DARZALEX Daratumumab 100 mg/5mL Injection, Solution, Concentrate
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
Daratumumab injection is used alone or in combination with other medications to treat multiple myeloma (a type of cancer of the bone marrow) in newly diagnosed people and in people who have not improved with treatment or who have improved after treatment with other medications but the condition returned. Daratumumab is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells.
Read the full MedlinePlus article ↗- Darzalex is a type of targeted therapy called a monoclonal antibody. It works by homing in on a protein called CD38 that sits on the surface of myeloma cells. Once it locks on, it...
- What exactly is Darzalex and what is it supposed to do for my myeloma?
- No, Darzalex can't be taken at home. It's given as an IV infusion through a vein, always in a clinic or infusion center by trained healthcare staff. That's because there's a risk o...
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UNII Q40Q9N063P
Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
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A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
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Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
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Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Darzalex IV 100 mg/5mL 57894-0505-05 | Janssen | 1 vial | — | — | FDA listed | — |
| Darzalex 100 mg/5mLthis 57894-0502-05 | Janssen | 1 vial | — | — | Discontinued | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
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- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Nov 16, 2027 |
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 57894-0502-05 You're viewing this | 1 VIAL in 1 CARTON (57894-502-05) / 5 mL in 1 VIAL | 2015-11-16 | Discontinued by firm |
| 57894-0502-20 | 1 VIAL in 1 CARTON (57894-502-20) / 20 mL in 1 VIAL | 2015-11-16 | Discontinued by firm |
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 )
2.1Important 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) ] .
2.2Recommended 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 onwards until disease progression First dose of the every-4-week dosing schedule is given at Week 55 every four weeks For dosing instructions of combination agents administered with DARZALEX see Clinical Studies (14.1) .
In Combination with Bortezomib, Thalidomide and Dexamethasone (D-VTd) The DARZALEX dosing schedule in Table 3 is for combination therapy with bortezomib, thalidomide, and dexamethasone (4-week cycle regimen) for patients with newly diagnosed multiple myeloma eligible 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 3: DARZALEX Dosing Schedule in Combination With Bortezomib, Thalidomide and Dexamethasone ([VTd]; 4-Week Cycle) Treatment phase Weeks Schedule Induction Weeks 1 to 8 weekly (total of 8 doses) Weeks 9 to 16 First dose of the every-2-week dosing schedule is given at Week 9 every two weeks (total of 4 doses) Stop for high dose chemotherapy and ASCT…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS DARZALEX is a colorless to pale yellow, preservative-free solution available as: Injection: 100 mg/5 mL (20 mg/mL) in a single-dose vial. 400 mg/20 mL (20 mg/mL) in a single-dose vial. Injection : 100 mg/5 mL (20 mg/mL) solution in a single-dose vial ( 3 ) 400 mg/20 mL (20 mg/mL) solution in a single-dose vial ( 3 )
⛔ 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Infusion-related reactions : Interrupt DARZALEX infusion for infusion-related reactions of any severity. Permanently discontinue the infusion in case of anaphylactic reactions or life-threatening infusion-related reactions and institute appropriate emergency care. ( 2.4 , 5.1 ) Interference with cross-matching and red blood cell antibody screening : Type and screen patients prior to starting treatment.
Inform blood banks that a patient has received DARZALEX. ( 5.2 , 7.1 ) Infections : DARZALEX can cause serious and fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately.
( 5.3 ) Neutropenia : Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Dose delay may be required to allow recovery of neutrophils.
( 5.4 ) Thrombocytopenia : Monitor complete blood cell counts periodically during treatment. Dose delay may be required to allow recovery of platelets. ( 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm.
Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception. ( 5.7 , 8.1 , 8.3 )
5.1Infusion-Related Reactions DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening and fatal outcomes have been reported [see Adverse Reactions (6.2) ] . In clinical trials (monotherapy and combination: N=2,066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions.
Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). The incidence of infusion modification due to reactions was 36%.
Median durations of 16 mg/kg infusions for the Week 1, Week 2, and subsequent infusions were approximately 7, 4, and 3 hours respectively. Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Prior to the introduction of post-infusion medication in clinical trials, infusion-related reactions occurred up to 48 hours after infusion.
Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision [see Adverse Reactions (6.1) ] .
When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion rate/dilution volume used upon re-initiation was that used for the last DARZALEX infusion prior to interruption for ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions.
In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days i.e. 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
The median time to onset of a reaction was 1.8 hours (range: 0.1 to 5.4 hours). The incidence of infusion interruptions due to reactions was 30%. Median durations of i…
🤒 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) ] . Infections [see Warnings and Precautions (5.3) ] . Neutropenia [see Warnings and Precautions (5.4) ] .
Thrombocytopenia [see Warnings and Precautions (5.5) ] . 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 .
6.1Clinical 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…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Effects 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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), feto-maternal immune tolerance (mice), and early embryonic development (frogs).
8.2Lactation Risk Summary There is no data on the presence of daratumumab in human milk, the effects on the breastfed child, or the effects on milk production. Maternal immunoglobulin G is known to be present in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts.
Because of the potential for serious adverse reactions in the breastfed child when DARZALEX is administered with lenalidomide, pomalidomide, or thalidomide, advise women not to breastfeed during treatment with DARZALEX. Refer to lenalidomide, pomalidomide, or thalidomide prescribing information for additional information.
8.3Females and Males of Reproductive Potential DARZALEX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing With the combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide, refer to the lenalidomide, pomalidomide, or thalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential. Contraception Advise females of reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.
Additionally, refer to the lenalidomide, pomalidomide, or thalidomide labeling for additional recommendations for contraception.
8.4Pediatric Use Safety and effectiveness of DARZALEX in pediatric patients have not been established. The safety and effectiveness of DARZALEX in combination with chemotherapy were assessed but not established in a single open-label trial (DELPHINUS; NCT03384654) in 34 pediatric patients (2 to <17 years of age) with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. No new safety signals were observed in these pediatric patients.
The pharmacokinetic parameters in these pedia…
🤰 Pregnancy ▾
8.1Pregnancy 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), feto-maternal immune tolerance (mice), and early embryonic development (frogs).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of DARZALEX in pediatric patients have not been established. The safety and effectiveness of DARZALEX in combination with chemotherapy were assessed but not established in a single open-label trial (DELPHINUS; NCT03384654) in 34 pediatric patients (2 to <17 years of age) with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. No new safety signals were observed in these pediatric patients.
The pharmacokinetic parameters in these pediatric patients were within range of values previously observed in adults with multiple myeloma given the same dose based on body weight.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 2,459 patients who received DARZALEX at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age and older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older than in younger patients [see Adverse Reactions (6.1) ] .
Among patients with relapsed and refractory multiple myeloma (n=1,213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Within the DKd group in CANDOR, fatal adverse reactions occurred in 14% of patients 65 years and older compared to 6% of patients less than 65 years. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues and has multiple functions, such as receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and 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 (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP).
A subset of myeloid derived suppressor cells (CD38+MDSCs), regulatory T cells (CD38+T regs ) and B cells (CD38+B regs ) are decreased by daratumumab.
12.2Pharmacodynamics NK cells express CD38 and are susceptible to daratumumab mediated cell lysis. Decreases in absolute counts and percentages of total NK cells (CD16+CD56+) and activated (CD16+CD56 dim ) NK cells in peripheral whole blood and bone marrow were observed with DARZALEX treatment. Exposure-Response Relationship The exposure-response relationship and time course of pharmacodynamics of DARZALEX have not been fully characterized.
Cardiac Electrophysiology DARZALEX as a large protein has a low likelihood of direct ion channel interactions. There is no evidence from non-clinical or clinical data to suggest that DARZALEX has the potential to delay ventricular repolarization.
12.3Pharmacokinetics Daratumumab area under the concentration-time curve (AUC) increases more than proportionally over a dosage range from 1 to 24 mg/kg (0.06 to 1.5 times the approved recommended dosage) as monotherapy or 1 to 16 mg/kg (0.06 to 1 time the approved recommended dosage) as combination therapy. Following administration of the approved recommended dosage of DARZALEX as monotherapy or in combination therapy, the mean serum maximal concentration (C max ) was approximately 2.7 to 3-fold higher at the end of weekly dosing compared to the first dose.
