Eflapegrastim
Identification
- Summary
Eflapegrastim is a form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive therapy.
- Brand Names
- Rolvedon
- Generic Name
- Eflapegrastim
- DrugBank Accession Number
- DB15001
- Background
Febrile neutropenia (FN), defined as the co-occurrence of fever (temperature > 38 ◦C) and severe neutropenia (ANC < 500 cells/mm3), is a potential side effect of myelosuppressive chemotherapy in which the patient develops an infection during a period of significant neutropenia.2 It typically develops during the first cycle of chemotherapy and is associated with an increased risk of morbidity and mortality. The primary factor associated with FN risk is the chemotherapy regimen being administered - regimens are classified as either high-, intermediate-, or low-risk for FN, and relevant guidelines recommend the use of pharmacologic prophylaxis against FN in patients receiving high-risk regimens and those receiving intermediate-risk regimens who have ≥1 additional risk factor.2
Granulocyte-colony stimulating factors (G-CSFs) - which include filgrastim and pegfilgrastim - were first used clinically in the 1990s and are the primary means of prophylaxis against chemotherapy-induced neutropenia, including FN.2 They trigger signaling pathways that control the differentiation, proliferation, migration, and survival of neutrophils, thereby helping to restore depressed neutrophil counts.3
Eflapegrastim is a form of recombinant human G-CSF comprising a human G-CSF analog coupled to the Fc fragment of human IgG4 via a polyethylene glycol linker.3 In September 2022, eflapegrastim was approved by the US FDA as a prophylactic against infection, as manifested by febrile neutropenia, in patients receiving certain myelosuppressive anti-cancer drugs.5
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Haematopoietic growth factors - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 72000.0 Da
- Sequences
>SUBUNIT_1 PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_2 PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_3 TPLGPASSLPQSFLLKSLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAP LSSCSSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQ MEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA FormatReferences:
- NIH Inxight: Eflapegrastim [Link]
- Synonyms
- Eflapegrastim
- External IDs
- HM-10460A
- HM10460A
- HNK-460
- HNK460
- SPL-2012
Pharmacology
- Indication
Eflapegrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.3
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Infection •••••••••••• ••••• ••••••••••• •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Eflapegrastim increases absolute neutrophil count (ANC) in a dose-dependent manner in both healthy subjects and cancer patients.3 In rat studies, it was associated with higher serum and bone marrow concentrations than pegfilgrastim, which translated to a significantly shorter duration of neutropenia when eflapegrastim was administered 24 hours post-chemotherapy compared to pegfilgrastim.2
- Mechanism of action
Eflapegrastim is a recombinant human granulocyte-colony stimulating factor (rhG-CSF). Like endogenous G-CSF, eflapegrastim binds to G-CSF receptors on myeloid progenitor cells and neutrophils - this triggers signaling pathways that result in neutrophil differentiation, proliferation, migration, and survival.3
Target Actions Organism AGranulocyte colony-stimulating factor receptor ligandHumans - Absorption
The Tmax of eflapegrastim is dose-dependent and increases with increasing dose.1 Following administration of the recommended dosage in patients with breast cancer, the median Tmax of eflapegrastim-xnst is 25 hours.3
- Volume of distribution
The volume of distribution of eflapegrastim-xnst is 1.44 L.3
- Protein binding
Not Available
- Metabolism
Eflapegrastim is likely metabolized via endogenous degradation following internalization by cells expressing G-CSF receptors.3
- Route of elimination
Following subcutaneous administration, eflapegrastim is not detectable in the urine.3,1
- Half-life
In patients with breast cancer, the geometric mean half-life of eflapegrastim-xnst is 36.4 hours.3
- Clearance
The clearance of eflapegrastim-xnst decreased with increasing dose, suggesting target-mediated clearance by neutrophils.3 With repeat dosing clearance appears to increase, potentially due to the subsequent increase in circulating neutrophils.3
- Adverse Effects
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- Toxicity
An overdose of eflapegrastim may result in leukocytosis and bone pain.3 In the event of an overdose, the patient should be monitored for adverse effects and general supportive measures should be implemented as necessary.
- 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 Eflapegrastim. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Eflapegrastim. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Eflapegrastim. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Eflapegrastim. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Eflapegrastim. - Food Interactions
- Not Available
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 Rolvedon Injection, solution 13.2 mg/0.6mL Subcutaneous Spectrum Pharmaceuticals, Inc. 2022-10-18 Not applicable US
Categories
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Biological Factors
- Blood Proteins
- Carbohydrates
- Colony-Stimulating Factors
- Cytokines
- Globulins
- Glycoconjugates
- Glycoproteins
- Granulocyte Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Immunoglobulin Constant Regions
- Immunoglobulin Fragments
- Immunoglobulins
- Immunoproteins
- Intercellular Signaling Peptides and Proteins
- Leukocyte Growth Factor
- Peptide Fragments
- Peptides
- 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
Chemical Identifiers
- UNII
- UT99UG9QJX
- CAS number
- 1384099-30-2
References
- General References
- Shin KH, Kim TE, Lim KS, Yoon SH, Cho JY, Kim SE, Park KM, Shin SG, Jang IJ, Yu KS: Pharmacokinetic and pharmacodynamic properties of a new long-acting granulocyte colony-stimulating factor (HM10460A) in healthy volunteers. BioDrugs. 2013 Apr;27(2):149-58. doi: 10.1007/s40259-013-0010-0. [Article]
- Blayney DW, Schwartzberg L: Chemotherapy-induced neutropenia and emerging agents for prevention and treatment: A review. Cancer Treat Rev. 2022 Sep;109:102427. doi: 10.1016/j.ctrv.2022.102427. Epub 2022 Jun 21. [Article]
- FDA Approved Drug Products: Rolvedon (eflapegrastim-xnst) for subcutaneous injection [Link]
- NIH Inxight: Eflapegrastim [Link]
- Cancer Network: FDA Approves Eflapegrastim Injection to Decrease Febrile Neutropenia–Related Infection in Non–Myeloid Malignancies [Link]
- External Links
- 2612526
- Wikipedia
- Eflapegrastim
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Breast Neoplasms 1 3 Completed Treatment Breast Cancer / Neutropenia 2 2 Completed Treatment Neutropenia 1 2 Recruiting Treatment Lymphoma / Solid Tumors 1 1 Completed Treatment Breast Cancer / Pharmacokinetics 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 13.2 mg/0.6mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Receptor activity
- Specific Function
- Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutroph...
- Gene Name
- CSF3R
- Uniprot ID
- Q99062
- Uniprot Name
- Granulocyte colony-stimulating factor receptor
- Molecular Weight
- 92155.615 Da
References
- FDA Approved Drug Products: Rolvedon (eflapegrastim-xnst) for subcutaneous injection [Link]
Drug created at May 20, 2019 14:41 / Updated at December 01, 2022 11:29