Daratumumab
Explore a selection of our essential drug information below, or:
Identification
- Summary
Daratumumab is a CD38-directed cytolytic antibody used alone or as an adjunct drug in the treatment of multiple myeloma and light chain amyloidosis.
- Brand Names
- Darzalex, Darzalex Faspro
- Generic Name
- Daratumumab
- DrugBank Accession Number
- DB09331
- Background
Daratumumab is an immunoglobulin G1 kappa monoclonal antibody developed by Janssen and Genmab.1 It was first described in the literature in 2010 as a monoclonal antibody that targets CD38+ multiple myeloma cells; the first of its kind.5
Daratumumab was granted FDA approval on 16 November 2015.6 It is approved for the treatment of multiple myeloma as monotherapy or combination therapy and light chain (AL) amyloidosis in combination with other drugs.6,7
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6466H9996N1724O2010S42
- Protein Average Weight
- 145391.67 Da
- Sequences
>Daratumumab heavy chain EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Daratumumab light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Daratumumab
- External IDs
- HuMax-CD 38
- HuMax-CD38
- JNJ-54767414
Pharmacology
- Indication
Daratumumab is indicated as an intravenous injection alone or in combination with other medications for the treatment of multiple myeloma.6 It is available as a combination product with hyaluronidase for the treatment of adults with multiple myeloma as monotherapy or combination therapy and light chain amyloidosis in combination with other drugs.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Light-chain amyloidosis Regimen in combination with: Hyaluronidase (human recombinant) (DB06205), Cyclophosphamide (DB00531), Bortezomib (DB00188), Dexamethasone (DB01234) •••••••••••• ••••• ••••• ••••••••• Used in combination to treat Multiple myeloma (mm) Combination Product in combination with: Hyaluronidase (human recombinant) (DB06205) •••••••••••• ••••• ••••••••••••••••• •• • •••••••••• ••••••••• ••• •• •••••••••••••••• ••••• Used in combination to treat Multiple myeloma (mm) Combination Product in combination with: Hyaluronidase (human recombinant) (DB06205) •••••••••••• ••••• •••••••• •••••••••• ••••••••• •••••••••• •••••••• •••••••••••••••• ••••• •••••••••• •••••••• •• ••••• ••••• ••••• ••••• •• •••••••• ••••••• Used in combination to treat Multiple myeloma (mm) Regimen in combination with: Dexamethasone (DB01234), Lenalidomide (DB00480), Hyaluronidase (human recombinant) (DB06205) •••••••••••• ••••• ••••• •••••••••• •••••••••• ••• •••••••••• •••• •••• •••••••••• Treatment of Multiple myeloma (mm) •••••••••••• ••••• ••••••••••••••••• •• • •••••••••• ••••••••• ••• •• •••••••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Daratumumab is a monoclonal antibody that targets and induces apoptosis in cells that highly express CD38, including multiple myeloma cells.6,7 It has a long duration of action as it is given every 1-4 weeks.6,7 Patients should be counselled regarding the risk of hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interferences with cross-matching and red blood cell antibody screening.6,7
- Mechanism of action
CD38 is a glycoprotein present on the surface of hematopoietic cells and is responsible for a number of cell signalling functions.1,2,3,6,7 Daratumumab is an immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets CD38.3 Cancers like multiple myeloma overexpress CD38, allowing daratumumab to have higher affinity for these cells.3 This binding allows daratumumab to induce apoptosis, antibody dependent cellular phagocytosis, and antibody and complement-dependent cytotoxicity.2,3,6,7 Antibody dependent cellular phagocytosis is mediated by the FC region of the antibody inducing phagocytes such as macrophages, antibody dependent cellular cytotoxicity is mediated by the FC region of the antibody inducing effector cells such as natural killer cells, and complement dependent cytotoxicity is mediated by the FC region of the antibody binding to and inducing complement protein activity.1,2,3
Target Actions Organism AADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 antibodyHumans - Absorption
Subcutaneous daratumumab reaches a Cmax of 592µg/mL compared to intravenous daratumumab, which reaches a Cmax of 688µg/mL.7 The AUC of subcutaneous daratumumab is 4017µg/mL*day compared to intravenous daratumumab, which has an AUC of 4019µg/mL*day.7
- Volume of distribution
Daratumumab intravenous monotherapy has a volume of distribution of 4.7 ± 1.3L and the combination therapy has a volume of distribution of 4.4 ± 1.5L.6 Subcutaneous daratumumab has a volume of distribution of the central compartment of 5.2L and a volume of distribution of the peripheral compartment of 3.8L.7
- Protein binding
Data regarding protein binding of daratumumab in serum is not readily available.6,7
- Metabolism
Monoclonal antibodies are expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.4
- Route of elimination
Monoclonal antibodies are metabolized to amino acids used for synthesis of new proteins or are eliminated by the kidneys.4
- Half-life
Intravenous daratumumab has a terminal half life of 18 ± 9 days.6 Subcutaneous daratumumab has a half life of 20 days.7
- Clearance
