Daratumumab

FDA Drug Information • Also known as: Darzalex, Darzalex Iv

Brand Names: Darzalex, Darzalex Iv
Dosage Form: LIQUID
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Daratumumab is an immunoglobulin G1 kappa (IgG1κ) human monoclonal antibody that binds to CD38 antigen. It is produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. The molecular weight of daratumumab is approximately 148 kDa. DARZALEX ® (daratumumab) injection is supplied as a colorless to pale yellow preservative-free solution for intravenous use in a single-dose vial. The pH is 5.5. Each DARZALEX 20 mL single-dose vial contains (NDC 57894-502-20) 400 mg daratumumab, glacial acetic acid (3.7 mg), mannitol (510 mg), polysorbate 20 (8 mg), sodium acetate trihydrate (59.3 mg), sodium chloride (70.1 mg), and Water for Injection, USP. Each DARZALEX 5 mL single-dose vial contains (NDC 57894-502-05) 100 mg daratumumab, glacial acetic acid (0.9 mg), mannitol (127.5 mg), polysorbate 20 (2 mg), sodium acetate trihydrate (14.8 mg), sodium chloride (17.5 mg), and Water for Injection, USP. Each DARZALEX 20 mL single-dose vial contains (NDC 57894-505-20) 400 mg daratumumab, L-histidine (7 mg), L-histidine hydrochloride monohydrate (32.6 mg), L-methionine (20 mg), polysorbate 20 (8 mg), sorbitol (1093 mg), and Water for Injection, USP. Each DARZALEX 5 mL single-dose vial contains (NDC 57894-505-05) 100 mg daratumumab, L-histidine (1.8 mg), L-histidine hydrochloride monohydrate (8.2 mg), L-methionine (5 mg), polysorbate 20 (2 mg), sorbitol (273.3 mg), and Water for Injection, USP.

What Is Daratumumab Used For?

