Filgrastim

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Not to be confused with granulocyte-macrophage colony-stimulating factor or epoetin alfa.

Filgrastim
Filgrastim.jpg
Clinical data
Trade namesNeupogen, Zarxio, Granix, Fraven, others
Other namesfilgrastim-aafi, filgrastim-sndz
AHFS/Drugs.comMonograph
MedlinePlusa692033
License data
Pregnancy
category
Routes of
administration		Intraveneous, subcutaneous
Drug classHematopoietic Agents
ATC code
Legal status
Legal status
  • US: ℞-only
  • EU: Rx-only
Identifiers
CAS Number
PubChem SID
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
ECHA InfoCard100.167.401 Edit this at Wikidata
Chemical and physical data
FormulaC845H1343N223O243S9
Molar mass18802.90 g·mol−1

Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count.[2] Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause.[2] It may also be used to increase white blood cells for gathering during leukapheresis.[2] It is given either by injection into a vein or under the skin.[2]

Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss.[2] Severe side effects include splenic rupture and allergic reactions.[2] It is unclear if use in pregnancy is safe for the baby.[2] Filgrastim is a recombinant-DNA form of the naturally occurring granulocyte colony-stimulating factor (G-CSF).[2] It works by stimulating the body to increase neutrophil production.[2]

Filgrastim was approved for medical use in the United States in 1991.[2] It is on the World Health Organization's List of Essential Medicines.[3] Filgrastim biosimilar medications are available.[2]

Medical uses[]

Filgrastim is used to treat neutropenia,[4] stimulating the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation.

Filgrastim is also used to increase the number of hematopoietic stem cells in the blood before collection by leukapheresis for use in hematopoietic stem cell transplantation.[medical citation needed]

Adverse effects[]

The most commonly observed adverse effect is mild bone pain after repeated administration,[5] and local skin reactions at the site of injection.[6][7] Other observed adverse effects include serious allergic reactions (including a rash over the whole body,[8] shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), ruptured spleen (sometimes resulting in death),[9] alveolar hemorrhage, acute respiratory distress syndrome, and hemoptysis.[6] Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders.[7]

Interactions[]

Drug interactions between filgrastim and other drugs have not been fully evaluated.[medical citation needed] Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution.[medical citation needed]

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes; this should be considered when interpreting bone-imaging results.[7]

Filgrastim has not been studied in pregnant women and its effects on the fetus is unknown. If taking filgrastim while pregnant, it is possible that traces of the drug could be found in the baby's blood. It is not known if the drug can get into human breast milk.[medical citation needed]

Mechanism of action[]

Filgrastim is a human granulocyte colony stimulating factor (G-CSF) produced by recombinant DNA technology. G-CSF regulates the production of neutrophils within the bone marrow; endogenous G-CSF is a glycoprotein produced by monocytes, fibroblasts, and endothelial cells.[medical citation needed]

G-CSF is a colony stimulating factor which has been shown to have minimal direct in vivo or in vitro effects on the production of other haematopoietic cell types. Neupogen (filgrastim) is the name for recombinant methionyl human granulocyte colony stimulating factor (r-metHuG-CSF).[7]

Production[]

It is produced by recombinant DNA technology. The gene for human granulocyte colony-stimulating factor is inserted into the genetic material of Escherichia coli. The G-CSF then produced by E. coli is different from G-CSF naturally made in humans.[citation needed]

Society and culture[]

Commercialization[]

Filgrastim is marketed under several brand names, including:

Company Brand
Cadila Pharmaceuticals Filcad
Abbott Laboratories Imumax
Dr. Reddy's Laboratories Grafeel
Intas Biopharmaceuticals Neukine
Amgen Neupogen[10][11]
Emcure Pharmaceuticals Emgrast
Religrast
Novartis/Sandoz Zarzio[12][13] and Zarxio[14]
Biocon Nufil
Pfizer Nivestim[15][16] and Nivestym[17]
Arven pharmaceuticals Fraven

