Version May 2024
Note: Premedicate 1 to 3 hours prior to each infusion with a corticosteroid, an oral antipyretic, and an oral or IV antihistamine; postdosing, administer an oral corticosteroid (based on regimen and/or medical history) to reduce the risk of delayed infusion reactions (see “Premedication” and “Post-dose Medication” below). To prevent herpes zoster reactivation, initiate antiviral prophylaxis within 1 week after starting daratumumab/hyaluronidase and continue for 3 months following completion of treatment. Refer to Dexamethasone, Lenalidomide, Thalidomide, Pomalidomide, Bortezomib, Carfilzomib, Cyclophosphamide, Melphalan, and/or Prednisone monographs for dosing when used as a part of daratumumab-based combination therapy.
Do NOT substitute daratumumab/hyaluronidase (for subcutaneous use) with daratumumab (IV); products have different dosing and are NOT interchangeable.
Light chain amyloidosis, newly diagnosed:
In combination with bortezomib, cyclophosphamide and dexamethasone (Dh-VCd):
Weeks 1 to 8: SUBQ: Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity or a maximum of 2 years.
Multiple myeloma, newly diagnosed:
In combination with bortezomib, thalidomide, and dexamethasone (Dh-VTd); in patients eligible for autologous stem cell transplant:
Induction:
Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 16: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 4 doses.
Consolidation (following autologous stem cell transplant): Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks for a total of 4 doses.
In combination with lenalidomide and dexamethasone (Dh-Rd); in patients ineligible for autologous stem cell transplant:
Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
In combination with bortezomib, melphalan, and prednisone (Dh-VMP); in patients ineligible for autologous stem cell transplant (Ref):
Weeks 1 to 6: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 6 doses.
Weeks 7 to 54: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 3 weeks (beginning week 7) for a total of 16 doses.
Weeks 55 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 55) until disease progression or unacceptable toxicity.
Multiple myeloma, relapsed/refractory:
As monotherapy; in patients who have received at least 3 prior lines of therapy (Ref):
Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
In combination with lenalidomide and dexamethasone (Dh-Rd); in patients who have received at least 1 prior therapy (Ref):
Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
In combination with carfilzomib and dexamethasone (Dh-Kd); in patients who have received 1 to 3 prior lines of therapy (Ref):
Weeks 1 to 8: SUBQ: Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ: Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ: Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
In combination with pomalidomide and dexamethasone (Dh-Pd); in patients who have received at least 1 prior therapy, including lenalidomide and a proteosome inhibitor (Ref):
Weeks 1 to 8: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 8 doses.
Weeks 9 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 2 weeks (beginning week 9) for a total of 8 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
In combination with bortezomib and dexamethasone (Dh-Vd); in patients who have received at least 1 prior therapy:
Weeks 1 to 9: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once weekly for a total of 9 doses.
Weeks 10 to 24: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 3 weeks (beginning week 10) for a total of 5 doses.
Weeks 25 and beyond: SUBQ : Daratumumab 1,800 mg/hyaluronidase 30,000 units once every 4 weeks (beginning week 25) until disease progression or unacceptable toxicity.
Missed doses: If a daratumumab/hyaluronidase dose is missed, administer the dose as soon as possible and adjust the dosing schedule to maintain the dosing interval.
Premedication: Administer a corticosteroid, an antipyretic, and an antihistamine 1 to 3 hours prior to each daratumumab/hyaluronidase dose.
Corticosteroid:
Monotherapy: IV or Oral: Methylprednisolone (or equivalent) 100 mg; consider reducing the dose to 60 mg following the second daratumumab/hyaluronidase dose.
Combination therapy: IV or Oral: Dexamethasone 20 mg (or equivalent) prior to each daratumumab/hyaluronidase dose. If dexamethasone is the background regimen-specific corticosteroid, the dexamethasone treatment dose will serve as the corticosteroid premedication on daratumumab/hyaluronidase administration days. Do not administer background regimen-specific corticosteroids (eg, prednisone) on daratumumab/hyaluronidase days when patients receive dexamethasone (or equivalent) as a premedication.
Antipyretic: Oral: Acetaminophen 650 to 1,000 mg.
Antihistamine: IV or Oral: Diphenhydramine 25 to 50 mg or equivalent.
Note: In a clinical study, an optional leukotriene inhibitor (eg, montelukast 10 mg orally) was administered on day 1 of cycle 1 (Ref).
Postdose medication:
Monotherapy: Oral: Methylprednisolone 20 mg (or equivalent dose of an intermediate or long acting corticosteroid) for 2 days starting the day after the daratumumab/hyaluronidase dose.
