daratumumab (Rx)

Brand and Other Names:Darzalex
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for injection

  • 100mg/5mL vial
  • 400mg/20mL vial
  • Requires further dilution prior to administration

Multiple Myeloma

Monotherapy

  • Indicated as monotherapy for multiple myeloma in patients who have received at least 3 lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double-refractory to a PI and IMiD
  • Weeks 1-8: 16 mg/kg IV infusion once weekly
  • Weeks 9-24: 16 mg/kg IV infusion every 2 weeks
  • Week 25 onward until disease progression: 16 mg/kg IV infusion every 4 weeks

Combination therapy

  • Combination therapy with bortezomib and dexamethasone
    • Indicated in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy
    • Weeks 1-9: 16 mg/kg IV infusion once weekly
    • Weeks 10-24: 16 mg/kg IV infusion every 3 weeks
    • Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks
  • Combination therapy with lenalidomide and dexamethasone
    • Indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at 1 prior therapy
    • Weeks 1-8: 16 mg/kg IV infusion once weekly
    • Weeks 9-24: 16 mg/kg IV infusion every 2 weeks
    • Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks
  • Combination therapy with pomalidomide and dexamethasone
    • Indicated in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
    • Weeks 1-8: 16 mg/kg IV infusion once weekly
    • Weeks 9-24: 16 mg/kg IV infusion every 2 weeks
    • Week 25 onwards until disease progression: 16 mg/kg IV infusion every 4 weeks

Preinfusion and postinfusion medications required (see Administration)

Further dilution required (see Administration)

Dosage Modifications

Infusion reaction (see Administration)

Hematologic toxicity

  • No dose reductions are recommended
  • Dose delay may be required to allow recovery of blood cell counts

Renal impairment

  • No dosage adjustment required

Hepatic impairment

  • Mild (TB <ULN and AST 1-1.5 ULN, or TB 1-1.5 ULN and any AST): No dose adjustment required
  • Moderate-to-severe: Not studied

Diffuse Large B-cell Lymphoma (Orphan)

Orphan designation for treatment of diffuse large B-cell lymphoma

Sponsor

  • Janssen Research and Development, LLC; 1400 McKean Road, P. O. Box 776; Spring House, Pennsylvania 19477

Safety and efficacy not established

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Adverse Effects

Adverse reactions listed below are for any grade unless otherwise noted

>10%

Lymphopenia (72%)

Neutropenia (60%)

Infusion reaction (48%)

Thrombocytopenia (48%)

Anemia (45%)

Fatigue (39%)

Lymphopenia, grade 3 (30%)

Nausea (27%)

Back pain (23%)

Pyrexia (21%)

Cough (21%)

Upper respiratory tract infection (20%)

Anemia, grade 3 (19%)

Neutropenia, grade 3 (17%)

Nasal congestion (17%)

Arthralgia (17%)

Diarrhea (16%)

Constipation (15%)

Pain in extremity (15%)

Dyspnea (15%)

Nasopharyngitis (15%)

Decreased appetite (15%)

Vomiting (14%)

Musculoskeletal chest pain (12%)

Headache (12%)

Pneumonia (11%)

1-10%

Thrombocytopenia, grade 3 (10%)

Lymphopenia, grade 4 (10%)

Hypertension (10%)

Chills (10%)

Thrombocytopenia, grade 4 (8%)

Pneumonia, grade 3 (6%)

Hypertension, grade 3 (5%)

Neutropenia, grade 4 (3%)

Infusion reaction, grade 3 (3%)

Fatigue, grade 3 (2%)

Back pain, grade 3 (2%)

Pyrexia, grade 3 (1%)

Dyspnea, grade 3 (1%)

Pain in extremity, grade 3 (1%)

Musculoskeletal chest pain, grade 3 (1%)

Upper respiratory tract infection, grade 3 (1%)

Diarrhea, grade 3 (1%)

Decreased appetite, grade 3 (1%)

Headache, grade 3 (1%)

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Warnings

Contraindications

None

Cautions

May increase neutropenia and/or thrombocytopenia induced by background therapy; monitor CBC counts periodically during treatment; monitor patients with neutropenia for signs of infection; dose delay may be required to allow recovery of neutrophils; no dose reduction is recommended, consider supportive care with growth factors and/or transfusions

Binds to CD38 on RBCs and may result in a positive indirect antiglobulin test (Coombs test)

May cause false-positive results with serum protein electrophoresis (SPE) and immunofixation (IFE) assays

Severe infusion reactions

  • Severe infusion reactions reported in ~50% of all patients (most during the first infusion); may also occur with subsequent infusions
  • Nearly all reactions occurred during infusion or within 4 hr of completing infusion
  • Prior to the introduction of postinfusion medication in clinical trials, infusion reactions occurred up to 48 hr after infusion
  • Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension
  • Signs and symptoms may include respiratory symptoms (eg, cough, wheezing, larynx, throat tightness and irritation), laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis
  • Less common symptoms were hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills
  • Premedicate patients with antihistamines, antipyretics, and corticosteroids
  • Frequently monitor patients during the entire infusion
  • Permanently discontinue for life-threatening (grade 4) reactions
  • For grade 1, 2, or 3 reactions, reduce the infusion rate when restarting the infusion
  • To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions
  • Patients with a history of obstructive pulmonary disorders may require additional postinfusion medications to manage respiratory complications
  • Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with obstructive pulmonary disorders
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Pregnancy & Lactation

Pregnancy

There are no human data to inform a risk with use of daratumumab during pregnancy and animal studies have not been conducted

Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta

Based on its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density

Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed

Contraception

  • To avoid exposure to the fetus, women of reproductive potential should use effective contraception during treatment and for 3 months after discontinuing treatment

Lactation

Unknown if distributed in human breast milk

Human IgG is known to be present in human milk; published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Monoclonal antibody that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells

The binding to CD38 is believed to induce rapid tumor cell death through programmed cell death, or apoptosis, and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity

Absorption

Peak plasma concentration: 915 mcg/mL (weekly dosing)

Trough (predose) concentration: 573 mcg/mL (weekly dose)

Distribution

Vd: 4.7 L (at steady-state)

Elimination

Half-life: 18 days

Clearance: 171.4 mL/day (at steady-state)

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Administration

IV Preparation

Each vial is for single use only (does not contain preservatives)

Calculate the dose in mg and total volume in mL of daratumumab solution required and the number vials needed based on patient actual body weight

Check that the solution is colorless to pale yellow; do not use if opaque particles, discoloration, or other foreign particles are present

Using aseptic technique, remove a volume of 0.9% NaCl from the infusion bag/container that is equal to the required volume of daratumumab solution

Withdraw the daratumumab dose from the vial(s) and dilute to the appropriate volume by adding to the infusion bag/container containing 0.9% NaCl (first infusion 1000 mL; second and subsequent infusions 500 mL)

Infusion bags/containers must be made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP+PE)

Dilute under appropriate aseptic conditions

Discard any unused portion left in the vial

Gently invert the bag/container to mix the solution

Do not shake

Following dilution, the infusion bag/container may be stored for up to 24 hr in a refrigerator at 2-8ºC (36-46ºF); protect from light and do not freeze

After allowing the bag/container to come to room temperature, use immediately since the solution does not contain a preservative

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit

The diluted solution may develop very small, translucent-to-white proteinaceous particles, as daratumumab is a protein

Do not use if visibly opaque particles, discoloration, or foreign particles are observed

IV Administration

Should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion reactions if they occur

Administer the diluted solution by IV infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, nonpyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometer)

Polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE administration sets must be used

Infusion should be completed within 15 hr

Do not store any unused portion of the infusion solution for reuse

Any unused product or waste material should be disposed of in accordance with local requirements

Do not infuse concomitantly in the same IV line with other agents

Concomitant medications

  • Preinfusion medications
    • Premedicate patients with antihistamines, antipyretics, and corticosteroids 1 hr before every infusion
    • PO antipyretics (acetaminophen 650-1000 mg), plus
    • PO or IV antihistamine (diphenhydramine 25-50 mg or equivalent), plus
    • Monotherapy: IV corticosteroid (methylprednisolone 100 mg, or equivalent dose of an intermediate-acting or long-acting corticosteroid); following the second infusion, the dose of corticosteroid may be reduced (methylprednisolone 60 mg IV), OR
    • Combination therapy: Dexamethasone 20 mg before every daratumumab infusion; given IV before first daratumumab infusion and oral administration may be considered prior to subsequent infusion
  • Postinfusion medications (monotherapy)
    • To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions
    • PO corticosteroid (20 mg methylprednisolone or equivalent dose of a corticosteroid in accordance with local standards) on the first and second day after all infusions
    • History of COPD: Consider prescribing postinfusion medications (eg, short- and long-acting bronchodilators, and inhaled corticosteroids); after the first 4 infusions, if the patient experiences no major infusion reactions, these additional inhaled postinfusion medications may be discontinued
  • Postinfusion medications (combination therapy)
    • Consider administering low-dose oral methylprednisolone (≤20 mg) or equivalent, the day after daratumumab infusion
    • However, if a background regimen-specific corticosteroid (eg, dexamethasone) is administered the day after, additional postinfusion medications may not be needed
  • Herpes zoster reactivation prophylaxis
    • Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week of starting daratumumab and continue for 3 months following treatment

Infusion rate

  • Consider incremental escalation only in the absence of infusion reactions with the previous infusion
  • First infusion (1000 mL dilution): 50 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr
  • Second infusion (500 mL dilution): 50 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr
  • Subsequent infusions (500 mL dilution): 100 mL/hr for first hour; may increase by 50 mL/hr every hour, not to exceed 200 mL/hr

Infusion reactions

  • For infusion reactions of any grade/severity, immediately interrupt the infusion, and manage symptoms
  • Management of infusion reactions may further require reduction in the rate of infusion, or treatment discontinuation
  • 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 no further reaction symptoms experienced, infusion rate escalation may resume at increments and intervals as clinically appropriate up to a maximum of 200 mL/hr
  • Grade 3 (severe)
    • Once reaction symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred
    • If no further reaction symptoms experienced, infusion rate escalation may resume at increments and intervals outlined in Administration section
    • Repeat the procedure above in the event of recurrence of additional episodes
    • Permanently discontinue upon the third occurrence of a ≥grade 3 infusion reaction
  • Grade 4 (life threatening)
    • Permanently discontinue treatment

Missed dose

  • If a planned dose is missed, administer the dose as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval

Storage

Unopened vials

  • Does not contain a preservative
  • Refrigerate at 2-8ºC (36-46ºF)
  • Protect from light
  • Do not freeze
  • Do not shake

Diluted solution

  • Since drug does not contain a preservative, administer the diluted solution immediately at room temperature 15-25°C (59-77°F) and in room light
  • Diluted solution may be kept at room temperature for a maximum of 15 hr (including infusion time)
  • If not used immediately
    • May store for up to 24 hr in a refrigerator at 2-8ºC (36-46ºF)
    • Protect from light
    • Do not freeze
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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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