Pegfilgrastim
Identification
- Name
- Pegfilgrastim
- Accession Number
- DB00019
- Description
Pegfilgrastim is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (G-CSF) analogue, filgrastim.2 It is used to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with with non-myeloid cancer receiving myelosuppressive anti-cancer treatment. Some patients with greater risk factors may develop febrile neutropenia from myelosuppressive therapy and are susceptible to an increased risk of developing infections. Although the risk of developing febrile neutropenia is less than 20% in many readily used chemotherapy regimens,9 infections pose risks of hospitalization and mortalities.4 Due to the relatively short circulating half-life of filgrastim, a 20 kDa PEG moiety was covalently conjugated to the N-terminus of filgrastim (at the methionine residue) to develop a longer acting version of the drug.1,3 Due to a longer half-life and slower elimination rate than filgrastim, pegfilgrastim requires less frequent dosing than filgrastim. However, pegfilgrastim retains the same biological activity as filgrastim and binds to the same G-CSF receptor to stimulate the proliferation, differentiation, and activation of neutrophils.3
First developed by Amgen, pegfilgrastim was initially approved by the FDA in 2002 and marketed as Neulasta®. It is typically administered via a subcutaneous injection. There are several pegfilgrastim biosimilars (Fulphila®, Pelgraz® or Lapelga®, Pelmeg®, Udenyca®, Ziextenzo®, and Grasustek®) that are approved for the same therapeutic indication by Health Canada, European Union (EU), and FDA.8,10 These biosimilars are highly similar to the reference product, Neulasta®, in terms of pharmacological and pharmacokinetic profile and condition(s) of use, such as the therapeutic indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration.11
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Haematopoietic growth factors - Protein Structure
- Protein Chemical Formula
- C845H1343N223O243S9
- Protein Average Weight
- 39000.0 Da (approximate, PEGylated)
- Sequences
> Pegfilgrastim sequence MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA Format- Synonyms
- Granulocyte colony-stimulating factor pegfilgrastim
- peg-filgrastim
- Pegfilgrastim
- pegfilgrastim-apgf
- pegfilgrastim-bmez
- pegfilgrastim-cbqv
- pegfilgrastim-jmdb
Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Indication
Pegfilgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.6
It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).6
- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Pegfilgrastim is a recombinant human granulocyte colony-stimulating factor (G-CSF) that promotes the production, proliferation, and maturation of neutrophils, which are white blood cells involved in both innate and adaptive immune responses.4,9 The safety and efficacy of pegfilgrastim in reducing the risk of febrile neutropenia and infections have been demonstrated in various tumor types and settings.4
During chemotherapy-induced neutropenia, the clearance of pegfilgrastim is significantly reduced and the concentration of pegfilgrastim is sustained until the onset of neutrophil recovery.1 Serum concentrations of pegfilgrastim decline as the neutrophil count increases as neutrophil and neutrophil precursors are involved in cell-mediated clearance of the drug.2 Due the addition of polyethylene glycol group to its structure, Pegfilgrastim is a long-acting form of filgrastim with an extended serum half-life and reduced renal clearance.3 Although it is more slowly absorbed than filgrastim, self-regulation of pegfilgrastim is more efficient and the drug effects are maintained during one chemotherapy cycle (2-3 weeks).1
- Mechanism of action
Neutrophils are short-lived immune cells that are highly susceptible to cell death following myelosuppressive chemotherapy. This marked reduction in neutrophil numbers during chemotherapy increases the risk of hospitalization, infection, and infection-related mortality. It also directly impacts the clinical outcome of patients if cases of febrile neutropenia requires dose reductions or schedule delay of chemotherapy, thus reducing the clinical efficacy of chemotherapy and patient benefit from receiving appropriate treatment.4