The mean ± standard deviation (SD) trough serum concentration (C min ) at the end of weekly dosing was 573 ± 332 µg/mL when DARZALEX was administered as monotherapy and 502 ± 196 to 607 ± 231 µg/mL when DARZALEX was administered as combination therapy. Split dosing of the first dose resulted in a different PK profile in the first day compared to single dosing; however, similar C max and C min concentrations were both predicted and observed following the administration of the second split dose on Week 1 Day 2. When DARZALEX was administered as monotherapy, daratumumab steady state was achieved approximately 5 months into the every 4-week dosing period (by the 21 st infusion).
At steady state, daratumumab mean ± SD accumulation ratio for C max was 1.6 ± 0.5. Distribution Daratumumab volume of distribution was 4.7 ±
1.3L as monotherapy and 4.4 ±
1.5L as combination therapy following administration of the approved dosage. Elimination Daratumumab clearance decreased with increasing dose and with multiple dosing. The mean ± SD linear clearance was estimated to be 171.4 ± 95.3 mL/day and the mean ± SD estimated terminal half-life associated with linear clearance was 18 ± 9 days following administration of the approved recommended dosage of DARZALEX as monotherapy.
Terminal half-life was similar when DARZALEX was administered as combination therapy. Specific Populations No clinically significant differences in the pharmacokinetics of daratumumab as monotherapy or as combination therapy were observed based on sex, age (31 to 93 years), mild [total bilirubin 1 to 1.5 times upper limit of normal (ULN) or aspartate aminotransaminase (AST)>ULN] and moderate (total bilirubin 1.5 to 3 times ULN and any AST) hepatic impairment, or renal impairment [Creatinine clearance (CLcr) 15–89 mL/min].
The effect of severe (total bilirubin >3 times ULN and a…
🧬 Mechanism of Action ▾
12.1Mechanism of Action CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues and has multiple functions, such as receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and 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 (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP).
A subset of myeloid derived suppressor cells (CD38+MDSCs), regulatory T cells (CD38+T regs ) and B cells (CD38+B regs ) are decreased by daratumumab.
📦 How Supplied / Storage and Handling ▾
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.
📦 Storage and Handling ▾
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.
📋 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.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Infusion-Related Reactions Advise patients to seek immediate medical attention for any of the following signs and symptoms of infusion-related reactions: itchy, runny or blocked nose; fever, chills, nausea, vomiting, throat irritation, cough, headache, dizziness or lightheadedness, tachycardia, chest discomfort, wheezing, shortness of breath or difficulty breathing, itching, and blurred vision [see Warnings and Precautions (5.1) ] .
Infections Inform patients about the risk of developing infections during DARZALEX treatment, and to report immediately any fever or symptoms of infection to their healthcare provider [see Warnings and Precautions (5.3) ]. Neutropenia Advise patients to contact their healthcare provider if they have a fever [see Warnings and Precautions (5.4) ] . Thrombocytopenia Advise patients to contact their healthcare provider if they notice signs of bruising or bleeding [see Warnings and Precautions (5.5) ] .
Interference with Laboratory Tests Advise patients to inform their healthcare providers, including personnel at blood transfusion centers that they are taking DARZALEX, in the event of a planned transfusion [see Warnings and Precautions (5.2) ] . Advise patients that DARZALEX can affect the results of some tests used to determine complete response in some patients and additional tests may be needed to evaluate response [see Warnings and Precautions (5.6) ] . Hepatitis B Virus (HBV) Reactivation Advise patients to inform healthcare providers if they have ever had or might have a hepatitis B infection and that DARZALEX could cause hepatitis B virus to become active again [see Adverse Reactions (6.1) ] .
Embryo-Fetal Toxicity Advise pregnant women of the potential hazard to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.7) , Use in Specific Populations (8.1 , 8.3) ] . Advise females of reproductive potential to avoid becoming pregnant during treatment with DARZALEX and for 3 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .
Advise patients that lenalidomide, pomalidomide, or thalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide, pomalidomide, and thalidomide are only available through a REMS program [see Use in Specific Populations (8.1 , 8.3) ] . Hereditary Fructose Intolerance (HFI) DARZALEX contains sorbitol.
Advise patients with HFI of the risks related to sorbitol [see Description (11) ] .