Version May 2024
Note: Type and screen (blood type) prior to daratumumab initiation. Do not substitute daratumumab (IV) with daratumumab/hyaluronidase (for SUBQ use); products have different dosing and are not interchangeable.
Premedication: Premedicate 1 to 3 hours prior to each infusion with a corticosteroid, an oral antipyretic, and an oral or IV antihistamine (see "Premedications" below). Postinfusion, administer an oral corticosteroid to all patients to reduce the risk of delayed infusion reactions (see multiple myeloma "Postinfusion Medications" below).
Prophylaxis: To prevent herpes zoster reactivation, initiate antiviral prophylaxis within 1 week after starting daratumumab and continue for 3 months following completion of daratumumab treatment.
The initial daratumumab dose for multiple myeloma (16 mg/kg on week 1) may be divided over 2 consecutive days (by administering 8 mg/kg/day on days 1 and 2 of week 1 of therapy) to facilitate administration.
Multiple myeloma:
Multiple myeloma, newly diagnosed: Note: Daratumumab dosing should be based on actual body weight. Refer to specific protocol or to dexamethasone, lenalidomide, thalidomide, bortezomib, melphalan, and/or prednisone monographs for dosing when used in combination with daratumumab.
In combination with bortezomib, melphalan, and prednisone (D-VMP regimen; in patients ineligible for autologous stem cell transplant) (Ref):
Weeks 1 to 6: IV: 16 mg/kg once weekly for 6 doses.
Weeks 7 to 54: IV: 16 mg/kg once every 3 weeks for 16 doses.
Weeks 55 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with lenalidomide and low-dose dexamethasone (DRd regimen; in patients ineligible for autologous stem cell transplant) (Ref):
Weeks 1 to 8: IV: 16 mg/kg once weekly for 8 doses.
Weeks 9 to 24: IV: 16 mg/kg once every 2 weeks for 8 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with thalidomide, bortezomib, and dexamethasone (DVTd regimen; in patients eligible for autologous stem cell transplant) (Ref):
Induction:
Weeks 1 to 8: IV: 16 mg/kg once weekly for 8 doses.
Weeks 9 to 16: IV: 16 mg/kg once every 2 weeks for 4 doses.
Consolidation (following autologous stem cell transplant):
Weeks 1 to 8: IV: 16 mg/kg once every 2 weeks for 4 doses.
Multiple myeloma, relapsed/refractory: Note: Daratumumab dosing should be based on actual body weight. Refer to specific protocol or to dexamethasone, lenalidomide, bortezomib, carfilzomib, and/or pomalidomide monographs for dosing when used in combination with daratumumab.
Monotherapy:
Weeks 1 to 8: IV: 16 mg/kg once weekly for 8 doses.
Weeks 9 to 24: IV: 16 mg/kg once every 2 weeks for 8 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with lenalidomide and low-dose dexamethasone (DRd regimen (Ref)):
Weeks 1 to 8: IV: 16 mg/kg once weekly for 8 doses.
Weeks 9 to 24: IV: 16 mg/kg once every 2 weeks for 8 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with pomalidomide and low-dose dexamethasone (DPd regimen (Ref)):
Weeks 1 to 8: IV: 16 mg/kg once weekly for 8 doses.
Weeks 9 to 24: IV: 16 mg/kg once every 2 weeks for 8 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with bortezomib and dexamethasone (DVd regimen (Ref)):
Weeks 1 to 9: IV: 16 mg/kg once weekly for 9 doses.
Weeks 10 to 24: IV: 16 mg/kg once every 3 weeks for 5 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
In combination with carfilzomib and dexamethasone (DKd regimen (Ref)):
Week 1: IV: 8 mg/kg on days 1 and 2.
Weeks 2 to 8: IV: 16 mg/kg once weekly for 7 doses.
Weeks 9 to 24: IV: 16 mg/kg once every 2 weeks for 8 doses.
Weeks 25 and beyond: IV: 16 mg/kg once every 4 weeks until disease progression.
Missed dose: If a dose is missed, administer as soon as possible and adjust the schedule accordingly (maintain the treatment interval).
