Dosing & Uses
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/hyaluronidase
-
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/hyaluronidase
-
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/hyaluronidase
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/hyaluronidase
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/hyaluronidase
-
Combination therapy with pomalidomide and dexamethasone
- Indicated in combination with pomalidomide and dexamethasone for multiple myeloma in patients who have 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 with daratumumab/hyaluronidase
Combination therapy with carfilzomib and dexamethasone
- Indicated in combination with carfilzomib and dexamethasone for relapsed or refractory multiple myeloma in adults who have received 1-3 prior lines of 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/hyaluronidase
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (3)
- axicabtagene ciloleucel
daratumumab, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- 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
- brexucabtagene autoleucel
daratumumab, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
Monitor Closely (52)
- 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.
- cholera vaccine
daratumumab decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- 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.
- dengue vaccine
daratumumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- 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. .
- efgartigimod alfa
efgartigimod alfa will decrease the level or effect of daratumumab by receptor binding competition. Use Caution/Monitor. Coadministration of efgartigimod with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- 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.
- ponesimod
ponesimod and daratumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- 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. .
- siponimod
siponimod and daratumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- 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.
- ublituximab
ublituximab and daratumumab both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered
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.
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
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, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle-closure glaucoma; if ocular symptoms occur, interrupt therapy and seek immediate ophthalmologic evaluation prior to restarting treatment
- Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision
- 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
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.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
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)
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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
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