Filgrastim

Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count.<ref name=AHFS2016/> Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause.<ref name=AHFS2016/> It may also be used to increase white blood cells for gathering during leukapheresis.<ref name=AHFS2016/> It is given either by injection into a vein or under the skin.<ref name=AHFS2016/> Filgrastim is a leukocyte growth factor.<ref name="Neupogen FDA label" />

Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss.<ref name=AHFS2016/> Severe side effects include splenic rupture and allergic reactions.<ref name=AHFS2016/> It is unclear if use in pregnancy is safe for the baby.<ref name=AHFS2016/> Filgrastim is a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF).<ref name=AHFS2016/> It works by stimulating the body to increase neutrophil production.<ref name=AHFS2016/>

Filgrastim was approved for medical use in the United States in 1991.<ref name=AHFS2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref><ref name="WHO22nd">Template:Cite book</ref> Filgrastim biosimilar medications are available.<ref name=AHFS2016/>

Medical uses

Filgrastim is used to treat neutropenia;<ref name="Neupogen FDA label" /> acute myeloid leukemia;<ref name="Neupogen FDA label" /> nonmyeloid malignancies;<ref name="Neupogen FDA label" /> leukapheresis;<ref name="Neupogen FDA label" /> congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia;<ref name="Neupogen FDA label" /> and myelosuppressive doses of radiation.<ref name="Neupogen FDA label" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Tbo-filgrastim (Granix) is indicated for reduction in the duration of severe neutropenia in people with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.<ref name="Granix FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Adverse effects

The most commonly observed adverse effect is mild bone pain after repeated administration,<ref name="pmid28423916">Template:Cite journal</ref> and local skin reactions at the site of injection.<ref name="Neupogen FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Other observed adverse effects include serious allergic reactions (including a rash over the whole body,<ref name="pmid19614649">Template:Cite journal</ref> shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), ruptured spleen (sometimes resulting in death),<ref name="pmid8450676">Template:Cite journal</ref> alveolar hemorrhage, acute respiratory distress syndrome, and hemoptysis.<ref name="Neupogen FDA label" /> Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in people with sickle cell disorders.<ref name="Neupogen FDA label" />

Interactions

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.<ref name="Neupogen FDA label" />

Mechanism of action

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).<ref name="Neupogen FDA label" />

Society and culture

Biosimilars

In 2015, Sandoz's filgrastim-sndz (Zarxio), obtained the approval of the US Food and Drug Administration (FDA) as a biosimilar.<ref name="FDA_Zarxio_2015">Template:Cite press release</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="NYT_Zarxio">Template:Cite news</ref> 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.<ref name="FDA_Zarxio_2015" /> 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.<ref name="NYT_Zarxio" />

In 2018, filgrastim-aafi (Nivestym) was approved for use in the United States.<ref name="Nivestym Drug Approval Package">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2008, Ratiograstim, Tevagrastim, Biograstim, and Filgrastim ratiopharm were approved for use in the European Union.<ref name="Ratiograstim EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Biograstim EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Zarzio EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In June 2010, Nivestim was approved for use in the European Union.<ref name="Nivestim EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In October 2013, Grastofil was approved for use in the European Union.<ref name="Grastofil EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2014, Accofil was approved for use in the European Union.<ref name="Accofil EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In 2016, Fraven was approved for use by Republic of Turkey ministry of health.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Nivestym was approved for medical use in Canada in April 2020.<ref name="Nivestym SBD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In October 2021, Nypozi was approved for medical use in Canada.<ref name="Nypozi SBD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In February 2022, filgrastim-ayow (Releuko) was approved for medical use in the United States.<ref name="Releuko FDA label" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In June 2024, filgrastim-txid (Nypozi) was approved for medical use in the United States.<ref name="Nypozi FDA label">fda.gov Template:Bare URL PDF</ref>

In December 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zefylti, intended for the treatment of neutropenia and the mobilization of peripheral blood progenitor cells.<ref name="Zefylti EPAR" /> The applicant for this medicinal product is CuraTeQ Biologics s.r.o.<ref name="Zefylti EPAR" /> Zefylti is a biosimilar medicinal product.<ref name="Zefylti EPAR" /> It is highly similar to the reference product Neupogen (filgrastim), which has been authorized in various EU countries.<ref name="Zefylti EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Zefylti was authorized for medical use in the European Union in February 2025.<ref name="Zefylti PI">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Economics

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.<ref>Template:Cite book</ref> The longer-acting pegfilgrastim may in some cases be more cost-effective.<ref>Template:Cite book</ref>

Further reading

• Template:Cite journal
• Template:Cite book