daratumumab/hyaluronidase (Rx)

Brand and Other Names:Darzalex Faspro, daratumumab/hyaluronidase-fihj
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

daratumumab/hyaluronidase

injectable solution

  • (1,800mg/30,000 units)/15mL
  • Ready-to-use SC solution contains daratumumab and hyaluronidase human

Multiple Myeloma

Newly diagnosed multiple myeloma

  • Combination therapy with bortezomib, melphalan, and prednisone
    • Indicated in combination with bortezomib, melphalan, and prednisone for multiple myeloma in newly diagnosed patients who are ineligible for autologous stem cell transplant (ASCT)
    • Weeks 1-6: 1,800 mg/30,000 units SC once weekly (total of 6 doses)
    • Weeks 7-54: 1,800 mg/30,000 units SC q3Weeks (total of 16 doses); first dose of the every-3-week dosing schedule is given at Week 7
    • Week 55 onwards until disease progression: 1,800 mg/30,000 units SC q4Weeks; first dose of the every-4-week dosing schedule is given at Week 55
    • See prescribing information for chemotherapy agents doses administered in combination with daratumumab
  • Combination therapy with lenalidomide and dexamethasone
    • Indicated in combination with lenalidomide and dexamethasone for multiple myeloma in newly diagnosed patients who are ineligible for ASCT
    • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
    • Weeks 9-24: 1,800 mg/30,000 units SC q2Weeks (total of 8 doses); first dose of every-2-week dosing schedule is given at Week 9
    • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC q4Weeks; first dose of every-4-week dosing schedule is given at Week 25
    • See prescribing information for chemotherapy agents doses administered in combination with daratumumab

Relapsed or refractory multiple myeloma

  • Monotherapy
    • Indicated for multiple myeloma in patients who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
    • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
    • Weeks 9-24: 1,800 mg/30,000 units SC q2Weeks (total of 8 doses); first dose of every-2-week dosing schedule is given at Week 9
    • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC q4Weeks; first dose of every-4-week dosing schedule is given at Week 25
  • Combination therapy with lenalidomide and dexamethasone
    • Indicated in combination with lenalidomide and dexamethasone for multiple myeloma in patients with relapsed or refractory multiple myeloma who have received ≥1 prior therapy
    • Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
    • Weeks 9-24: 1,800 mg/30,000 units SC q2Weeks (total of 8 doses); first dose of every-2-week dosing schedule is given at Week 9
    • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC q4Weeks; first dose of every-4-week dosing schedule is given at Week 25
    • See prescribing information for chemotherapy agents doses administered in combination with daratumumab
  • Combination therapy with bortezomib and dexamethasone
    • Indicated in combination with bortezomib and dexamethasone for multiple myeloma in patients who have received ≥1 prior therapy
    • Weeks 1-9: 1,800 mg/30,000 units SC once weekly (total of 9 doses)
    • Weeks 10-24: 1,800 mg/30,000 units SC q3Weeks (total of 5 doses); first dose of the every-3-week dosing schedule is given at Week 10
    • Week 25 onwards until disease progression: 1,800 mg/30,000 units SC q4Weeks; first dose of the every-4-week dosing schedule is given at Week 25
    • See prescribing information for chemotherapy agents doses administered in combination with daratumumab

Dosage Modifications

No dose reductions are recommended

If myelosuppression occurs, consider withholding dose

Renal impairment

  • CrCl 15-89 mL: No clinically meaningful effect on pharmacokinetics of daratumumab

Hepatic impairment

  • Mild (total bilirubin 1-1.5x ULN and AST >ULN): No clinically meaningful effect on pharmacokinetics of daratumumab
  • Moderate-to-severe: Daratumumab pharmacokinetics are unknown

Dosing Considerations

Notify blood transfusion centers of the interference with serological testing and inform blood banks that a patient has received daratumumab; type and screen patient before starting treatment

Safety and efficacy not established

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Interactions

Interaction Checker

and daratumumab/hyaluronidase

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (Newly diagnosed multiple myeloma)

