Filgrastim

Identification

Summary

Filgrastim 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

Accofil, Granix, Grastofil, Neupogen, Nivestim, Nivestym, Ratiograstim, Zarxio

Generic Name

Filgrastim

DrugBank Accession Number

DB00099

Background

Chemotherapy-induced neutropenia (CIN) is a common and serious complication of myelosuppressive chemotherapy. It is associated with significant morbidity and mortality and can increase the cost of cancer therapy. In these cases, colony stimulating factor is necessary to restore important cells for immune function ³.

For over twenty years, granulocyte colony-stimulating factors (G-CSFs; filgrastims) have been a pillar of treatment and prevention of CIN, and have been found to reduce the risk of neutropenia across various patient settings, decrease the incidence of febrile neutropenia, reduce the incidence of infection, reduce the requirement for treatment with antibiotics, and accelerate neutrophil recovery ³.

Filgrastim is a recombinant, non-pegylated human granulocyte colony stimulating factor (G-CSF) analog. It is marketed as the brand name Neupogen by Amgen (initially approved in 1998) and as Nivestym, a biosimilar agent by Pfizer. Nivestym was approved by the FDA on July 20th, 2018 ⁵. Between 1998 and the present, Neupogen/filgrastim has been approved for various indications ⁸.

Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting ¹⁰. On March 6, 2015, the FDA approved the biosimilar Zarxio (filgrastim-sndz) and is indicated for use in the same conditions as Neupogen. Zarxio is marketed by Sandoz ⁷.

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Haematopoietic growth factors

Protein Structure

Protein Chemical Formula: C₈₄₅H₁₃₄₃N₂₂₃O₂₄₃S₉
Protein Average Weight: 18800.0 Da

Sequences

>Amino acid sequence for filgrastim
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP

Download FASTA Format

Synonyms

Filgrastim
Filgrastim-aafi
Filgrastim-sndz
G-CSF
Granulocyte Colony Stimulating Factor
Tbo-filgrastim

Pharmacology

Indication

This drug is a leucocyte growth factor ^Label indicated to:

Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever ^Label.

Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment in patients with acute myeloid leukemia (AML) ^Label

Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) ^Label

Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis ^Label

Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia ^Label.

Neupogen is approved for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident ⁶.

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Associated Conditions

Associated Therapies

Mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis

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Pharmacodynamics

Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow ^Label. Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors, in turn, stimulating proliferation and differentiation ⁹.

G-CSF and its receptor are necessary for basal and stress-induced granulopoiesis, which forms neutrophils. Mice deficient in G-CSF or G-CSFR have severe neutropenia and reduced levels (~50%) of late-stage neutrophil precursors in the bone marrow under normal, resting conditions ⁴.

Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and enhances neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and enhanced expression of certain cell surface antigens). G-CSF is not species-specific and has demonstrated to have negligible direct in vivo or in vitro effects on the production or action of hematopoietic cell types other than the neutrophil and its lineage⁹.

Mechanism of action

As a G-CSF analog, this drug controls the proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and decreases their time to maturation. Filgrastim acts to increase the phagocytic activity of mature neutrophils, thus allowing them to prevent infection. In patients receiving cytotoxic chemotherapy, filgrastim may accelerate neutrophil recovery, leading to a reduction in the duration of the neutropenic phase post chemotherapy ^Label.

Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils, filgrastim acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. In one efficacy study, levels of neutrophils returned to baseline by 21 days following completion of chemotherapy and the administration of tbo-filgrastim (fast-acting) ¹⁰.

In phase 1 studies involving 96 patients with various non-myeloid malignancies‚ filgrastim administration resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day.

This increase in neutrophil counts was seen whether filgrastim was administered intravenous (1 to 70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous (SC) infusion (3 to 11 mcg/kg/day). After the discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within only 4 days after Nevistym was used ^Label.

Target	Actions	Organism
AGranulocyte colony-stimulating factor receptor	stimulator	Humans
UNeutrophil elastase	other/unknown	Humans

Absorption

Absorption and clearance of Neupogen follows first-order pharmacokinetics without concentration dependence. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2-8 hours ^Label. Filgrastim does not accumulate. It is estimated that when filgrastim is subcutaneously administered, the absolute bioavailability is approximately 62% and 71% for 375 mcg and 750 mcg doses respectively. When 5 mcg/kg tbo-filgrastim is subcutaneously administered, the absolute bioavailability is 33%. It takes 4-6 hours for tho-filgrastim to reach maximum concentration ¹⁰.