1 INDICATIONS AND USAGE DARZALEX is indicated for the treatment of adult patients with 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. in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant. in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant. in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy. in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. 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. DARZALEX is a CD38-directed cytolytic antibody indicated for the treatment of adult patients with 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 in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor 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. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Pre-medicate with corticosteroids, antipyretics and antihistamines. ( 2.3 ) Dilute and administer as an intravenous infusion. ( 2.5 ) Recommended dose is 16 mg/kg actual body weight. See full prescribing information for drugs used in combination and schedule. ( 2.2 ) Administer post-infusion medications. ( 2.3 ) 2.1 Important Dosing Information Administer pre-infusion and post-infusion medications [see Dosage and Administration (2.3) ] . Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.5) ]. DARZALEX should be administered by a healthcare provider, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions if they occur [see Warnings and Precautions (5.1) ]. Type and screen patients prior to starting DARZALEX [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage Monotherapy and In Combination with Lenalidomide (D-Rd) or Pomalidomide (D-Pd) and Dexamethasone The DARZALEX dosing schedule in Table 1 is for combination therapy (4-week cycle regimens) and monotherapy as follows: - combination therapy with lenalidomide and low-dose dexamethasone for newly diagnosed patients ineligible for autologous stem cell transplant (ASCT) and in patients with relapsed/refractory multiple myeloma - combination therapy with pomalidomide and low-dose dexamethasone for patients with relapsed/refractory multiple myeloma - monotherapy for patients with relapsed/refractory multiple myeloma. The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule: Table 1: DARZALEX Dosing Schedule in Combination With Lenalidomide or Pomalidomide (4-Week Cycle) and Low-Dose Dexamethasone 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 For dosing instructions of combination agents administered with DARZALEX, see Clinical Studies (14) and manufacturer's prescribing information. In Combination with Bortezomib, Melphalan and Prednisone (D-VMP) The DARZALEX dosing schedule in Table 2 is for combination therapy with bortezomib, melphalan and prednisone (6-week cycle regimen) for patients with newly diagnosed multiple myeloma ineligible for ASCT. The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an intravenous infusion according to the following dosing schedule: Table 2: DARZALEX Dosing Schedule in Combination With Bortezomib, Melphalan and Prednisone ([VMP], 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-related reactions [see Warnings and Precautions (5.1) ] . Neutropenia [see Warnings and Precautions (5.3) ] . Thrombocytopenia [see Warnings and Precautions (5.4) ] . The most frequently reported adverse reactions (incidence ≥20%) are: upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. ( 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. The safety data described below reflects exposure to DARZALEX (16 mg/kg) in 2,459 patients with multiple myeloma including 2,303 patients who received DARZALEX in combination with background regimens and 156 patients who received DARZALEX as monotherapy. In this pooled safety population, the most common adverse reactions (≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. Newly Diagnosed Multiple Myeloma Ineligible for Autologous Stem Cell Transplant Combination Treatment with Lenalidomide and Dexamethasone (DRd) The safety of DARZALEX in combination with lenalidomide and dexamethasone was evaluated in MAIA [see Clinical Studies (14.1) ]. Adverse reactions described in Table 7 reflect exposure to DARZALEX for a median treatment duration of 25.3 months (range: 0.1 to 40.44 months) for daratumumab-lenalidomide-dexamethasone (DRd) and of 21.3 months (range: 0.03 to 40.64 months) for lenalidomide-dexamethasone (Rd). Serious adverse reactions with a 2% greater incidence in the DRd arm compared to the Rd arm were pneumonia (DRd 15% vs Rd 8%), bronchitis (DRd 4% vs Rd 2%) and dehydration (DRd 2% vs Rd <1%). Table 7: Adverse Reactions Reported in ≥10% of Patients and With at Least a 5% Greater Frequency in the DRd Arm in MAIA Body System Adverse Reaction DRd (N=364) Rd (N=365) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Key: D=daratumumab, Rd=lenalidomide-dexamethasone. Gastrointestinal disorders Diarrhea 57 7 0 46 4 0 Constipation 41 1 <1 36 <1 0 Nausea 32 1 0 23 1 0 Vomiting 17 1 0 12 <1 0 Infections Upper respiratory tract infection Acute sinusitis, Bacterial rhinitis, Laryngitis, Metapneumovirus infection, Nasopharyngitis, Oropharyngeal candidiasis, Pharyngitis, Respiratory syncytial virus infection, Respiratory tract infection, Respiratory tract infection viral, Rhinitis, Rhinovirus infection, Sinusitis, Tonsillitis, Tracheitis, Upper respiratory tract infection, Viral pharyngitis, Viral rhinitis, Viral upper respiratory tract infection 52 2 <1 36 2 <1 Bronchitis Bronchiolitis, Bronchitis, Bronchitis viral, Respiratory syncytial virus bronchiolitis, Tracheobronchitis 29 3 0 21 1 0 Pneumonia Atypical pneumonia, Bronchopulmonary aspergillosis, Lung infection, Pneumocystis jirovecii infection, Pneumocystis jirovecii pneumonia, Pneumonia, Pneumonia aspiration, Pneumonia pneumococcal, Pneumonia viral, Pulmonary mycosis 26 14 1 14 7 1 Urinary tract infection 18 2 0 10 2 0 General disorders and administration site conditions Infusion-related reactions Infusion-related reaction includes terms determined by investigators to be related to infusion 41 2 <1 0 0 0 Peripheral edema Generalized edema, Gravitational edema, Edema, Peripheral edema, Peripheral swelling 41 2 0 33 1 0 Fatigue 40 8 0 28 4 0...

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 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 is contraindicated in patients with a history of severe hypersensitivity (e.g. anaphylactic reactions) to daratumumab or any of the components of the formulation [see Warnings and Precautions (5.1) ] . Patients with a history of severe hypersensitivity to daratumumab or any of the components of the formulation. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary DARZALEX 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 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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 and lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women, because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Lenalidomide, pomalidomide, and thalidomide are only available through a REMS program. Refer to the lenalidomide, pomalidomide, or thalidomide 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 may cause depletion of fetal CD38 positive immune cells and decreased bone density. Defer administering live vaccines to neonates and infants exposed to DARZALEX in utero until a hematology evaluation is completed. Data Animal Data 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 regulating humoral immune responses (mice),...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied DARZALEX ® (daratumumab) injection is a colorless to pale yellow, preservative-free solution for intravenous infusion. NDC 57894-502-05 and NDC 57894-505-05 each contain one 100 mg/5 mL (20 mg/mL) single-dose vial NDC 57894-502-20 and NDC 57894-505-20 each contain one 400 mg/20 mL (20 mg/mL) single-dose vial Storage and Stability Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. This product contains no preservative.

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.