            Combination with bortezomib, melphalan, and prednisone

            • All grades
              • Decreased leukocytes (96%)
              • Decreased lymphocytes (93%)
              • Decreased platelets (93%)
              • Decreased neutrophils (88%)
              • Decreased hemoglobin (48%)
              • Upper respiratory tract infection (39%)
              • Constipation (37%)
              • Nausea (36%)
              • Fatigue (36%)
              • Pyrexia (34%)
              • Peripheral sensory neuropathy (34%)
              • Diarrhea (33%)
              • Cough (24%)
              • Insomnia (22%)
              • Back pain (21%)
              • Vomiting (21%)
              • Bronchitis (16%)
              • Pneumonia (15%)
              • Decreased appetite (15%)
              • Rash (13%)
              • Hypertension (13%)
              • Abdominal pain (13%)
              • Peripheral edema (13%)
              • Pruritus (12%)
              • Musculoskeletal chest pain (12%)
            • Grade 3 or 4
              • Decreased lymphocytes (84%)
              • Decreased leukocytes (52%)
              • Decreased neutrophils (49%)
              • Decreased platelets (42%)
              • Decreased hemoglobin (19%)

            Combination with lenalidomide and dexamethasone

            • All grades
              • Decreased leukocytes (94%)
              • Decreased neutrophils (89%)
              • Decreased platelets (86%)
              • Decreased lymphocytes (82%)
              • Fatigue (52%)
              • Decreased hemoglobin (45%)
              • Diarrhea (45%)
              • Upper respiratory tract infection (43%)
              • Muscle spasm (31%)
              • Constipation (26%)
              • Pneumonia (23%)
              • Pyrexia (23%)
              • Dyspnea (22%)
              • Peripheral edema (18%)
              • Peripheral sensory neuropathy (17%)
              • Insomnia (17%)
              • Bronchitis (14%)
              • Cough (14%)
              • Back pain (14%)
              • Nausea (12%)
              • Hyperglycemia (12%)
              • Hypocalcemia (11%)
              • Vomiting (11%)
              • Urinary tract infection (11%)
            • Grade 3 or 4
              • Decreased lymphocytes (58%)
              • Decreased neutrophils (52%)
              • Decreased leukocytes (34%)
              • Pneumonia (17%)

            Monotherapy

            • All grades
              • Decreased leukocytes (65%)
              • Decreased lymphocytes (59%)
              • Decreased neutrophils (55%)
              • Decreased platelets (43%)
              • Decreased hemoglobin (42%)
              • Upper respiratory tract infection (24%)
              • Diarrhea (15%)
              • Fatigue (15%)
              • Infusion reactions (13%)
              • Pyrexia (13%)
            • Grade 3 or 4
              • Decreased lymphocytes (36%)
              • Decreased leukocytes (19%)
              • Decreased neutrophils (19%)
              • Decreased platelets (16%)
              • Decreased hemoglobin (14%)

            1-10%

            Combination with bortezomib, melphalan, and prednisone

            • All grades
              • Dizziness (10%)
              • Hypotension (10%)
              • Infusion reaction (<10%)
              • Injection site reaction (<10%)
              • Chills (<10%)
              • Herpes zoster (<10%)
              • Urinary tract infection (<10%)
              • Influenza (<10%)
              • Sepsis (<10%)
              • Arthralgia (<10%)
              • Muscle spasms (<10%)
              • Headache (<10%)
              • Paresthesia (<10%)
              • Dyspnea (<10%)
              • Pulmonary edema (<10%)
              • Atrial fibrillation (<10%)
            • Grade 3 or 4
              • Pneumonia (7%)
              • Hypertension (6%)
              • Diarrhea (3%)
              • Fatigue (3%)
              • Insomnia (3%)
              • Back pain (3%)
              • Hypotension (3%)
              • Peripheral edema (1%)
              • Peripheral sensory neuropathy (1%)
              • Decreased appetite (1%)

            Combination with lenalidomide and dexamethasone

            • All grades
              • Arthralgia (<10%)
              • Musculoskeletal chest pain (<10%)
              • Dizziness (<10%)
              • Headache (<10%)
              • Paresthesia (<10%)
              • Rash (<10%)
              • Pruritus (<10%)
              • Abdominal pain (<10%)
              • Influenza (<10%)
              • Sepsis (<10%)
              • Herpes zoster (<10%)
              • Decreased appetite (<10%)
              • Atrial fibrillation (<10%)
              • Chills (<10%)
              • Infusion reaction (<10%)
              • Injection site reaction (<10%)
              • Hypotension (<10%)
              • Hypertension (<10%)
            • Grade 3 or 4
              • Hyperglycemia (9%)
              • Decreased platelets (9%)
              • Decreased hemoglobin (8%)
              • Fatigue (5%)
              • Diarrhea (5%)
              • Insomnia (5%)
              • Peripheral edema (3%)
              • Dyspnea (3%)
              • Upper respiratory tract infection (3%)
              • Peripheral sensory neuropathy (2%)
              • Muscle spasms (2%)
              • Bronchitis (2%)
              • Pyrexia (2%)
              • Constipation (2%)