G-CSF is an endogenous haematopoietic growth factor that stimulates granulopoietic cells of the neutrophil lineage. Pegfilgrastim mimics its biological actions and binds to the same G-CSF receptor expressed on cells of myeloid lineage, such as granulocytic precursors and mature neutrophils.1 Upon binding of the ligand, G-CSF receptor undergoes a conformational change and activates several downstream signalling pathways including JAK/STAT, PI3K/AKT and MAPK/ERK.5 These pathways work to increase proliferation and differentiation of granulocyte progenitor cells, induce maturation of the progenitor cells, and enhance survival and function of mature neutrophils.1
Target Actions Organism AGranulocyte colony-stimulating factor receptor agonistHumans - Absorption
Pegfilgrastim has a lower absolute bioavailability than filgrastim following subcutaneous administration. The absorption of pegfilgrastim is largely dependent on the lymphatic system due to the attached PEG group contributing to the large size of the drug. It is slowly absorbed following subcutaneous administration with a time to peak concentration (Tmax) of about 1-2 days.1
- Volume of distribution
Pegfilgrastim appears to have a volume of distribution of approximately 170L.[A33290]
- Protein binding
The plasma protein binding of pegfilgrastim is unlikely.12
- Metabolism
It is not know whether pegfilgrastim is metabolized into major metabolites.12 Once it binds to the therapeutic target, pegfilgrastim is internalized by the neutrophil and undergoes nonspecific degradation.1
- Route of elimination
The polyethylene glycol moiety limits the renal clearance by glomerular filtration of pegfilgrastim, making neutrophil-mediated clearance as the predominant route of elimination.3 This elimination pathway is initiated by the binding of pegfilgrastim to the G-CSF receptor on the neutrophil cell surface, leading to the internalization of the pegfilgrastim-receptor complex via endocytosis and subsequent degradation inside the cell. While hepatic clearance has not been well characterized for pegfilgrastim, its non-PEGylated precursor filgrastim is known to be unaffected by changes in hepatic clearance.1
- Half-life
The serum half-life of Pegfilgrastim is highly variable depending on the absolute neutrophil count, with the range of 15 to 80 hours following subcutaneous administration. The median serum half-life of 42 hours.3,6
- Clearance
Pegfilgrastim has a self-regulating clearance that involves neutrophil-induced clearance.1,4 The clearance is dependent on the number of neutrophils and body weight of the patient: the clearance increases with increasing number of granulocytes and lower body weights.6 Pegfilgrastim is not eliminated from the circulation until neutrophils start to recover following chemotherapy-induced neutropenia and its clearance is increased as neutrophil counts also increase.4 The apparent serum clearance is 14 mL/h/kg.12
- Adverse Effects
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The maximum safe dose of pegfilgrastim has not been established; however, the highest dose used in clinical trials was 300 mcg/kg.9 Overdosage of pegfilgrastim may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who self-administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for signs and symptoms of toxicity and responded with appropriate general supportive care.6,9
- Affected organisms
- Humans and other mammals
- 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 softwareAntihemophilic factor (recombinant), PEGylated The therapeutic efficacy of Antihemophilic factor (recombinant), PEGylated can be decreased when used in combination with Pegfilgrastim. Certolizumab pegol The therapeutic efficacy of Certolizumab pegol can be decreased when used in combination with Pegfilgrastim. Cyclophosphamide The risk or severity of pulmonary toxicity can be increased when Pegfilgrastim is combined with Cyclophosphamide. Damoctocog alfa pegol The therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Pegfilgrastim. Elapegademase The therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegfilgrastim. Lipegfilgrastim The therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Pegfilgrastim. Methoxy polyethylene glycol-epoetin beta The therapeutic efficacy of Methoxy polyethylene glycol-epoetin beta can be decreased when used in combination with Pegfilgrastim. Nonacog beta pegol The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Pegfilgrastim. Pegademase The therapeutic efficacy of Pegademase can be decreased when used in combination with Pegfilgrastim. Pegaptanib The therapeutic efficacy of Pegaptanib can be decreased when used in combination with Pegfilgrastim. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cegfila Injection, solution 6 mg Subcutaneous Mundipharma Corporation (Ireland) Limited 2020-12-16 Not applicable EU 