Apricus Biosciences is currently[when?] developing and testing a product under the brand name Nupen which can deliver filgrastim through the skin to improve post-chemotherapy recovery of neutrophil counts.[citation needed]

Biosimilars[]

See also: Biosimilars

In 2015, Sandoz's filgrastim-sndz (trade name Zarxio), obtained the approval of the U.S. Food and Drug Administration (FDA) as a biosimilar.[14][18][19] This was the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), as part of the Affordable Care Act.[14] Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an "interchangeable" may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA said its approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.[19]

Zarxio is approved for the same indications as Neupogen, and can be prescribed by a health care professional for: patients with cancer receiving myelosuppressive chemotherapy; patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; patients with cancer undergoing bone marrow transplantation; patients undergoing autologous peripheral blood progenitor cell collection and therapy; and patients with severe chronic neutropenia.

— FDA, March 6, 2015

In 2018, filgrastim-aafi (trade name Nivestym) was approved for use in the United States.[17]

Neukine is an Indian biosimlar filgrastim and approved for the same indications as of Neupogen.[citation needed] Neukine is manufactured and marketed by Intas Pharmaceuticals Limited at Ahmedabad, India.[citation needed]

In September 2008, Ratiograstim, Tevagrastim, Biograstim, and Filgrastim ratiopharm were approved for use in the European Union.[20][21][22][23] Filgrastim ratiopharm was withdrawn in July 2011 and Biograstim was withdrawn in December 2016.

In February 2009, Filgrastim Hexal and Zarzio were approved for use in the European Union.[24][25]

In June 2010, Nivestim was approved for use in the European Union.[26]

In October 2013, Grastofil was approved for use in the European Union.[27]

In September 2014, Accofil was approved for use in the European Union.[28]

In 2016, Fraven was approved for use by Republic of Turkey ministry of health.[29]

Cost[]

Shortly after it was introduced, analyses of whether filgrastim is a cost-effective way of preventing febrile neutropenia depended upon the clinical situation and the financial model used to pay for treatment.[30] The longer-acting pegfilgrastim may in some cases be more cost-effective.[31] The introduction of biosimilars into the market resulted in a price reduction for the original, patent-protected product and increased use.[32]

See also[]

  • Granulocyte macrophage colony-stimulating factor, as a drug, (Sargramostim, trade name Leukine)
  • Immune system
  • Lipegfilgrastim (Lonquex), a PEGylated form of filgrastim
  • Pegfilgrastim (Neulasta), a PEGylated form of filgrastim

References[]