            Monotherapy

            • All grades
              • Injection site reactions (<10%)
              • Peripheral edema (<10%)
              • Arthralgia (<10%)
              • Musculoskeletal chest pain (<10%)
              • Muscle spasm (<10%)
              • Constipation (<10%)
              • Vomiting (<10%)
              • Abdominal pain (<10%)
              • Decreased appetite (<10%)
              • Hyperglycemia (<10%)
              • Hypocalcemia (<10%)
              • Dehydration (<10%)
              • Insomnia (<10%)
              • Hypertension (<10%)
              • Hypotension (<10%)
              • Dizziness (<10%)
              • Peripheral sensory neuropathy (<10%)
              • Paresthesia (<10%)
              • Bronchitis (<10%)
              • Influenza (<10%)
              • Urinary tract infection (<10%)
              • Herpes zoster (<10%)
              • Sepsis (<10%)
              • Hepatitis B reactivation (<10%)
              • Pruritus (<10%)
              • Rash (<10%)
              • Atrial fibrillation (<10%)
              • Pulmonary edema (<10%)
              • Cough (9%)
              • Pneumonia (8%)
              • Nausea (8%)
              • Chills (6%)
              • Dyspnea (6%)
            • Grade 3 or 4
              • Pneumonia (5%)
              • Infusion reactions (2%)
              • Back pain (2%)
              • Diarrhea (1%)
              • Fatigue (1%)
              • Upper respiratory tract infection (1%)
              • Cough (1%)
              • Dyspnea (1%)

            <1%

            Monotherapy

            • Grade 3 or 4
              • Chills (0.4%)
              • Nausea (0.4%)

            Postmarketing Reports

            Immune System: Anaphylactic reaction

            Gastrointestinal: Pancreatitis

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            Warnings

            Contraindications

            Severe hypersensitivity to daratumumab, hyaluronidase, or any other components

            Cautions

            May increase neutropenia and/or thrombocytopenia induced by background therapy; monitor CBC count periodically during treatment; consider withholding dose to allow recovery of neutrophils and/or thrombocytopenia

            Can cause fetal harm

            Hypersensitivity and other administration reactions

            • Injection-site reactions reported; local reactions occurred a median of 7 minutes after starting administration
            • Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur
            • Severe reactions included hypoxia, dyspnea, hypertension, and tachycardia
            • Premedicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids
            • Monitor for local or systemic administration-related reactions, especially following the first or second injection
            • Permanently discontinue for life-threatening reactions

            Drug interaction overview

            May cause false-positive results with serum protein electrophoresis and immunofixation assays

            Interference with cross-matching and red blood cell antibody screening
            • Binds to CD38 on red blood cells and may result in a positive indirect antiglobulin test (Coombs test)
            • Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration
            • Determination of a patient’s ABO and Rh blood type are not impacted
            • Type and screen patients prior to starting treatment
            • Inform blood banks that a patient has received daratumumab
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            Pregnancy & Lactation

            Pregnancy

            Based on mechanism of action and animal data, fetal harm may occur when administered to pregnant females

            No data available on use in pregnant females to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal reproduction studies not conducted

            Treated with daratumumab with lenalidomide

            • Lenalidomide may cause birth defects and death of the unborn child; therefore, combination of daratumumab and lenalidomide is contraindicated in pregnant females; refer to the lenalidomide prescribing information on use during pregnancy and contraception
            • Test females of reproductive potential prior to initiating treatment

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 3 months after final dose

            Clinical considerations

            • IgG1 monoclonal antibodies are transferred across the placenta

            Lactation

            No data available on the presence of daratumumab and hyaluronidase in human breast milk, effects on breastfeeding, or milk production