Volume of distribution

150 mL/kg ^Label

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Filgrastim products demonstrate nonlinear pharmacokinetics. The clearance is dependent on filgrastim product concentration in addition to neutrophil count. G-CSF receptor-mediated clearance is saturated by a high concentration of filgrastim products and is diminished by neutropenia. In addition, filgrastim products are cleared by the kidney ⁹.

Half-life

Elimination half-life was approximately 3.5 hours in both normal subjects and cancer subjects ^Label

Clearance

0.5 - 0.7 mL/minute/kg after SC administration of 3.45 mcg/kg and 11.5 mcg/kg in both normal subjects and cancer patients ^Label

Adverse Effects

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Toxicity

There are numerous adverse effects associated with Filgastrim. They are organized by organ system as follows:

Generalized effects

Serious allergic reactions, including anaphylaxis: Permanently discontinue NIVESTYM in patients with serious allergic reactions. With non-myeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are pyrexia, pain, rash, cough, and dyspnea ^Label. With AML (≥ 2% difference in incidence) are pain, epistaxis and rash ^Label. With severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are pain, anemia, epistaxis, diarrhea, hypoesthesia, and alopecia ^Label.

Musculoskeletal system

Exacerbation of arthritic symptoms has been uncommonly observed ⁹.

Spleen

Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. Cases of splenomegaly and splenic rupture have been reported uncommonly following administration of filgrastim. Some cases of splenic rupture were fatal ^Label.

Respiratory system

Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue filgrastim in patients with ARDS ^Label. Pulmonary adverse effects, in particular interstitial lung disease, have been reported after G-CSF administration. Patients with a recent history of lung infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs, such as cough, fever and dyspnea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of acute respiratory distress syndrome (ARDS). Filgrastim should be discontinued and appropriate treatment should be given ⁹.

Hematological system

Fatal sickle cell crises have occurred.

The granulocyte-colony stimulating factor can promote the malignant growth of myeloid cells in vitro and the same effects may be seen on some non-myeloid cells in vitro. The safety and efficacy of filgrastim administration in patients with myelodysplastic syndrome, or chronic myelogenous leukemia have not been established. Filgrastim is not indicated for use in these conditions. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukemia from acute myeloid leukemia ⁹.

Capillary leak syndrome has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, edema and hemoconcentration. Patients who show symptoms of capillary leak syndrome must be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care ⁹.

Leukocytosis (white blood cell (WBC) > 50 x 109/l) was seen in 41% of donors and transient thrombocytopenia (platelets < 100 x 109/l) following filgrastim and leukapheresis was observed in 35% of donors ⁹.

Renal system

This drug increases the risk of glomerulonephritis. Evaluate and consider dose-reduction or interruption of filgrastim if causality is likely ^Label.

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
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Bleomycin	The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Bleomycin.
Cyclophosphamide	The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Cyclophosphamide.
Topotecan	The risk or severity of neutropenia can be increased when Filgrastim is combined with Topotecan.
Vinblastine	The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinblastine.
Vincristine	The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincristine.
Vindesine	The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vindesine.
Vinflunine	The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinflunine.
Vinorelbine	The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinorelbine.

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Food Interactions

No interactions found.

Products

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International/Other Brands

Biocilin / Biofigran / Biofilgran / Endufil / Filatil / Filgen / Gran / Granulokine / Grimatin / Inmunef / Jiexin / Leucogen / Leucostim / Macroleuco / Neukine / Neutromax / Neutroval (Sicor Biotech) / Recombicyte / SciLocyte / Tevagastrim / White-C / Zarzio

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Accofil	Injection, solution	48000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	30000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	30000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	30000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	48000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	48000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	48000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	30000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	48000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable
Accofil	Injection, solution	30000000 U/0.5ml	Intravenous; Subcutaneous	Accord Healthcare S.L.U.	2016-09-07	Not applicable

Chemical Identifiers

UNII: PVI5M0M1GW
CAS number: 121181-53-1

References

Synthesis Reference

Tetsuro Kuga, Hiromasa Miyaji, Moriyuki Sato, Masami Okabe, Makoto Morimoto, Seiga Itoh, Motoo Yamasaki, Yoshiharu Yokoo, Kazuo Yamaguchi, Hajime Yoshida, Yoshinori Komatsu, "Method of producing a polypeptide having human granulocyte colony stimulating factor activity." U.S. Patent US5994518, issued February, 1988.

