|Trade names||Neupogen, Zarxio, others|
|Chemical and physical data|
|Molar mass||18802.8 g/mol g·mol−1|
Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may also be used to increase white blood cells for gathering during leukapheresis. It is given either by injection into a vein or under the skin.
Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss. Severe side effects include splenic rupture and allergic reactions. It is unclear if use in pregnancy is safe for the baby. Filgrastim is a recombinant-DNA form of the naturally occurring granulocyte colony-stimulating factor (G-CSF). It works by stimulating the body to increase neutrophil production.
Filgrastim was approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$3.95 to US$94.66 per dose. In the United Kingdom it cost the NHS about £50.15 per 300 μg dose. In the United States treatment costs more than US$200. Filgrastim biosimilar medications are also available.
The most commonly observed adverse effect is mild bone pain after repeated administration, and local skin reactions at the site of injection. Other observed adverse effects include serious allergic reactions (including a rash over the whole body, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), ruptured spleen (sometimes resulting in death), alveolar hemorrhage, acute respiratory distress syndrome, and hemoptysis. Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders.
Drug interactions between filgrastim and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution.
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.
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.
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.
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).
Society and culture
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.
Filgrastim is marketed under several brand names, including:
|Dr. Reddy's Laboratories||Grafeel|
|Reliance Life Sciences||Religrast|
|Novartis/Sandoz||Zarzio or Zarxio|
Apricus Biosciences is currently 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.
In 2015, Sandoz's filgrastim-sndz (trade name Zarxio), obtained the FDA's approval as a biosimilar. This is the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), as part of President Obama's March 2010 Affordable Care Act. 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.
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
Neukine is an Indian biosimlar filgrastim and approved for the same indications as of Neupogen. Neukine is manufactured and marketed by Intas Pharmaceuticals Limited at Ahmedabad, India.
- Granulocyte macrophage colony-stimulating factor, as a drug, (Sargramostim) ( Leukine)
- Pegfilgrastim (Neulasta, a PEGylated form of filgrastim)
- immune system
- "Filgrastim". The American Society of Health-System Pharmacists. Archived from the original on 10 May 2017. Retrieved 8 December 2016.
- "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
- "Filgrastim". International Drug Price Indicator Guide. Archived from the original on 10 May 2017. Retrieved 8 December 2016.
- "Filgrastim- ERC: International Drug Price Indicator Guide". erc.msh.org. Archived from the original on 10 May 2017. Retrieved 19 December 2016.
- British national formulary: BNF 69 (69 ed.). British Medical Association. 2015. p. 678. ISBN 9780857111562.
- Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 292. ISBN 9781284057560.
- 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.
- 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.
- Neupogen "Neupogen: Patient Information Leaflet". Amgen. Archived from the original on 10 November 2013. Retrieved 24 June 2013.
- 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.
- 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.
- "NEUPOGEN® Patient Guide" (PDF). Amgen. Archived from the original (PDF) on 10 November 2013. Retrieved 24 June 2013.
- "Neupogen". RxList. 4 June 2012. Archived from the original on 2 July 2013. Retrieved 23 June 2013.
- "Archived copy" (PDF). Archived (PDF) from the original on 2015-12-22. Retrieved 2014-08-18.CS1 maint: archived copy as title (link)
- "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.
- "FDA approves first biosimilar product Zarxio", FDA, March 6, 2015, archived from the original on 11 December 2015, retrieved 23 November 2015
- Tavernise, Sabrina; Pollack, Andrew (March 6, 2015). "F.D.A. Approves Zarxio, Its First Biosimilar Drug". New York Times. Archived from the original on 23 October 2015. Retrieved 23 November 2015.