Combination therapy: Consider administering oral methylprednisolone ≤20 mg (or equivalent) beginning the day after the daratumumab/hyaluronidase dose. If dexamethasone or prednisone is administered the day after the daratumumab/hyaluronidase dose as part of background combination chemotherapy regimen, additional postdose corticosteroid therapy may not be necessary.
If the patient does not experience a major systemic administration-related reaction after the first 3 daratumumab/hyaluronidase doses, consider discontinuing the administration of corticosteroids (excluding any background regimen-specific corticosteroid).
In patients with a history of chronic obstructive pulmonary disease, also consider short- and long-acting bronchodilators and inhaled corticosteroids. If no major systemic administration-related reaction occurs following the first 4 daratumumab/hyaluronidase doses, consider discontinuing these additional inhaled post medications.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 15 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, CrCl between 15 to 89 mL/minute did not have any meaningful effect on daratumumab/hyaluronidase pharmacokinetics.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (total bilirubin 1 to 1.5 times ULN and AST > ULN): There are no dosage adjustments provided in the manufacturer's labeling; however, mild impairment did not have any meaningful effect on daratumumab pharmacokinetics.
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Note: Refer to specific protocol or to Dexamethasone, Prednisone, Lenalidomide, Thalidomide, Pomalidomide, Bortezomib, Carfilzomib, Cyclophosphamide, or Melphalan monographs for dosing adjustment for toxicity when used in combination with daratumumab-based therapy.
Hematologic toxicity: No dose reductions of daratumumab/hyaluronidase are recommended; If myelosuppression occurs, consider withholding daratumumab/hyaluronidase dose to allow recovery of blood cell counts.
Nonhematologic toxicity:
Hypersensitivity: Immediately and permanently discontinue daratumumab/hyaluronidase for anaphylactic reaction or life-threatening (grade 4) administration-related reactions.
Local reactions: Consider managing symptomatically.
Ocular reactions (eg, acute myopia, anterior chamber angle narrowing, ciliochoroidal effusions): Interrupt daratumumab/hyaluronidase therapy; 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 adults. Also see individual agents.
>10%:
Gastrointestinal: Diarrhea (15%; grade 3: 1%)
Hematologic & oncologic: Decreased hemoglobin (42%; grades 3/4: 14%), decreased neutrophils (55%; grades 3/4: 19%), decreased platelet count (43%; grades 3/4: 16%), leukopenia (65%; grades 3/4: 19%), lymphocytopenia (59%; grades 3/4: 36%)
Nervous system: Fatigue (15%)
Respiratory: Upper respiratory tract infection (24%)
Miscellaneous: Fever (13%), infusion related reaction (13%)
1% to 10%:
Cardiovascular: Atrial fibrillation (<10%), hypertension (<10%), hypotension (<10%), peripheral edema (<10%)
Dermatologic: Pruritus (<10%), skin rash (<10%)
Endocrine & metabolic: Dehydration (<10%), hyperglycemia (<10%), hypocalcemia (<10%)
Gastrointestinal: Abdominal pain (<10%), constipation (<10%), decreased appetite (<10%), nausea (8%; grade 3: <1%), vomiting (<10%)
Genitourinary: Urinary tract infection (<10%)
Immunologic: Antibody development (≤7%)
Infection: Herpes zoster infection (<10%), influenza (<10%), reactivation of HBV (<10%), sepsis (<10%)
Local: Erythema at injection site (>1%), injection site reaction (<10%)
Nervous system: Chills (6%), dizziness (<10%), insomnia (<10%), paresthesia (<10%), peripheral sensory neuropathy (<10%)
Neuromuscular & skeletal: Arthralgia (<10%), back pain (10%), muscle spasm (<10%), musculoskeletal chest pain (<10%)
Respiratory: Bronchitis (<10%), cough (9%), dyspnea (6%), pneumonia (8%), pulmonary edema (<10%)
Frequency not defined:
Hematologic & oncologic: Positive indirect Coombs test
Hypersensitivity: Anaphylaxis, hypersensitivity reaction (including severe hypersensitivity reactions)
Ophthalmic: Acute angle-closure glaucoma, choroidal effusion (ciliochoroidal), myopia (acute)
History of severe hypersensitivity to daratumumab, hyaluronidase, or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Daratumumab-based therapy may increase background therapy-induced neutropenia and thrombocytopenia. Higher rates of grade 3 or 4 neutropenia have been observed in patients with lower body weights.