  1. ^ Jump up to: a b "Filgrastim Use During Pregnancy". Drugs.com. 13 September 2018. Retrieved 17 December 2019.
  2. ^ Jump up to: a b c d e f g h i j k "Filgrastim". The American Society of Health-System Pharmacists. Archived from the original on 10 May 2017. Retrieved 8 December 2016.
  3. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. ^ Crawford, J.; Glaspy, J. A.; Stoller, R. G.; Tomita, D. K.; Vincent, M. E.; McGuire, B. W.; Ozer, H. (2005). "Final Results of a Placebo-Controlled Study of Filgrastim in Small-Cell Lung Cancer: Exploration of Risk Factors for Febrile Neutropenia". Supportive Cancer Therapy. 3 (1): 36–46. doi:10.3816/SCT.2005.n.023. PMID 18632435.
  5. ^ Moore DC, Pellegrino AE (September 2017). "Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management". Ann Pharmacother. 51 (9): 797–803. doi:10.1177/1060028017706373. PMID 28423916. S2CID 33032446.
  6. ^ Jump up to: a b Neupogen "Neupogen: Patient Information Leaflet". Amgen. Archived from the original on 10 November 2013. Retrieved 24 June 2013.
  7. ^ Jump up to: a b c d "Neupogen- filgrastim injection, solution". DailyMed. 15 November 2019. Retrieved 20 December 2019.
  8. ^ Scott WR, Silberstein L, Flatley R, Ardeshna KM, Korostoff N, Dawe S (September 2009). "Cutaneous reaction to pegfilgrastim presenting as severe generalized skin eruption". Br. J. Dermatol. 161 (3): 717–9. doi:10.1111/j.1365-2133.2009.09371.x. PMID 19614649. S2CID 2655192.
  9. ^ Zimmer BM, Berdel WE, Ludwig WD, Notter M, Reufi B, Thiel E (March 1993). "Fatal spleen rupture during induction chemotherapy with rh GM-CSF priming for acute monocytic leukemia. Clinical case report and in vitro studies". Leuk. Res. 17 (3): 277–83. doi:10.1016/0145-2126(93)90012-a. PMID 8450676.
  10. ^ "Neupogen". U.S. Food and Drug Administration (FDA). Retrieved 20 December 2019.
  11. ^ "FDA Reviews What Could Be First Biosimilar". Discov. Dev. Mag. Rockaway, New Jersey, United States. Associated Press. 25 July 2014. Archived from the original on 29 July 2014.
  12. ^ "Zarzio EPAR". European Medicines Agency (EMA). Retrieved 20 December 2019.
  13. ^ "Zarzio 30 MU/0.5 ml solution for injection or infusion in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 4 July 2019. Retrieved 20 December 2019.
  14. ^ Jump up to: a b c "FDA approves first biosimilar product Zarxio". U.S. Food and Drug Administration (FDA) (Press release). 6 March 2015. Archived from the original on 11 December 2015. Retrieved 23 November 2015.
  15. ^ "Nivestim EPAR". European Medicines Agency (EMA). Retrieved 20 December 2019.
  16. ^ "Nivestim 12 MU/ 0.2 ml solution for injection/infusion - Summary of Product Characteristics (SmPC)". (emc). 18 December 2019. Retrieved 20 December 2019.
  17. ^ Jump up to: a b "Drug Approval Package: Nivestym (filgrastim-aafi)". U.S. Food and Drug Administration (FDA). 21 February 2019. Archived from the original on 20 December 2019. Retrieved 20 December 2019.
  18. ^ "Zarxio (filgrastim-sndz)". U.S. Food and Drug Administration (FDA). 20 April 2015. Archived from the original on 20 December 2019. Retrieved 20 December 2019.
  19. ^ Jump up to: a b Tavernise, Sabrina; Pollack, Andrew (6 March 2015). "F.D.A. Approves Zarxio, Its First Biosimilar Drug". The New York Times. Archived from the original on 23 October 2015. Retrieved 23 November 2015.
  20. ^ "Ratiograstim EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  21. ^ "Tevagrastim EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  22. ^ "Biograstim EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  23. ^ "Filgrastim ratiopharm EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  24. ^ "Filgrastim Hexal EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  25. ^ "Zarzio EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  26. ^ "Nivestim EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  27. ^ "Grastofil EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  28. ^ "Accofil EPAR". European Medicines Agency (EMA). Retrieved 2 April 2020.
  29. ^ [1] Arven ilaç, Türkiye’nin ilk biyobenzer ürününü üretti - Vatan Finans.
  30. ^ Neymark, Niels (1998). Assessing the Economic Value of Anticancer Therapies. Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 148. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 215–219. doi:10.1007/978-3-642-72123-6. ISBN 978-3-642-72123-6. OCLC 851760173. PMID 9670279. S2CID 34894897.
  31. ^ Ellery, Tony (2012). Pharmaceutical lifecycle management : making the most of each and every brand. Hansen, Neal. Hoboken, N.J.: John Wiley & Sons. p. 214. ISBN 978-1-118-26679-3. OCLC 797824835.
  32. ^ Cornes, Paul (9 April 2018). Biosimilars. Bennett, David. Abingdon. p. 54. ISBN 978-1-910797-67-9. OCLC 1064690227.

Further reading[]

  • Santoso B, van Boxtel CJ, Edwards RI, eds. (2001). Drug benefits and risks: international textbook of clinical pharmacology. New York: Wiley. ISBN 0-471-89927-5.

External links[]

  • "Filgrastim". Drug Information Portal. U.S. National Library of Medicine.
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