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
  • Combination therapy with bortezomib, thalidomide, and dexamethasone
    • Indicated in combination with bortezomib, thalidomide, and dexamethasone for multiple myeloma in newly diagnosed patients who are eligible for ASCT
    • Induction Weeks 1-8: 1,800 mg/30,000 units SC once weekly (total of 8 doses)
    • Induction Weeks 9-16: 1,800 mg/30,000 units SC q2Weeks (total of 4 doses); first dose of every-2-week dosing schedule is given at Week 9
    • Stop for high-dose chemotherapy and ASCT
    • Consolidation Weeks 1-8: 1,800 mg/30,000 units SC q2Weeks (total of 4 doses)
    • 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
  • Combination therapy with pomalidomide and dexamethasone
    • Indicated in combination with pomalidomide and dexamethasone for multiple myeloma in patients whohave received ≥1 prior therapy including lenalidomide and a proteasome inhibitor
    • 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 dosingschedule 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 withdaratumumab

Amyloidosis

Indicated in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain (AL) amyloidosis

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 give at Week 9

Week 25 and thereafter: 1,800 mg/30,000 units SC q4Weeks until disease progression or maximum of 2 years

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

Limitations of use

  • Light chain amyloidosis
    • Not indicated nor recommended for patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials

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

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (1)

              • beclomethasone, inhaled

                beclomethasone, inhaled will decrease the level or effect of hyaluronidase by unspecified interaction mechanism. Avoid or Use Alternate Drug. Larger hyaluronidase doses may be required to achieve desired effect

              Monitor Closely (46)

              • alprazolam

                hyaluronidase, alprazolam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • articaine

                hyaluronidase, articaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • aspirin

                aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • aspirin rectal

                aspirin rectal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • azelastine

                azelastine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • bazedoxifene/conjugated estrogens

                bazedoxifene/conjugated estrogens decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • brompheniramine

                brompheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • carbinoxamine

                carbinoxamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • cetirizine

                cetirizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • chloroprocaine

                hyaluronidase, chloroprocaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • chlorpheniramine

                chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • choline magnesium trisalicylate

                choline magnesium trisalicylate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • clemastine

                clemastine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • clonazepam

                hyaluronidase, clonazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • conjugated estrogens

                conjugated estrogens decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • conjugated estrogens, vaginal

                conjugated estrogens, vaginal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • corticotropin

                corticotropin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Corticotropin (ACTH), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • cortisone

                cortisone decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Cortisone, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • cyclizine

                cyclizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • cyproheptadine

                cyproheptadine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • dexbrompheniramine

                dexbrompheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • dexchlorpheniramine

                dexchlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • diazepam

                hyaluronidase, diazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • diflunisal

                diflunisal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • dimenhydrinate

                dimenhydrinate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • diphenhydramine

                diphenhydramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • doxylamine

                doxylamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • estradiol

                estradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estrogens conjugated synthetic

                estrogens conjugated synthetic decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estrogens esterified

                estrogens esterified decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estropipate

                estropipate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • ethinylestradiol

                ethinylestradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • furosemide

                hyaluronidase, furosemide. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • hydroxyzine

                hydroxyzine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • levocetirizine

                levocetirizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • lidocaine

                hyaluronidase, lidocaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • lorazepam

                hyaluronidase, lorazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • mometasone inhaled

                mometasone inhaled decreases effects of hyaluronidase by Other (see comment). Modify Therapy/Monitor Closely. Comment: Corticosteroids may decrease therapeutic effects of hyaluronidase.

              • mometasone topical

                mometasone topical decreases effects of hyaluronidase by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Patients receiving larger doses of corticosteriods may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required.

              • oxazepam

                hyaluronidase, oxazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • phenytoin

                hyaluronidase, phenytoin. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • promethazine

                promethazine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • salicylates (non-asa)

                salicylates (non-asa) decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • salsalate

                salsalate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • tetracaine

                hyaluronidase, tetracaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              Minor (4)

              • bupivacaine

                hyaluronidase, bupivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • mepivacaine

                hyaluronidase, mepivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • prilocaine

                hyaluronidase, prilocaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • ropivacaine

                hyaluronidase, ropivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

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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%)

              >10% (Light chain amyloidosis)

              All grades

              • Decreased lymphocytes (81%)
              • Decreased hemoglobin (66%)
              • Decreased leukocytes (60%)
              • Decreased platelets (46%)
              • Upper respiratory tract infection (40%)
              • Diarrhea (36%)
              • Constipation (34%)
              • Peripheral sensory neuropathy (31%)
              • Decreased neutrophils (30%)
              • Dyspnea (26%)
              • Cough (20%)
              • Pneumonia (15%)
              • Back pain (12%)
              • Arrhythmia (11%)
              • Injection site reactions (11%)

              Grade 3 or 4

              • Decreased lymphocytes (54%)

              1-10% (Newly diagnosed multiple myeloma)

              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%)

              1-10% (Light chain amyloidosis)

              All grades

              • Arthralgia (10%)
              • Muscle spasms (10%)

              Grade 3 or 4

              • Pneumonia (10%)
              • Decreased leukocytes (7%)
              • Decreased hemoglobin (6%)
              • Decreased neutrophils (6%)
              • Diarrhea, Grade 3 (6%)
              • Arrhythmia (4%)
              • Dyspnea (4%)
              • Peripheral sensory neuropathy, Grade 3 (3%)
              • Decreased platelets (3%)
              • Constipation, Grade 3 (2%)
              • Back pain (2%)
              • Muscle spasm (1%)
              • Cough, Grade 3 (1%)
              • Upper respiratory tract infection, Grade 3 (1%)

              <1% (Multiple Myeloma)

              Monotherapy

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

              Frequency Not Defined (Light chain amyloidosis)

              Skin and subcutaneous tissue disorders: Rash, pruritus

              Nervous system disorders: Paresthesia

              General disorders and administration site conditions: Infusion reaction, chills

              Cardiac disorders: Cardiac failure, cardiac arrest

              Metabolism and nutrition disorders: Hyperglycemia, hypocalcemia, dehydration

              Infections: Bronchitis, herpes zoster, sepsis, urinary tract infection, influenza, cytomegalovirus, listeriosis

              Vascular disorders: Hypertension

              Musculoskeletal and connective tissue disorders: Musculoskeletal chest pain

              Gastrointestinal disorders: Pancreatitis

              Respiratory, thoracic and mediastinal disorders: Pulmonary edema

              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

              Cardiac reactions with light chain (AL) amyloidosis

              • Serious or fatal cardiac adverse reactions reported
              • Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at greater risk
              • Patients with NYHA Class IIIB or IV disease were not studied
              • Monitor patients with cardiac involvement more frequently for cardiac adverse reactions; administer supportive care as appropriate

              Hypersensitivity and other administration reactions

              • 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 in combination with lenalidomide, thalidomide, or pomalidomide

              • Lenalidomide may cause birth defects and death of the unborn child; therefore, coadministration with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant females; refer to the lenalidomide, thalidomide, or pomalidomide, 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

              Because of potential for serious adverse reactions in the breastfed child when administered with lenalidomide, thalidomide, or pomalidomide, advise women not to breastfeed during treatment; refer to lenalidomide, thalidomide, or pomalidomide prescribing information for additional information

              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 hematopoietic cells, including clonal plasma cells in multiple myeloma cells and light chain (AL) amyloidosis, as well as other cell types

              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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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              • 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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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.