Premedications for multiple myeloma: Administer 1 to 3 hours prior to each daratumumab infusion. If dexamethasone is the background regimen-specific corticosteroid, the dexamethasone treatment dose will serve as the corticosteroid premedication on daratumumab infusion days. Do not administer additional background regimen-specific corticosteroids (eg, prednisone) on daratumumab infusion days when patients receive dexamethasone (or equivalent) as a premedication.
Corticosteroid:
Monotherapy: Methylprednisolone 100 mg IV (or equivalent intermediate- or long-acting corticosteroid); following the second infusion, consider reducing the dose (eg, methylprednisolone 60 mg [IV or oral] or equivalent).
Combination therapy: Dexamethasone 20 mg IV or orally (or equivalent) prior to each daratumumab infusion
plus
Antipyretic: Acetaminophen 650 to 1,000 mg orally plus
Antihistamine: Diphenhydramine 25 to 50 mg IV or orally or equivalent.
The following premedication regimens have also been reported:
First infusion: Acetaminophen 325 to 1,000 mg orally, diphenhydramine 25 to 50 mg orally or IV, dexamethasone 20 mg IV, montelukast 10 mg orally, ± famotidine 20 mg IV (Ref).
Subsequent infusions: Acetaminophen 325 to 1,000 mg orally, diphenhydramine 25 to 50 mg IV or orally, ± dexamethasone 20 mg IV (Ref).
Postinfusion medication:
Monotherapy: Administer methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long-acting corticosteroid) orally for 2 days starting the day after each daratumumab administration.
Combination therapy: Consider administering oral methylprednisolone at ≤20 mg (or equivalent intermediate- or long-acting corticosteroid) beginning the day after each daratumumab infusion. If dexamethasone or prednisone is administered the day after the daratumumab infusion as part of background combination chemotherapy regimen, additional postinfusion corticosteroid therapy may not be necessary.
Patients with a history of chronic obstructive pulmonary disease: Also consider short- and long-acting bronchodilators and inhaled corticosteroids postinfusion. If no major infusion reactions occur during the first 4 daratumumab infusions, consider discontinuing these additional inhaled postinfusion medications.
Systemic light chain amyloidosis, relapsed (off-label use): IV: Note: Refer to references/protocols for premedications, infusion time, and other additional details.
Cycles 1 and 2 (each cycle is 4 weeks): 16 mg/kg once weekly (as a single agent) for 8 doses (Ref).
Cycles 3 to 6 (each cycle is 4 weeks): 16 mg/kg once every 2 weeks (as a single agent) for 8 doses (Ref).
Cycle 7 and beyond: 16 mg/kg once every 4 weeks thereafter (as a single agent) until disease progression or unacceptable toxicity, for up to 24 months (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Theoretically, daratumumab's large molecular weight (145,400 daltons) precludes the drug from being efficiently filtered at the glomerulus or by dialysis filters; hence, dose adjustments for kidney dysfunction and/or kidney replacement therapies should generally be unnecessary (Ref). Patients with moderate to severe chronic kidney disease or receiving kidney replacement therapies should be closely monitored for characteristic toxicities of patients with kidney impairment receiving immunosuppression, such as hematologic toxicities and infection (Ref).
Altered kidney function: IV: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref):
IV: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Ref): IV: No dosage adjustment or supplemental dose necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed: IV: No dosage adjustment necessary (Ref).
CRRT: IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (Ref).
Mild (total bilirubin 1 to 1.5 times ULN or AST > ULN) or moderate (total bilirubin 1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling, however, mild or moderate impairment did not have any meaningful effect on daratumumab pharmacokinetics.
Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Note: Refer to specific protocol or to dexamethasone, prednisone, lenalidomide, thalidomide, bortezomib, carfilzomib, melphalan, or pomalidomide monographs for dosing adjustment for toxicity when used in combination with daratumumab.
Hematologic toxicity: No dose reductions of daratumumab are recommended; consider withholding daratumumab infusion to allow for neutrophil and/or platelet recovery.
Infusion reactions: Immediately interrupt daratumumab infusion for reaction of any severity. Manage symptoms as clinically appropriate.
