Filgrastim


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. 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. Filgrastim biosimilar medications are available.

Medical uses

Filgrastim is used to treat neutropenia, 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.

Adverse effects

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, ruptured spleen, 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.

Interactions

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 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 is the name for recombinant methionyl human granulocyte colony stimulating factor.

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.

Society and culture

Commercialization

Filgrastim is marketed under several brand names, including:
CompanyBrand
Cadila PharmaceuticalsFilcad
Abbott LaboratoriesImumax
Dr. Reddy's LaboratoriesGrafeel
Intas BiopharmaceuticalsNeukine
AmgenNeupogen
Emcure PharmaceuticalsEmgrast
Reliance Life SciencesReligrast
Novartis/SandozZarzio and Zarxio
BioconNufil
PfizerNivestim and Nivestym

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.

Biosimilars

In 2015, Sandoz's filgrastim-sndz, obtained the approval of the U.S. Food and Drug Administration as a biosimilar. This was the first product to be passed under the Biologics Price Competition and Innovation Act of 2009, as part of the 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.
In 2018, filgrastim-aafi was approved for use in the United States.
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.
In September 2008, Ratiograstim, Tevagrastim, Biograstim, and Filgrastim ratiopharm were approved for use in the European Union. 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.
In June 2010, Nivestim was approved for use in the European Union.
In October 2013, Grastofil was approved for use in the European Union.
In September 2014, Accofil was approved for use in the European Union.

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. The longer-acting pegfilgrastim may in some cases be more cost-effective. The introduction of biosimilars into the market resulted in a price reduction for the original, patent-protected product and increased use.