• Cardiac toxicity: Serious or fatal cardiac adverse reactions have been reported when administered in combination with bortezomib, cyclophosphamide, and dexamethasone for the treatment of light chain amyloidosis. Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at an increased risk for cardiac effects; patients with NYHA Class IIIB or IV disease were not included in clinical trials.
• Hepatitis B virus reactivation: Daratumumab-based therapy may be associated with hepatitis B virus (HBV) reactivation.
• Hypersensitivity: Systemic administration-related reactions (including severe or life-threatening reactions) may occur with daratumumab/hyaluronidase. In a large, pooled safety population of patients who received daratumumab/hyaluronidase as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction; grade 2 and 3 events were observed. Systemic reactions occurred more commonly with the first injection; a small number of patients experienced a systemic reaction with the second and subsequent injections. The median time to onset was ~3 hours (range: 4 minutes to 3.5 days), although most systemic administration-related reactions occurred on the day of daratumumab/hyaluronidase administration. Delayed (occurring the day after daratumumab/hyaluronidase administration) systemic administration-related reactions have occurred rarely. Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular reactions (eg, choroidal effusion, acute myopia, acute angle closure glaucoma); other signs/symptoms of systemic reactions may include respiratory symptoms (eg, bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, wheezing), as well as anaphylactic reaction, pruritus, fever, chills, nausea, vomiting, chest pain, hypotension, and blurred vision.
• Local reactions: Local injection-site reactions have occurred with daratumumab/hyaluronidase, including rare grade 2 events. The most frequent local reaction was injection-site erythema. Local reactions occurred a median of ~5 minutes (range: up to ~7 days) after starting daratumumab/hyaluronidase administration.
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-based therapy 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 upper respiratory tract infection, urinary tract infection, dizziness, cough, dyspnea, diarrhea, nausea, fatigue, peripheral edema, weakness, hypotension, and pneumonia (compared to patients <65 years of age).
Other warnings/precautions:
• Do not interchange: Daratumumab/hyaluronidase (for subcutaneous administration) and daratumumab (for IV administration) have different dosing and are NOT interchangeable.
• Interference with serological testing: Through binding to CD38 on red blood cells, daratumumab-based therapy 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 dose. In addition, daratumumab (bound to red blood cells) 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/hyaluronidase. Type and screen patients prior to treatment initiation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Darzalex Faspro: Daratumumab 1,800 mg and hyaluronidase-fihj 30,000 units per 15 mL (15 mL)
No
Solution (Darzalex Faspro Subcutaneous)
1800-30000MG-UT/15ML (per mL): $729.49
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, Subcutaneous:
Darzalex SC: 1800 mg/15 mL (15 mL)
Note: Check label to ensure appropriate product is administered; daratumumab/hyaluronidase (subcutaneous) and daratumumab (IV) are different products and are NOT interchangeable. The volume of the dose of daratumumab 1,800 mg/hyaluronidase 30,000 units is 15 mL.
SUBQ: Allow refrigerated product to reach room temperature prior to administration. Administer into the subcutaneous tissue of the abdomen ~3 inches (7.5 cm) to the right or left of the navel over ~3 to 5 minutes. Daratumumab/hyaluronidase should be administered by a health care provider. Rotate injection sites for successive injections. Do not administer into areas where the skin is red, bruised, tender, hard, or areas where there are scars. Pause or slow down subcutaneous delivery rate if the patient experiences pain. If pain is not alleviated by pausing or slowing down delivery rate, select a second injection site on the opposite side of the abdomen to deliver the remainder of the dose.
Daratumumab/hyaluronidase is compatible with polypropylene, polyethylene, or PVC subcutaneous infusion sets, and with stainless steel transfer and injection needles. Do not administer other subcutaneous medications at the same site as daratumumab/hyaluronidase.
Light chain amyloidosis (newly diagnosed): Treatment of newly diagnosed light chain amyloidosis (in combination with bortezomib, cyclophosphamide, and dexamethasone) in adults.
Limitations of use: Daratumumab/hyaluronidase is not indicated nor recommended for the treatment of light chain amyloidosis in patients who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.
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 lenalidomide and dexamethasone) in adults who have received at least 1 prior therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with bortezomib and dexamethasone) in adults who have received at least 1 prior therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with carfilzomib and dexamethasone) in adults who have received 1 to 3 prior lines of therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with pomalidomide and dexamethasone) in adults who have received at least 1 prior line of therapy, including lenalidomide and a proteosome inhibitor.
