|ATC code||L03AA02 (WHO)|
|Chemical and physical data|
|Molar mass||18802.8 g/mol|
Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes; it is a pharmaceutical analog of naturally occurring G-CSF. 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 was originally licensed by Amgen in 1991. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. In 2015 filgrastim became the first drug to have a biosimilar approved by the US FDA; that biosimilar's international nonproprietary name is filgrastim-sndz.
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).
Filgrastim is marketed under several brand names, including:
|Dr. Reddy's Laboratories||Grafeel|
|Reliance Life Sciences||Religrast|
|Novartis/Sandoz||Zarzio by Novartis or Zarxio by Sandoz a biosimilar product|
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.
On March 6, 2015, Sandoz’s filgrastim-sndz (trade name Zarxio), obtained the FDA's approval as a biosimilar to Amgen’s filgrastim (trade name Neupogen). 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
- Granulocyte macrophage colony-stimulating factor, as a drug, (Sargramostim ( Leukine)
- Pegfilgrastim (Neulasta, a PEGylated form of filgrastim)
- Beveridge, R. A.; Miller, J. A.; Kales, A. N.; Binder, R. A.; Robert, N. J.; Harvey, J. H.; Windsor, K.; Gore, I.; Cantrell, J.; Thompson, K. A.; Taylor, W. R.; Barnes, H. M.; Schiff, S. A.; Shields, J. A.; Cambareri, R. J.; Butler, T. P.; Meister, R. J.; Feigert, J. M.; Norgard, M. J.; Moraes, M. A.; Helvie, W. W.; Patton, G. A.; Mundy, L. J.; Henry, D.; Sheridan, B.; Staddon, A.; Ford, P.; Katcher, D.; Houck, W.; Major, W. B. (1998). "A Comparison of Efficacy of Sargramostim (Yeast-Derived RhuGM-CSF) and Filgrastim (Bacteria-Derived RhuG-CSF) in the Therapeutic Setting of Chemotherapy-Induced Myelosuppression". Cancer Investigation. 16 (6): 366–373. doi:10.3109/07357909809115775. PMID 9679526.
- "FDA approves first biosimilar product Zarxio", FDA, March 6, 2015, retrieved 23 November 2015
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- 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.
- Neupogen "Neupogen: Patient Information Leaflet". Amgen. Retrieved 24 June 2013.
- "NEUPOGEN® Patient Guide" (PDF). Amgen. Retrieved 24 June 2013.
- "Neupogen". RxList. 4 June 2012. Retrieved 23 June 2013.
- "FDA Reviews What Could Be First Biosimilar". Discov. Dev. Mag. Rockaway, New Jersey, United States. Associated Press. 25 July 2014.
- Tavernise, Sabrina; Pollack, Andrew (March 6, 2015). "F.D.A. Approves Zarxio, Its First Biosimilar Drug". New York Times. Retrieved 23 November 2015.
- Budiono Santoso; Chris J. van Boxtel; Boxtel, Christoffel Jos van (2001). Drug benefits and risks: international textbook of clinical pharmacology. New York: Wiley. ISBN 0-471-89927-5.
- "Neupogen information". Retrieved 20 October 2005.