            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

            Binding to CD38 induces 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

            Hyaluronidase human increases permeability of SC tissue by temporarily depolymerizing hyaluronan

            Absorption

            Peak plasma concentration: 592 mcg/mL (SC); 688 mcg/mL (IV)

            AUC: 4,017 mcg⋅day/mL (SC); 4,019 mcg⋅day/mL (IV)

            Peak plasma time: ~3 days (SC)

            Absolute bioavailability: 69%

            Body weight

            • After SC administration as monotherapy, the mean maximum plasma trough after the 8th dose was 12% lower in the higher body weight (BW) group (>85 kg), while the mean maximum plasma trough was 81% higher in the lower BW group (≤50 kg) compared with the corresponding BW groups in IV daratumumab arm

            Distribution

            Vd: 3.8 L (peripheral); 5.2 L (central)

            Elimination

            Clearance: 119 mL/day

            Half-life: 20 days

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            Administration

            Recommended Concomitant Medications

            Premedication

            • Administer 1-3 hr before each dose
            • Do not administer background regimen-specific corticosteroids (eg, prednisone) on administration day when patients have received dexamethasone (or equivalent) as a premedication
            • Monotherapy
              • Acetaminophen 650-1,000 mg PO, plus
              • Diphendydramine 25-50 mg PO/IV or equivalent, plus
              • Methylprednisolone 100 mg (or equivalent) PO/IV; consider reducing methylprednisolone dose to 60 mg (or equivalent) following the second SC dose
            • Combination therapy
              • Acetaminophen 650-1000 mg PO, plus
              • Diphendydramine 25-50 mg PO/IV or equivalent, plus
              • Administer dexamethasone 20 mg (or equivalent) PO/IV
              • When dexamethasone is the background regimen-specific corticosteroid, dexamethasone dose that is part of the background regimen serves as premedication on administration day

            Postmedication

            • Administer after administering SC dose
            • If no major systemic administration-related reaction occurs after the first 3 doses, consider discontinuing corticosteroids (excluding any background regimen-specific corticosteroid)
            • Monotherapy
              • Methylprednisone 20 mg PO (or equivalent dose of an intermediate- or long-acting corticosteroid) for 2 days starting the day after administration
            • Combination therapy
              • Methylprednisolone ≤20 mg (or equivalent dose of an intermediate- or long-acting corticosteroid) beginning day after administration
              • If a background regimen-specific corticosteroid (eg, dexamethasone, prednisone) is administered the day after the infusion, additional corticosteroids may not be needed

            History of COPD

            • Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids; following the first 4 infusions if no administration-related reactions occur, consider discontinuing inhaled medications

            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

            SC Preparation

            Solution for SC is ready to use

            Remove vial from refrigerator and equilibrate to room temperature

            Withdraw 15 mL from vial into a syringe

            Compatible with polypropylene or polyethylene syringe material; polypropylene, polyethylene, or polyvinyl chloride (PVC) SC infusion sets; and stainless steel transfer and injection needles

            Visually inspect solution for particulates; solution should appear as a clear-to-opalescent and colorless-to-yellowish liquid

            SC Administration

            SC use only; do not administer IV

            Administer SC over ~3-5 minutes

            Injection site: Administer into subcutaneous tissue of the abdomen ~3 inches (7.5 cm) to the right or left of the navel

            No data are available on performing the injection at other sites of the body

            Rotate injection sites for successive injections

            Never inject into areas where the skin is red, bruised, tender, hard, or areas where there are scars

            Pause or slow down delivery rate if the patient experiences pain; if pain not alleviated by pausing or slowing down delivery rate, select a second injection site on opposite side of abdomen to deliver remaining dose

            Administer medications before and after SC administration to minimize administration-related reactions

            Missed dose: Administer as soon as possible and adjust dosing schedule to maintain dosing interval

            Storage

            Unopen vial

            • Refrigerate at 2-8ºC (36-46ºF) in the original carton to protect from light; do not freeze or shake
            • When vial removed from refrigerator to ambient temperature (15-30ºC [59-86ºF]); store unopened vial at ambient temperature and ambient light for up to 24 hr; keep out of direct sunlight

            Syringe containing daratumumab

            • If not used immediately, store solution for up to 4 hr at ambient temperature and ambient light; discard after 4 hours, if not used
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            Formulary

            FormularyPatient Discounts

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

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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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