Grade 1 or 2 (mild to moderate) infusion reaction: Once symptoms resolve, resume the daratumumab infusion at no more than 50% of the rate at which the reaction occurred. If no further reactions are observed, may escalate the infusion rate as appropriate up to the maximum rate of 200 mL/hour (see "Administration").
Grade 3 (severe) infusion reaction: Once symptoms resolve, consider resuming the daratumumab infusion at no more than 50% of the rate at which the reaction occurred. If no further reactions are observed, may escalate the infusion rate as appropriate (see "Administration"). If a grade 3 reaction recurs, repeat the steps above. Permanently discontinue daratumumab if a grade 3 infusion reaction occurs for the third time.
Grade 4 (anaphylactic reaction or life-threatening) infusion reaction: Permanently discontinue daratumumab.
Ocular reactions (eg, acute myopia, anterior chamber angle narrowing, ciliochoroidal effusions): Interrupt daratumumab infusion; ophthalmologic exam recommended prior to reinitiation of therapy.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for monotherapy in adults.
>10%:
Gastrointestinal: Constipation (15%), decreased appetite (15%), diarrhea (16%; grade 3: 1%), nausea (27%), vomiting (14%)
Hematologic & oncologic: Anemia (45%; grade 3: 19%), lymphocytopenia (72%; grade 3: 30%; grade 4: 10%), neutropenia (60%; grade 3: 17%; grade 4: 3%), thrombocytopenia (48%; grade 3: 10%; grade 4: 8%)
Nervous system: Fatigue (39%), headache (12%)
Neuromuscular & skeletal: Arthralgia (17%), back pain (23%), limb pain (15%), musculoskeletal chest pain (12%)
Respiratory: Cough (21%), dyspnea (15%), nasal congestion (17%), nasopharyngitis (15%), pneumonia (11%), upper respiratory tract infection (20%)
Miscellaneous: Fever (21%), infusion related reaction (48%; including severe infusion related reaction)
1% to 10%:
Cardiovascular: Hypertension (10%)
Infection: Herpes zoster infection (3%)
Nervous system: Chills (10%)
Miscellaneous: Physical health deterioration (3%)
<1%:
Immunologic: Antibody development (including neutralizing)
Infection: Reactivation of HBV
Frequency not defined:
Hematologic & oncologic: Positive indirect Coombs test
Ophthalmic: Acute angle-closure glaucoma, choroidal effusion (ciliochoroidal), myopia (acute)
Postmarketing:
Gastrointestinal: Pancreatitis
Hypersensitivity: Anaphylaxis
Infection: Cytomegalovirus disease, listeriosis
History of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Daratumumab may increase neutropenia and thrombocytopenia when used in combination with other chemotherapy agents for the treatment of multiple myeloma. Lymphopenia, neutropenia, thrombocytopenia, and anemia (including grade 3 and 4 toxicity) were commonly reported as treatment emergent adverse reactions in clinical trials.
• Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation has been reported rarely; some cases have been fatal.
• Infusion reactions: Severe and/or serious infusion reactions may occur (including anaphylactic reactions, bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular reactions [eg, choroidal effusion, acute myopia, acute angle closure glaucoma]), mostly during the first infusion; may be fatal or life-threatening. Signs and symptoms include cough, throat irritation, and nasal congestion, as well as chills, vomiting, and nausea. Less commonly reported signs and symptoms include wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision. Most infusion reactions were grade 1 or 2. Reactions may also be seen during subsequent infusions; <1% of patients experienced grade 3 or 4 reaction at week 2 or subsequent infusions. The median duration of infusions (when the dose was not split over 2 days) was ~7, 4, and 3 hours for the week 1, week 2, and subsequent infusions, respectively. Infusion reactions generally occur either during the infusion or within 4 hours of completion; some reactions occurred up to 48 hours after the infusion. Across several clinical trials (including monotherapy and combination therapy), the median time to onset of infusion reactions was 1.5 hours (range: up to 73 hours); approximately one-third of infusions were modified due to infusion reactions. Following daratumumab therapy interruption for autologous stem cell transplant (ASCT), the incidence of infusion reaction was ~11% when reinitiating daratumumab (at the infusion rate/dilution used prior to transplant); symptoms/severity were consistent with week 2 incidences prior to ASCT. Premedication with antihistamines, antipyretics, and corticosteroids is required. Administer in a facility with immediate access to resuscitative measures (eg, glucocorticoids, epinephrine, bronchodilators, oxygen). Administer oral corticosteroids to all patients after daratumumab infusion to reduce the risk of delayed infusion reactions.
