: anemia, thrombocytopenia, neutropenia, lymphocytopenia
  • Respiratory: cough, dyspnea, nasal congestion, nasopharyngitis, pneumonia, upper respiratory tract infection.
  • Neuromuscular: arthralgia, back pain, limb pain, musculoskeletal chest pain
  • Misc: fever

Rare:

  • Hepatitis B virus (HBV) reactivation, in some cases fatal, has been reported in patients treated with daratumumab. HBV screening should be performed in all patients before initiation of daratumumab.
Notes: 
  • Considered low emetogenic potential.
  • Daratumumab may interfere with cross-matching and red blood cell antibody screening; interference with may persist for up to 6 months after the last dose. Order a RBC phenotype/genotype before initiating therapy if possible. This will allow the administration of phenotypically matched blood and prevent formation of allo-antibodies during Daratumumab therapy. Turn around time is expected to be prolonged in order to be able to issue phenotypically matched RBC transfusions for patients that have received Daratumumab in the last 6 months
     
References: 
  1. Daratumumab Product Monograph. Janssen Inc Canada, Version: 8 December 2021.
  2. Daratumumab Pediatric Infusion Recommendations. Janssen Inc and R. Carson. 01 August 2016.
  3. Daratumumab Drug Monograph. Cancer Care Ontario. January 2022.

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