DARZALEX

Antineoplastic Monoclonal Antibodies Targeting CD38

Emetic Risk
Minimal

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
The daratumumab solution in single-dose vials is colorless to pale yellow. It is a protein and the diluted solution may develop very small, translucent to white particles; do not use diluted solutions containing visibly opaque particles, discoloration, or foreign particles.[60311]

Daratumumab is available as a 20 mg/mL solution in 100 mg/5 mL and 400 mg/20 mL vials; each of these vial strengths has 2 National Drug Codes (NDCs).
Dilute prior to administration; vials of the same strength with different NDCs may be admixed in the same infusion bag.
Premedication with acetaminophen PO, diphenhydramine IV or PO, and a corticosteroid is required prior to each infusion; hold therapy for infusion-related reactions.
If a dose is missed, administer daratumumab as soon as possible and adjust the dosing schedule to maintain the treatment interval.
Initial dilution volume and/or infusion rate differ for first, second, and subsequent infusions; the maximum infusion rate is 200 mL/hour.
Dilution:
Withdraw the appropriate amount (mL) from the daratumumab 20 mg/mL vials for the calculated dose (use actual body weight); discard any unused portion left in the vial.
For the first infusion (week 1), dilute the calculated amount in 0.9% sodium chloride injection to a total infusion bag volume of 1,000 mL for a single-dose infusion (16 mg/kg) or 500 mL for split-dose infusions (8 mg/kg). For subsequent infusions, dilute the calculated amount in 0.9% sodium chloride injection to a total infusion bag volume of 500 mL. Following a single-dose infusion (16 mg/kg), reduce the total infusion bag volume to 500 mL only if there were no grade 1 or higher infusion reactions during the previous week.
Gently invert the bag to mix the solution but do not shake.
Infusion bags/containers must be made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE) or polyolefin blend.
Storage of admixture: store at room temperature (15 to 25 degrees C or 59 to 77 degrees F) for up to 15 hours (includes infusion time) or for up to 24 hours refrigerated (2 to 8 degrees C or 36 to 46 degrees F) and protected from light; allow refrigerated admixtures to warm to room temperature prior to use.
Intravenous Infusion:
Administer daratumumab using an infusion-set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone filter (pore size of 0.2 or 0.22 micrometer); polyurethane, polybutadiene (PBD), PVC, PP, or PE administration sets must be used.
Do not infuse other drugs concomitantly in the same IV line.
Administer the diluted infusion intravenously at the appropriate infusion rate as follows: Week 1 infusion(s): start at 50 mL/hour, increase by 50 mL/hour every hour to a maximum rate of 200 mL/hour.Week 2 infusion (following a single 16 mg/kg dose infusion only): start at 50 mL/hour, increase by 50 mL/hour every hour to a maximum rate of 200 mL/hour.Subsequent infusions: start at 100 mL/hour, increase by 50 mL/hour every hour to a maximum rate of 200 mL/hour if there were no grade 1 or higher infusion reactions during the previous week.
Do not save or store unused daratumumab for reuse.[60311]

neutropenia / Delayed / 15.0-82.0
lymphopenia / Delayed / 25.0-71.0
thrombocytopenia / Delayed / 9.0-47.0
infection / Delayed / 0-37.0
leukopenia / Delayed / 0-35.0
anemia / Delayed / 4.0-30.0
hypertension / Early / 4.0-20.0
fatigue / Early / 2.0-18.0
pulmonary edema / Early / 0-15.0
atrial fibrillation / Early / 0-15.0
pancreatitis / Delayed / 0-15.0
leukoencephalopathy / Delayed / 0-15.0
infusion-related reactions / Rapid / 2.0-12.0
diarrhea / Early / 1.0-7.0
dyspnea / Early / 0-7.0
hyperglycemia / Delayed / 0-7.0
back pain / Delayed / 0-6.0
peripheral neuropathy / Delayed / 0-5.0
insomnia / Early / 0-4.7
skin cancer / Delayed / 0-4.7
nausea / Early / 0-4.0
bone pain / Delayed / 0-4.0
edema / Delayed / 1.0-4.0
peripheral edema / Delayed / 1.0-4.0
influenza / Delayed / 0-3.5
hypercalcemia / Delayed / 0-3.5
fever / Early / 1.0-3.0
tremor / Early / 0-3.0
hypokalemia / Delayed / 0-3.0
vomiting / Early / 0-2.0
musculoskeletal pain / Early / 0-2.0
arthralgia / Delayed / 0-2.0
dizziness / Early / 0-2.0
headache / Early / 0-1.2
constipation / Delayed / 0-1.0
anorexia / Delayed / 0-1.0
muscle cramps / Delayed / 0-1.0
cough / Delayed / 0-1.0
hypocalcemia / Delayed / 0-1.0
hepatitis B exacerbation / Delayed / 0-1.0
laryngeal edema / Rapid / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
new primary malignancy / Delayed / Incidence not known