Disease-related concerns:
• Interference with determination of myeloma response: Daratumumab (a human IgG kappa monoclonal antibody) may be detected on serum protein electrophoresis and immunofixation assays that monitor for endogenous M-protein. Interference with these assays by daratumumab may affect the determination of complete response and disease progression in some patients with IgG kappa myeloma protein.
Special populations:
• Older adult: Patients ≥65 years of age experienced a higher incidence of serious adverse reactions, including pneumonia and sepsis.
Other warnings/precautions:
• Do not interchange: Daratumumab (for IV administration) and daratumumab/hyaluronidase (for subcutaneous administration) have different dosing and are not interchangeable.
• Interference with serological testing: Through binding to CD38 on RBCs, daratumumab use may result in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated Coombs test positivity may persist for up to 6 months after the last infusion. In addition, daratumumab (bound to RBCs) masks antibody detection to minor antigens in the patient's serum; ABO and Rh blood type determination are not affected. Notify blood transfusion centers and blood banks that a patient has received daratumumab, and type and screen patients prior to initiation of daratumumab treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Darzalex: 100 mg/5 mL (5 mL); 400 mg/20 mL (20 mL)
No
Solution (Darzalex Intravenous)
100 mg/5 mL (per mL): $160.56
400 mg/20 mL (per mL): $160.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Darzalex: 100 mg/5 mL (5 mL); 400 mg/20 mL (20 mL) [contains mouse (murine) and/or hamster protein]
Note: Check label to ensure appropriate product is administered (daratumumab [IV] and daratumumab/hyaluronidase [SubQ] are different products and are not interchangeable).
IV: For IV infusion only. Do not administer IV push or as a bolus. Premedicate with a corticosteroid, acetaminophen, and an IV or oral antihistamine (see "Dosing") 1 to 3 hours prior to administration. Infuse in an environment equipped to monitor for and manage infusion reactions. Administer with an infusion set fitted with a flow regulator and with an inline, sterile, nonpyrogenic, low protein-binding polyethersulfone filter (0.22 or 0.2 micrometer). Polyurethane, polybutadiene, polyvinylchloride, polypropylene, or polyethylene administration sets are required. Do not mix with or infuse with other medications.
The manufacturer recommends not exceeding first, second, and subsequent infusion rates listed below. Begin infusion immediately after infusion bag reaches room temperature (if refrigerated). Infusion should be completed within 15 hours. Interrupt infusion for any severity of infusion reaction; if the reaction resolves, may resume infusion (see "Dosage Adjustment for Toxicity"). If infusion cannot be completed, do not save unused portion for reuse. Postinfusion, administer an oral corticosteroid to all patients to reduce the risk of delayed infusion reactions (see "Dosing"). In patients with a history of obstructive pulmonary disorder, consider short- and long-acting bronchodilators and inhaled corticosteroids postinfusion.
Infusion rate (multiple myeloma):
Week 1 infusion (500 mL [split-dose infusion; 8 mg/kg on days 1 and 2] or 1,000 mL volume [single-dose infusion; 16 mg/kg on day 1]): Infuse at 50 mL/hour for the first hour. If no infusion reactions occur, may increase the rate by 50 mL/hour every hour (maximum rate: 200 mL/hour).
Week 2 infusion (500 mL volume; 16 mg/kg): Use a dilution volume of 500 mL only if there were no infusion reactions during the previous week's infusion. Otherwise, continue to use a dilution volume of 1,000 mL. Infuse at 50 mL/hour for the first hour. If no infusion reactions occur, may increase the rate by 50 mL/hour every hour (maximum rate: 200 mL/hour).
