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
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 indirect Coombs test may persist for up to 6 months after the last dose. Type and screen patient’s blood before initiating therapy if possible. 
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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