US5994518

General References

Wang B, Ludden TM, Cheung EN, Schwab GG, Roskos LK: Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. J Pharmacokinet Pharmacodyn. 2001 Aug;28(4):321-42. [Article]
Krzyzanski W, Wiczling P, Lowe P, Pigeolet E, Fink M, Berghout A, Balser S: Population modeling of filgrastim PK-PD in healthy adults following intravenous and subcutaneous administrations. J Clin Pharmacol. 2010 Sep;50(9 Suppl):101S-112S. doi: 10.1177/0091270010376966. [Article]
Kamioner D, Fruehauf S, Maloisel F, Cals L, Lepretre S, Berthou C: Study design: two long-term observational studies of the biosimilar filgrastim Nivestim (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia. BMC Cancer. 2013 Nov 16;13:547. doi: 10.1186/1471-2407-13-547. [Article]
Panopoulos AD, Watowich SS: Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine. 2008 Jun;42(3):277-88. doi: 10.1016/j.cyto.2008.03.002. Epub 2008 Apr 8. [Article]
FDA Approves Second Neupogen Biosimilar, Nivestym [Link]
FDA Approves Radiation Medical Countermeasure [Link]
Zarxio [Link]
Drugs Approved by the FDA document [Link]
EMA label [File]
TBO filgrastim [File]

External Links

UniProt: P09919
Genbank: X03438
KEGG Drug: D03235
PubChem Substance: 46505833
RxNav: 1433764
ChEMBL: CHEMBL1201567
Therapeutic Targets Database: DAP000113
PharmGKB: PA449626
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Filgrastim

FDA label

Download (2.27 MB)

MSDS

Download (125 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Diagnostic	Diabetes Mellitus	1
4	Completed	Prevention	Breast Cancer	1
4	Completed	Prevention	Mycoses	1
4	Completed	Supportive Care	Breast Cancer	1
4	Completed	Treatment	Anemia / Graft Versus Host Disease (GVHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes (MDS)	1
4	Completed	Treatment	Asherman's Syndrome / Endometrium; Atrophy, Cervix	1
4	Completed	Treatment	Burkitt's Lymphoma / Large Cell Anaplastic Lymphoma / Lymphoma, Lymphoblastic / Mediastinal Neoplasms	1
4	Completed	Treatment	Early Breast Cancer	2
4	Completed	Treatment	Leukemia, Lymphocytic, Acute, Adult	2
4	Completed	Treatment	Leukemia, Myeloblastic, Acute / Myelodysplastic Syndromes (MDS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Amgen Inc.
Physicians Total Care Inc.

Dosage Forms

Form	Route	Strength
Injection, solution	Intravenous; Subcutaneous	30000000 U/0.5ml
Injection, solution	Intravenous; Subcutaneous	48000000 U/0.5ml
Injection	Parenteral	30 MIO.E./0.5ML
Injection	Parenteral	0.5 ML
Injection	Parenteral	30 MIO E/0.5ML
Injection	Parenteral	48 MIO.E./0.5ML
Injection	Parenteral	48 MIO E/0.5ML
Solution	Intravenous; Subcutaneous	300 mcg
Solution	Intravenous; Subcutaneous	480 mcg
Injection, solution	Intravenous; Subcutaneous	30 MIU
Injection, solution	Intravenous; Subcutaneous	48 MIU
Injection, solution	Intravenous; Subcutaneous	60 MU/ml
Injection, solution	Intravenous; Subcutaneous	96 MU/ml
Injection	Parenteral	0.3 mg
Injection	Parenteral	0.48 mg
Injection	Intravenous
Solution		300 mcg/1ml
Injection, solution	Subcutaneous	300 ug/1mL
Injection, solution	Subcutaneous	480 ug/1.6mL
Injection, solution, concentrate	Intravenous; Subcutaneous
Injection, solution, concentrate	Subcutaneous
Injection, solution	Subcutaneous
Solution	Intravenous; Subcutaneous	300 mcg / 0.5 mL
Solution	Intravenous; Subcutaneous	480 mcg / 0.8 mL
Solution	Subcutaneous	300 mcg
Solution	Subcutaneous	480 mcg
Injection
Injection	Intravenous; Subcutaneous
Injection, solution		480 mcg/ml
Injection, solution
Injection, solution	Intravenous	300 ug/0.5mL
Injection, solution	Intravenous	300 ug/1mL
Injection, solution	Intravenous	480 ug/0.8mL
Solution	Intravenous; Subcutaneous	300 mcg / mL
Solution	Intravenous; Subcutaneous	600 mcg / mL
Injection	Parenteral	300 µg/0.5ml
Injection	Parenteral	30 MIO.E.
Injection	Parenteral	300 UG/1ML
Injection	Parenteral	480 µg/0.5ml
Injection	Parenteral	48 MIO.E.
Injection	Parenteral	480 UG
Injection	Parenteral	480 UG/0.5ML
Injection; solution	Intravenous; Subcutaneous
Solution	Intravenous; Subcutaneous	30 millions of units
Injection, solution		480 mcg/1vial
Injection, solution	Intravenous; Subcutaneous
Injection, solution	Intravenous; Subcutaneous	12000000 [units of filgrastim]/0.2mL
Injection, solution	Intravenous; Subcutaneous	30000000 [units of filgrastim]/0.5mL
Injection, solution	Intravenous; Subcutaneous	48000000 [units of filgrastim]/0.5mL
Injection	Parenteral	12 MIO E/0.2ML
Injection	Parenteral	0.2 ML
Injection, solution	Intravenous
Injection	Parenteral	05 ML
Injection, solution		120 mcg/0.2ml
Injection, solution	Intravenous; Subcutaneous	300 ug/1mL
Injection, solution	Intravenous; Subcutaneous	480 ug/1.6mL
Injection, solution	Subcutaneous	300 ug/0.5mL
Injection, solution	Subcutaneous	480 ug/0.8mL
Solution	Intravenous; Subcutaneous	480 mcg / 1.6 mL
Solution	Intravenous; Subcutaneous	300 cg
Injection	Parenteral	30 M UI/0.5 ml
Injection	Parenteral	48 M UI/0.8 ml
Injection	Parenteral	0.8 ML
Injection, solution	Intravenous; Subcutaneous	300 µg/0.5 ml
Injection, solution	Intravenous; Subcutaneous	480 µg/0.8 ml
Injection, solution	Intravenous; Subcutaneous	300 ug/0.5mL
Injection, solution	Intravenous; Subcutaneous	480 ug/0.8mL
Injection, solution	Intravenous; Subcutaneous	30 MU
Injection, solution	Intravenous; Subcutaneous	48 MU
Injection, solution		480 mcg/1ml
Injection	Parenteral	30 MIO E./0.5ML
Solution	Intravenous; Subcutaneous
Injection	Parenteral	48 MIO E./0.5ML
Solution	Intravenous; Subcutaneous	30 million IU
Injection, solution		10000 iu/10ml
Injection, solution		300 mcg/0.5ml
Injection, solution		480 mcg/0.5ml
Solution		300 mcg/1vial
Solution		480 mcg/1vial
Injection, solution		300 mcg/ml
Injection, solution		300 mcg/1ml