Subsequent infusions (500 mL volume; 16 mg/kg): Use a modified initial rate for subsequent infusions (week 3 onwards) only if there were no infusion reactions during the previous infusion. Otherwise, continue to use instructions for the week 2 infusion. Infuse at 100 mL/hour for the first hour. If no infusion reactions occur, may increase the rate by 50 mL/hour every hour (maximum rate: 200 mL/hour).
Accelerated infusion rate (off-label) (Ref): An accelerated infusion rate was studied (small, single-center study) in patients with multiple myeloma who have received ≥2 daratumumab doses at the standard infusion rate. Twenty percent of the dose was infused over 30 minutes (200 mL/hour) and the remaining 80% of the dose was then infused over 60 minutes (450 mL/hour), delivering the dose over a total of ~90 minutes. Standard existing premedications were continued (montelukast and famotidine were included in the premedication regimen), but may be tapered over subsequent infusions if tolerated (refer to protocol for details). Vital signs were monitored prior to infusion, every 15 minutes for the first hour, and then at the end of infusion; patients were observed for signs/symptoms of infusion reaction for 30 minutes after the initial accelerated infusion was completed. Prior to implementing the accelerated infusion rate, patients should demonstrate tolerability to a 500 mL infusion.
Multiple myeloma (newly diagnosed):
Treatment of newly diagnosed multiple myeloma (in combination with bortezomib, thalidomide, and dexamethasone) in adults who are eligible for autologous stem cell transplant.
Treatment of newly diagnosed multiple myeloma (in combination with bortezomib, melphalan, and prednisone) in adults who are ineligible for autologous stem cell transplant.
Treatment of newly diagnosed multiple myeloma (in combination with lenalidomide and dexamethasone) in adults who are ineligible for autologous stem cell transplant.
Multiple myeloma (relapsed/refractory):
Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone and lenalidomide) in adults who have received at least 1 prior therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone and bortezomib) in adults who have received at least 1 prior therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone and carfilzomib) in patients who have received 1 to 3 prior therapies.
Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone and pomalidomide) in adults who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor.
Treatment of relapsed or refractory multiple myeloma (as monotherapy) in adults who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.
Systemic light chain amyloidosis (relapsed)
Daratumumab may be confused with daclizumab, daratumumab/hyaluronidase, darolutamide, denosumab, dinutuximab, dostarlimab, dupilimumab, durvalumab, elotuzumab, isatuximab.
Darzalex may be confused with Darzalex Faspro.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who could become pregnant should use effective contraception during therapy and for 3 months after the last daratumumab dose.
Daratumumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Based on the mechanism of action, daratumumab may cause myeloid or lymphoid cell depletion and decreased bone density in the fetus. The administration of live vaccines should be deferred for neonates and infants exposed to daratumumab in utero until a hematology evaluation can be completed. When using in combination regimens, also refer to individual monographs for additional information.
It is not known if daratumumab is present in breast milk.
Daratumumab is a monoclonal antibody; monoclonal antibodies can be detected in breast milk and are not expected to enter the neonatal or infant circulation in substantial amounts. When using in combination regimens, also refer to individual monographs for additional information.
CBCs periodically; type and screen (blood type) prior to initiating therapy. Monitor for signs/symptoms of hepatitis B virus (HBV) reactivation, infection, ocular adverse reactions, and bleeding. If ocular reactions occur, obtain an ophthalmologic exam prior to restarting daratumumab.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Accelerated infusion rate (off-label): Monitor vital signs prior to infusion, every 15 minutes for the first hour, and then at the end of infusion; patients were observed for signs/symptoms of infusion reaction for 30 minutes after the initial accelerated infusion was completed (Barr 2018).
Daratumumab is an IgG1κ human monoclonal antibody directed against CD38. CD38 is a cell surface glycoprotein which is highly expressed on myeloma cells, yet is expressed at low levels on normal lymphoid and myeloid cells (Lokhorst 2015). By binding to CD38, daratumumab inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell mediated cytotoxicity, and antibody dependent cellular phagocytosis.
Distribution: Central: Monotherapy: 4.7 ± 1.3 L; Combination therapy: 4.4 ± 1.5 L
Half-life elimination: 18 ± 9 days
Excretion: Clearance: 171.4 ± 95.3 mL/day
Body weight: Central volume of distribution and clearance increase with increasing body weight.
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