chest pain (unspecified) / Early / 0-15.0
dehydration / Delayed / 0-15.0
antibody formation / Delayed / 0.3-0.3
hypoxia / Early / Incidence not known
blurred vision / Early / Incidence not known
hypotension / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
myopia / Delayed / Incidence not known

asthenia / Delayed / 0-28.0
chills / Rapid / 0-20.0
nasal congestion / Early / 0-17.0
paresthesias / Delayed / 0-16.0
pruritus / Rapid / 0-15.0
rash / Early / 0-15.0
anxiety / Delayed / 0-13.0
ocular pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
myalgia / Early / Incidence not known
throat irritation / Early / Incidence not known
syncope / Early / Incidence not known

DARZALEX

Rx

Anti-CD38 monoclonal antibody
Used as monotherapy or in combination with other agents for multiple myeloma
Type and cross-match patient blood prior to starting treatment

No dosage adjustments are necessary for patients with pre-existing mild (total bilirubin level of 1 to 1.5-times the upper limit of normal (ULN) and any ALT level) or moderate (total bilirubin level 1.5 to 3-times the ULN and any ALT level) hepatic impairment based on a population pharmacokinetic analysis. Daratumumab has not been evaluated in patients with severe hepatic impairment (total bilirubin level greater than 3-times the ULN and any ALT level).

No daratumumab dosage adjustment is necessary for patients with pre-existing renal impairment based on a population pharmacokinetic analysis.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

16 mg/kg/dose (actual body weight) IV.

16 mg/kg/dose (actual body weight) IV.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Daratumumab is a human monoclonal antibody that binds to CD38 IgG1 (kappa subclass), a type II transmembrane glycoprotein, resulting in apotosis via Fc-mediated cross linking, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis. CD38 is expressed on myeloid-derived suppressor cells and some regulatory T-cells (CD38+Tregs ); these cells are sensitive to daratumumab.

Daratumumab is administered as an IV infusion. In a population pharmacokinetic analysis of daratumumab as monotherapy and as part of combination therapy, the mean central volume of distribution (Vd) values were 4.7 +/- 1.3 L and 4.4 +/- 1.5 L, respectively. The mean estimated terminal half-life value associated with linear clearance was 18 +/- 9 days following daratumumab monotherapy; the mean terminal half-life was similar following daratumumab as combination therapy. Daratumumab clearance decreased with increasing dose and repeated dosing. The mean linear clearance was 171.4 +/- 95.3 mL/day for monotherapy.[60311]

At the end of weekly dosing, the mean daratumumab Cmax level was about 2.7- to 3-times higher than the mean Cmax level following the first dose. Additionally, the mean Cmin level (trough) was 573 +/- 332 mcg/mL when daratumumab was administered as monotherapy and 502 +/- 196 mcg/mL to 607 +/- 231 mcg/mL when daratumumab was administered as part of combination therapy. In a population pharmacokinetic analysis in patients with multiple myeloma, steady-state levels were achieved at about 5 months after the daratumumab 16 mg/kg IV every 4-week dosing period (by the 21st infusion); the mean steady-state to first dose Cmax ratio was 1.6 (SD +/- 0.5). The AUC values increased more than dose-proportionally over the range of 1 to 24 mg/kg for monotherapy and 1 to 16 mg/kg for combination therapy. A week 1 day 1 split-dose infusion of 8 mg/kg IV resulted in a different pharmacokinetic profile in the first day compared with a single-dose infusion of 16 mg/kg; however, similar Cmax and Cmin concentrations occurred following the administration of the second 8 mg/kg split dose on week 1 day 2.[60311]

It is not known whether daratumumab is secreted in human milk or if it affects the breastfed child or milk production. It is known that human IgG is present in human milk; however, published data suggest that only small amounts of antibodies enter the neonatal and infant circulation. Advise women who are receiving daratumumab in combination with thalidomide or a thalidomide analog (e.g., lenalidomide and pomalidomide) to avoid breast-feeding due to the potential for serious adverse reactions in the breastfed child with this combination therapy.