Fulphila Solution 10 mg Subcutaneous Bgp Pharma Ulc 2020-02-07 Not applicable Canada 
Fulphila Injection 6 mg/0.6mL Subcutaneous Mylan Institutional LLC 2018-07-09 Not applicable US 
Fulphila Injection, solution 6 mg Subcutaneous Mylan S.A.S. 2020-12-16 Not applicable EU Fulphila Injection, solution 6 mg Subcutaneous Mylan S.A.S. 2020-12-16 Not applicable EU Grasustek Injection, solution 6 mg Subcutaneous Juta Pharma Gmb H 2020-12-16 Not applicable EU Lapelga Solution Subcutaneous Apotex Corporation 2019-02-27 Not applicable Canada Neulasta Injection, solution 6 mg Subcutaneous Amgen Europe B.V. 2020-12-16 Not applicable EU Neulasta Kit 6 mg/0.6mL Subcutaneous AMGEN INC 2002-04-01 Not applicable US Neulasta Injection, solution 6 mg Subcutaneous Amgen Europe B.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- L03AA13 — Pegfilgrastim
- Drug Categories
- Adjuvants, Immunologic
- Alcohols
- Amino Acids, Peptides, and Proteins
- Antineoplastic and Immunomodulating Agents
- Biological Factors
- Carbohydrates
- Colony-Stimulating Factors
- Compounds used in a research, industrial, or household setting
- Cytokines
- Ethylene Glycols
- Glycoconjugates
- Glycols
- Glycoproteins
- Granulocyte Colony-Stimulating Factors
- Hematinics
- Hematopoietic Cell Growth Factors
- Increased Myeloid Cell Production
- Intercellular Signaling Peptides and Proteins
- Leukocyte Growth Factor
- Macromolecular Substances
- Pegylated agents
- Peptides
- Polymers
- Proteins
- 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
Chemical Identifiers
- UNII
- 3A58010674
- CAS number
- 208265-92-3
References
- General References
- Yang BB, Kido A: Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet. 2011 May;50(5):295-306. doi: 10.2165/11586040-000000000-00000. [PubMed:21456630]
- Curran MP, Goa KL: Pegfilgrastim. Drugs. 2002;62(8):1207-13; discussion 1214-5. doi: 10.2165/00003495-200262080-00012. [PubMed:12010086]
- Molineux G: The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des. 2004;10(11):1235-44. doi: 10.2174/1381612043452613. [PubMed:15078138]
- Arvedson T, O'Kelly J, Yang BB: Design Rationale and Development Approach for Pegfilgrastim as a Long-Acting Granulocyte Colony-Stimulating Factor. BioDrugs. 2015 Jun;29(3):185-98. doi: 10.1007/s40259-015-0127-4. [PubMed:25998211]
- Dwivedi P, Greis KD: Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies. Exp Hematol. 2017 Feb;46:9-20. doi: 10.1016/j.exphem.2016.10.008. Epub 2016 Oct 24. [PubMed:27789332]
- Neulasta (pegfilgrastim) - FDA Label [Link]
- Neulasta Safety Data Sheet - Amgen [Link]
- Biosimilars of pegfilgrastim [Link]
- Pegfilgrastim - StatPearls - NCBI Bookshelf [Link]
- EMA approval for pegfilgrastim biosimilar Grasustek [Link]
- Biosimilar and Interchangeable Products | FDA [Link]
- pegfilgrastim | Cancer Care Ontario [Link]
- External Links
- UniProt
- P09919
- Genbank
- X03438
- KEGG Drug
- D06889
- PubChem Substance
- 46505853
- 338036
- ChEMBL
- CHEMBL1201568
- Therapeutic Targets Database
- DAP000395
- PharmGKB
- PA164781387
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pegfilgrastim
- AHFS Codes
- 20:16.00 — Hematopoietic Agents
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Prevention Breast Cancer 2 4 Completed Prevention Breast Cancer / Lung Cancers / Neutropenia / Non-Hodgkin's Lymphoma (NHL) / Ovarian Cancer 1 4 Completed Prevention Malignant Lymphomas 1 4 Completed Prevention Malignant Solid Tumours 1 4 Completed Treatment Breast Cancer 1 4 Completed Treatment Non-Hodgkin's Lymphoma (NHL) 1 4 Completed Treatment Non-Small Cell Lung Carcinoma (NSCLC) 1 4 Not Yet Recruiting Treatment Early Breast Cancer 1 4 Unknown Status Supportive Care Breast Cancer / Neutropenia 1 3 Active Not Recruiting Supportive Care Chemotherapy Induced Neutropenia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Amgen Inc.
