Daratumumab And Hyaluronidase-Fihj (Human Recombinant)
FDA Drug Information • Also known as: Darzalex Faspro
- Brand Names
- Darzalex Faspro
- Drug Class
- CD38-directed Cytolytic Antibody [EPC], Endoglycosidase [EPC]
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Daratumumab is an immunoglobulin G1 kappa (IgG1κ) human monoclonal antibody that binds to the CD38 antigen. Daratumumab is produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. The molecular weight of daratumumab is approximately 148 kDa. Hyaluronidase (recombinant human) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by Chinese Hamster Ovary cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (recombinant human) has a molecular weight of approximately 61 kDa. DARZALEX FASPRO ® (daratumumab and hyaluronidase-fihj) injection is a sterile, preservative-free, colorless to yellow, and clear to opalescent solution supplied in a single-dose vial for subcutaneous administration. Each DARZALEX FASPRO 15 mL single-dose vial contains 1,800 mg of daratumumab and 30,000 units of hyaluronidase, L-histidine (4.9 mg), L-histidine hydrochloride monohydrate (18.4 mg), L-methionine (13.5 mg), polysorbate 20 (6 mg), sorbitol (735.1 mg), and Water for Injection, USP.
What Is Daratumumab And Hyaluronidase-Fihj (Human Recombinant) Used For?
1 INDICATIONS AND USAGE DARZALEX FASPRO is a combination of daratumumab, a CD38-directed cytolytic antibody, and hyaluronidase, an endoglycosidase, indicated for the treatment of adult patients with: multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant multiple myeloma in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant multiple myeloma in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy multiple myeloma in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy multiple myeloma in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor multiple myeloma in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy multiple myeloma as monotherapy, in patients who have received at least three 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 high-risk smoldering multiple myeloma as monotherapy light chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone in newly diagnosed patients. Limitations of Use: DARZALEX FASPRO is not indicated and is not recommended for the treatment of 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 ( 1.3 ) 1.1 Multiple Myeloma DARZALEX FASPRO is indicated for the treatment of adult patients with [see Clinical Studies (14) ] : multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant. multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant. multiple myeloma in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant. multiple myeloma in combination with lenalidomide and dexamethasone in...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For subcutaneous use only. Pre-medicate with a corticosteroid, acetaminophen and a histamine-1 receptor antagonist. ( 2.6 ) The recommended dosage of DARZALEX FASPRO is (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to recommended schedule. ( 2.2 , 2.3 , 2.4 ) Administer post-medications as recommended. ( 2.6 ) 2.1 Important Dosing Information DARZALEX FASPRO is for subcutaneous use only. Administer medications before and after administration of DARZALEX FASPRO to minimize administration-related reactions [see Dosage and Administration (2.6) ] . Type and screen patients prior to starting DARZALEX FASPRO. 2.2 Recommended Dosage for Multiple Myeloma The recommended dose of DARZALEX FASPRO is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3 to 5 minutes. Tables 1, 2, 3, 4, 5, and 6 provide the recommended dosing schedule when DARZALEX FASPRO is administered as monotherapy or as part of a combination therapy. Monotherapy and In Combination with Lenalidomide and Dexamethasone (DARZALEX FASPRO-Rd), Pomalidomide and Dexamethasone (DARZALEX FASPRO-Pd) or Carfilzomib and Dexamethasone (DARZALEX FASPRO-Kd) Use the dosing schedule provided in Table 1 when DARZALEX FASPRO is administered: in combination with lenalidomide and dexamethasone (4-week cycle) OR in combination with pomalidomide and dexamethasone (4-week cycle) OR in combination with carfilzomib and dexamethasone (4-week cycle) OR as monotherapy. Table 1: DARZALEX FASPRO dosing schedule in combination with lenalidomide, pomalidomide or carfilzomib and dexamethasone (4-week cycle) and for monotherapy Weeks Schedule Weeks 1 to 8 weekly (total of 8 doses) Weeks 9 to 24 First dose of the every-2-week dosing schedule is given at Week 9 every two weeks (total of 8 doses) Week 25 onwards until disease progression First dose of the every-4-week dosing schedule is given at Week 25 every four weeks When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.2) and the prescribing information for dosage recommendations for the other drugs. In Combination with Bortezomib, Melphalan and Prednisone (DARZALEX FASPRO-VMP) Use the dosing schedule provided in Table 2 when DARZALEX FASPRO is administered in combination with bortezomib, melphalan and prednisone (6-week cycle). Table 2: DARZALEX FASPRO dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle) Weeks Schedule Weeks 1 to 6 weekly (total of 6 doses) Weeks 7 to 54 First dose of the every-3-week dosing schedule is given at Week 7 every three weeks (total of 16 doses) Week 55 onwards until disease progression First dose of the every-4-week dosing schedule is given at Week 55 every four weeks When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.1) and the...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity and Other Administration Reactions [see Warnings and Precautions (5.1) ] . Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis [see Warnings and Precautions (5.2) ] . Infections [see Warnings and Precautions (5.3) ] . Neutropenia [see Warnings and Precautions (5.4) ] . Thrombocytopenia [see Warnings and Precautions (5.5) ] . The most common adverse reactions (≥20%) in patients with multiple myeloma eligible for autologous stem cell transplant who received DARZALEX FASPRO-VRd are peripheral neuropathy, fatigue, upper respiratory infection, constipation, musculoskeletal pain, insomnia, rash, diarrhea, edema, and pyrexia. ( 6.1 ) The most common adverse reactions (≥20%) in patients with multiple myeloma who were ineligible for autologous stem cell transplant who received DARZALEX FASPRO-VRd are upper respiratory tract infection, sensory neuropathy, musculoskeletal pain, diarrhea, fatigue, edema, rash, motor dysfunction, COVID-19, constipation, sleep disorder, cough, pneumonia, renal impairment, dizziness, nausea, urinary tract infection, pyrexia, abdominal pain, dyspnea, decreased appetite, and bruising. ( 6.1 ) The most common adverse reaction (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO monotherapy is upper respiratory tract infection. ( 6.1 ) The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-VMP are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. ( 6.1 ) The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Rd are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea. ( 6.1 ) The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Pd are fatigue, pneumonia, upper respiratory tract infection, and diarrhea. ( 6.1 ) The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Kd are upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral. ( 6.1 ) The most common adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX FASPRO monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions. ( 6.1 ) The most common adverse reactions (≥20%) in patients with light chain (AL) amyloidosis are upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough. ( 6.1 ) The most common (≥40%) hematology laboratory abnormalities with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Newly Diagnosed Multiple Myeloma Eligible for Autologous Stem Cell Transplant In Combination with Bortezomib, Lenalidomide and Dexamethasone The safety of DARZALEX FASPRO in combination with bortezomib, lenalidomide and dexamethasone (n=351) from the start of induction to the end of consolidation compared to bortezomib, lenalidomide and dexamethasone (VRd) (n=347) was evaluated in PERSEUS [see...
Drug Interactions
7 DRUG INTERACTIONS 7.1 Effects of Daratumumab on Laboratory Tests Interference with Indirect Antiglobulin Tests (Indirect Coombs Test) Daratumumab binds to CD38 on RBCs and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding [see References (15) ] or genotyping. Since the Kell blood group system is also sensitive to DTT treatment, supply K-negative units after ruling out or identifying alloantibodies using DTT-treated RBCs. If an emergency transfusion is required, administer non-cross-matched ABO/RhD-compatible RBCs per local blood bank practices. Interference with Serum Protein Electrophoresis and Immunofixation Tests Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). False positive SPE and IFE assay results may occur for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In DARZALEX FASPRO-treated patients with persistent very good partial response, where daratumumab interference is suspected, consider using a FDA-approved daratumumab-specific IFE assay to distinguish daratumumab from any remaining endogenous M protein in the patient's serum, to facilitate determination of a complete response.
Contraindications
4 CONTRAINDICATIONS DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase or any of the components of the formulation [see Warnings and Precautions (5.1) and Adverse Reactions (6.2) ]. Patients with a history of severe hypersensitivity to daratumumab, hyaluronidase or any of the components of the formulation. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. The assessment of associated risks with daratumumab products is based on the mechanism of action and data from target antigen CD38 knockout animal models (see Data ) . There are no available data on the use of DARZALEX FASPRO in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The combination of DARZALEX FASPRO and lenalidomide, thalidomide or pomalidomide is contraindicated in pregnant women, because lenalidomide, thalidomide and pomalidomide may cause birth defects and death of the unborn child. Lenalidomide, thalidomide and pomalidomide are only available through a REMS program. Refer to the lenalidomide, thalidomide or pomalidomide prescribing information on use during pregnancy. Clinical Considerations Fetal/Neonatal Adverse Reactions Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action, DARZALEX FASPRO may cause depletion of fetal CD38 positive immune cells and decreased bone density. Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Data Animal Data DARZALEX FASPRO for subcutaneous injection contains daratumumab and hyaluronidase . Mice that were genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density at birth that recovered by 5 months of age. Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in the regulation of humoral immune responses (mice), feto-maternal immune tolerance (mice), and early embryonic development (frogs). No...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING DARZALEX FASPRO ® (daratumumab and hyaluronidase-fihj) injection is a sterile, preservative-free, colorless to yellow, and clear to opalescent solution for subcutaneous use supplied as individually packaged single-dose vials providing 1,800 mg of daratumumab and 30,000 units of hyaluronidase per 15 mL (NDC 57894-503-01). Store DARZALEX FASPRO vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light. Do not freeze or shake.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.