Intravenous daratumumab has a clearance of 171.4 ± 95.3mL/day.6 Subcutaneous daratumumab has a clearance of 119mL/day.7
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Data regarding overdoses of daratumumab are not readily available.6,7 Patients should be treated with symptomatic and supportive measures.6,7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Daratumumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Daratumumab. Aducanumab The risk or severity of adverse effects can be increased when Daratumumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Daratumumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Daratumumab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Darzalex Injection, solution, concentrate 20 mg/ml Intravenous Janssen Cilag International Nv 2020-12-16 Not applicable EU Darzalex Injection, solution, concentrate 20 mg/ml Intravenous Janssen Cilag International Nv 2016-09-08 Not applicable EU Darzalex Solution 400 mg / 20 mL Intravenous Janssen Pharmaceuticals 2016-07-12 Not applicable Canada Darzalex Injection, solution, concentrate 100 mg/5mL Intravenous Janssen Biotech, Inc. 2015-11-16 Not applicable US Darzalex Injection, solution 1800 mg Subcutaneous Janssen Cilag International Nv 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Darzalex Faspro Daratumumab (1800 mg/15mL) + Hyaluronidase (human recombinant) (30000 U/15mL) Injection Subcutaneous Janssen Biotech, Inc. 2020-05-01 Not applicable US
Categories
- ATC Codes
- L01FC01 — Daratumumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- CD38 (Clusters of Differentiation 38) inhibitors
- CD38-directed Antibody Interactions
- CD38-directed Cytolytic Antibody
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Monoclonal antibodies and antibody drug conjugates
- Narrow Therapeutic Index Drugs
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 4Z63YK6E0E
- CAS number
- 945721-28-8
References
- General References
- McKeage K: Daratumumab: First Global Approval. Drugs. 2016 Feb;76(2):275-81. doi: 10.1007/s40265-015-0536-1. [Article]
- Phipps C, Chen Y, Gopalakrishnan S, Tan D: Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. Ther Adv Hematol. 2015 Jun;6(3):120-7. doi: 10.1177/2040620715572295. [Article]
- de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, Oomen LA, Peipp M, Valerius T, Slootstra JW, Mutis T, Bleeker WK, Anderson KC, Lokhorst HM, van de Winkel JG, Parren PW: Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011 Feb 1;186(3):1840-8. doi: 10.4049/jimmunol.1003032. Epub 2010 Dec 27. [Article]
- Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000. [Article]
- van der Veer MS, de Weers M, van Kessel B, Bakker JM, Wittebol S, Parren PW, Lokhorst HM, Mutis T: Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica. 2011 Feb;96(2):284-90. doi: 10.3324/haematol.2010.030759. Epub 2010 Nov 25. [Article]
- FDA Approved Drug Products: DARZALEX (daratumumab) injection, for intravenous use [Link]
- FDA Approved Drug Products: DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use [Link]
- External Links
- PubChem Substance
- 347910441
- 1721947
- ChEMBL
- CHEMBL1743007
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Daratumumab
- FDA label
- Download (417 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Approved for Marketing Not Available Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Completed Not Available Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Completed Not Available Multiple Myeloma (MM) / Newly Diagnosed / Preference, Patient / Satisfaction, Patient / Satisfaction, Personal / Transplant Ineligible 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Not Available Acute Kidney Injury (AKI) / Light Chain Nephropathy / Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Not Available High Risk / MRD / Multiple Myeloma (MM) / Newly Diagnosed 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 1800 MG Injection, solution, concentrate Intravenous 100 mg/5mL Injection, solution, concentrate Intravenous 20 MG/ML Injection, solution, concentrate Intravenous 20 mg/1ml Injection, solution, concentrate Intravenous; Parenteral 20 MG/ML Solution Intravenous 100 mg / 5 mL Solution Intravenous 400 mg / 20 mL Injection, solution, concentrate 100 mg/5ml Solution, concentrate Intravenous 20 mg Injection, solution Intravenous 20 mg/mL Injection, solution, concentrate 400 mg/20ml Solution Intravenous 20 mg/mL Injection Subcutaneous Solution Subcutaneous 1800 mg / 15 mL Injection, solution Subcutaneous 1800 mg/15mL Solution Subcutaneous 120 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2'-phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+) (PubMed:16690024). Has cADPR hydrolase activity (PubMed:7961800, PubMed:8253715)
- Specific Function
- identical protein binding
- Gene Name
- CD38
- Uniprot ID
- P28907
- Uniprot Name
- ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
- Molecular Weight
- 34328.145 Da
References
- de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, Oomen LA, Peipp M, Valerius T, Slootstra JW, Mutis T, Bleeker WK, Anderson KC, Lokhorst HM, van de Winkel JG, Parren PW: Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011 Feb 1;186(3):1840-8. doi: 10.4049/jimmunol.1003032. Epub 2010 Dec 27. [Article]
Drug created at November 18, 2015 17:34 / Updated at October 11, 2024 22:08