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Injection Subcutaneous 6 mg/0.6mL Injection, solution Subcutaneous Kit Subcutaneous 6 mg/0.6mL Solution Parenteral; Subcutaneous Solution Subcutaneous 10 mg Injection Subcutaneous Solution Subcutaneous 6 mg Injection, solution Subcutaneous 6 mg Solution Subcutaneous Solution Injection, solution Parenteral; Subcutaneous Injection, solution Subcutaneous 6 mg/0.6mL Injection, solution - Prices
Unit description Cost Unit Neulasta 6 mg/0.6 ml syringe 4102.37USD syringe Neulasta 6 mg/0.6ml Solution 0.6ml Syringe 4026.05USD syringe DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA1341537 No 2007-07-31 2024-07-31 Canada CA1339071 No 1997-07-29 2014-07-29 Canada
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 60 °C Luo, P., Protein Science 11:1218-1226 (2002)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- 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
- Erkeland SJ, Aarts LH, Irandoust M, Roovers O, Klomp A, Valkhof M, Gits J, Eyckerman S, Tavernier J, Touw IP: Novel role of WD40 and SOCS box protein-2 in steady-state distribution of granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation and differentiation signaling. Oncogene. 2007 Mar 29;26(14):1985-94. Epub 2006 Sep 25. [PubMed:17001306]
- Elsasser A, Franzen M, Kohlmann A, Weisser M, Schnittger S, Schoch C, Reddy VA, Burel S, Zhang DE, Ueffing M, Tenen DG, Hiddemann W, Behre G: The fusion protein AML1-ETO in acute myeloid leukemia with translocation t(8;21) induces c-jun protein expression via the proximal AP-1 site of the c-jun promoter in an indirect, JNK-dependent manner. Oncogene. 2003 Aug 28;22(36):5646-57. [PubMed:12944913]
- Ward AC: The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. Front Biosci. 2007 Jan 1;12:608-18. [PubMed:17127322]
- Zhuang D, Qiu Y, Haque SJ, Dong F: Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1. J Leukoc Biol. 2005 Oct;78(4):1008-15. Epub 2005 Jul 20. [PubMed:16033816]
- Cao YR, Shao ZH, Liu H, Shi J, Bai J, Tu MF, Wang HQ, Xing LM, Cui ZZ, Sun J, Jia HR, Yang TY: [The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients]. Zhonghua Xue Ye Xue Za Zhi. 2005 Apr;26(4):235-8. [PubMed:15949269]
- Kotto-Kome AC, Fox SE, Lu W, Yang BB, Christensen RD, Calhoun DA: Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res. 2004 Jul;50(1):55-8. [PubMed:15082029]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
- Gene Name
- ELANE
- Uniprot ID
- P08246
- Uniprot Name
- Neutrophil elastase
- Molecular Weight
- 28517.81 Da
References
- Carter CR, Whitmore KM, Thorpe R: The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to human neutrophil elastase degradation. J Leukoc Biol. 2004 Mar;75(3):515-22. Epub 2003 Dec 4. [PubMed:14657210]
- Jian MY, Koizumi T, Tsushima K, Fujimoto K, Kubo K: Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats. Inflammation. 2004 Dec;28(6):327-36. [PubMed:16245075]
- Pelus LM, Bian H, King AG, Fukuda S: Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRObeta/CXCL2 and GRObetaT/CXCL2delta4. Blood. 2004 Jan 1;103(1):110-9. Epub 2003 Sep 4. [PubMed:12958067]
- Druhan LJ, Ai J, Massullo P, Kindwall-Keller T, Ranalli MA, Avalos BR: Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia. Blood. 2005 Jan 15;105(2):584-91. Epub 2004 Sep 7. [PubMed:15353486]
- Schepers H, Wierenga AT, van Gosliga D, Eggen BJ, Vellenga E, Schuringa JJ: Reintroduction of C/EBPalpha in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis. Blood. 2007 Aug 15;110(4):1317-25. Epub 2007 May 2. [PubMed:17475913]
- Abdolzade-Bavil A, von Kerczek A, Cooksey BA, Kaufman T, Krasney PA, Pukac L, Gorlach M, Lammerich A, Scheckermann C, Allgaier H, Shen WD, Liu PM: Differential sensitivity of lipegfilgrastim and pegfilgrastim to neutrophil elastase correlates with differences in clinical pharmacokinetic profile. J Clin Pharmacol. 2016 Feb;56(2):186-94. doi: 10.1002/jcph.578. Epub 2015 Sep 1. [PubMed:26105553]
Drug created on June 13, 2005 13:24 / Updated on April 11, 2021 00:58