Treatment of relapsed or refractory multiple myeloma (as monotherapy) in adults who have received at least 3 prior lines of therapy, which included a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab/hyaluronidase may be confused with daclizumab, daratumumab, darolutamide, denosumab, dinutuximab, dostarlimab, dupilimumab, durvalumab, elotuzumab, isatuximab, pertuzumab/trastuzumab/hyaluronidase, rituximab/hyaluronidase, trastuzumab/hyaluronidase.
Darzalex Faspro may be confused with Darzalex.
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
Alpha-/Beta-Agonists: Hyaluronidase may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider therapy modification
Antihistamines: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
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
Corticosteroids (Systemic): May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. 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
Estrogen Derivatives: May diminish the therapeutic effect of Hyaluronidase. 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
Local Anesthetics: Hyaluronidase may enhance the adverse/toxic effect of Local Anesthetics. Risk C: Monitor therapy
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
Phenylephrine (Systemic): Hyaluronidase may enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider therapy modification
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
Salicylates: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
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
Evaluate pregnancy status prior to use in patients who may become pregnant.
Daratumumab/hyaluronidase may be used as monotherapy or in combination with other anticancer agents. When used as monotherapy, patients who may become pregnant should use effective contraception during therapy and for 3 months after the last daratumumab/hyaluronidase dose. If daratumumab/hyaluronidase is used in combination regimens (eg, lenalidomide, thalidomide, pomalidomide), pregnancy testing and contraception requirements for those agents should also be followed.
Refer to the Daratumumab, Hyaluronidase, and other individual monographs (when using combination regimens) for additional information.
Based on the mechanism of action, in utero exposure to daratumumab/hyaluronidase may cause fetal harm.
Daratumumab/hyaluronidase may be used as monotherapy or in combination with other anticancer agents. Daratumumab/hyaluronidase is contraindicated for use in pregnancy when used in combination with some anticancer agents (eg, lenalidomide, thalidomide, pomalidomide).
Refer to the Daratumumab, Hyaluronidase, and other individual monographs (when using combination regimens) for additional information.
It is not known if daratumumab/hyaluronidase is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during maternal treatment with daratumumab/hyaluronidase. Daratumumab/hyaluronidase may be used as monotherapy or in combination with other anticancer agents; refer to the Daratumumab, Hyaluronidase, and other individual monographs (when using combination regimens) for additional information.
Blood type (type and screen prior to initiating therapy). CBC periodically. Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor for signs/symptoms of hypersensitivity (systemic and local reactions). Monitor for cardiac toxicity; in patients with cardiac involvement of light chain amyloidosis, monitor more frequently for cardiac adverse reactions. Monitor for signs/symptoms of HBV reactivation, infection, ocular adverse reactions, and bleeding.
The American Society of Clinical Oncology hepatitis B virus (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.
Daratumumab is an IgG1κ human monoclonal antibody directed against CD38. CD38 is a cell surface glycoprotein which is highly expressed on myeloma cells. 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. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. At the recommended dose, hyaluronidase acts locally and the effects are reversible; permeability of subcutaneous tissue is restored within 24 to 48 hours.
Distribution: Vd: SUBQ: Multiple myeloma: Central compartment: 5.2 L; peripheral compartment: 3.8 L; Light chain amyloidosis: 10.8 L.
Bioavailability: SUBQ: 69%.
Half-life elimination: SUBQ: 20 days (multiple myeloma); 28 days (light chain amyloidosis).
Time to peak: SUBQ: ~3 days (multiple myeloma); ~4 days (light chain amyloidosis).
Excretion: Clearance: 119 mL/day (multiple myeloma); 210 mL/day (light chain amyloidosis).
Body weight: After administration of daratumumab 1,800 mg/hyaluronidase 30,000 units (monotherapy) for multiple myeloma, the mean maximum Ctrough after the eighth dose was 12% lower in the higher body weight (BW) group (>85 kg) while the mean maximum Ctrough was 81% higher in the lower BW group (≤50 kg), when compared to the corresponding BW groups receiving daratumumab IV. When administered for light chain amyloidosis, the mean maximum Ctrough after the eighth dose was 22% lower in the higher BW group (>85 kg) and 37% higher in the lower BW group (≤50 kg) as compared to patients with body weight of 51 to 85 kg.
Race/ethnicity: After administration of daratumumab 1,800 mg/hyaluronidase 30,000 units in patients with light chain amyloidosis, the mean maximum daratumumab Ctrough after the eighth dose was 24% higher in Black patients compared to White patients; Asian patients had 16% higher mean maximum Ctrough after the eighth dose compared to White patients.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