Prices

Unit description	Cost	Unit
Neupogen 480 mcg/0.8ml Solution 1 Box Contains Ten 0.8ml Syringes	4998.24USD	box
Neupogen 480 mcg/1.6ml Solution 1 Box Contains Ten 1.6ml Syringes	4554.58USD	box
Neupogen 300 mcg/0.5ml Solution 1 Box Contains Ten 0.5ml Syringes	3138.1USD	box
Neupogen 480 mcg/1.6 ml vial	437.94USD	ml
Neupogen 300 mcg/ml vial	286.04USD	vial

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
CA1339071	No	1997-07-29	2014-07-29

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	4	MSDS
boiling point (°C)	100	MSDS
hydrophobicity	0.209	Not Available
isoelectric point	5.65	Not Available

Targets

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Details1. Granulocyte colony-stimulating factor receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Stimulator

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. [Article]
Link DC, Kunter G, Kasai Y, Zhao Y, Miner T, McLellan MD, Ries RE, Kapur D, Nagarajan R, Dale DC, Bolyard AA, Boxer LA, Welte K, Zeidler C, Donadieu J, Bellanne-Chantelot C, Vardiman JW, Caligiuri MA, Bloomfield CD, DiPersio JF, Tomasson MH, Graubert TA, Westervelt P, Watson M, Shannon W, Baty J, Mardis ER, Wilson RK, Ley TJ: Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia. Blood. 2007 Sep 1;110(5):1648-55. Epub 2007 May 9. [Article]
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. [Article]
Ward AC: The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. Front Biosci. 2007 Jan 1;12:608-18. [Article]
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. [Article]
EMA label [File]
TBO filgrastim [File]

Details2. Neutrophil elastase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Other/unknown

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. [Article]
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. [Article]
Donini M, Fontana S, Savoldi G, Vermi W, Tassone L, Gentili F, Zenaro E, Ferrari D, Notarangelo LD, Porta F, Facchetti F, Notarangelo LD, Dusi S, Badolato R: G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007 Jun 1;109(11):4716-23. Epub 2007 Feb 20. [Article]
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. [Article]
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. [Article]
El Ouriaghli F, Fujiwara H, Melenhorst JJ, Sconocchia G, Hensel N, Barrett AJ: Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis. Blood. 2003 Mar 1;101(5):1752-8. Epub 2002 Oct 17. [Article]

Drug created on June 13, 2005 13:24 / Updated on July 29, 2021 06:27

Filgrastim

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References