Filgrastim, sold under the brand name Neupogen among others, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

used to treat low neutrophil count. Low neutrophil counts may occur with

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

, following

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

or radiation poisoning, or be of an unknown cause. It may also be used to increase white blood cells for gathering during

leukapheresis Leukapheresis () is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remain ...

. It is given either by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

or under the skin. Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss. Severe side effects include

splenic rupture A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision. Signs and symptoms In minor injuries with little bleeding, there may be abdomin ...

and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

is safe for the baby. Filgrastim is a recombinant form of the naturally occurring

granulocyte colony-stimulating factor Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Functiona ...

(G-CSF). It works by stimulating the body to increase

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

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 WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Filgrastim

biosimilar A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved v ...

medications are available.

Medical uses

Filgrastim is used to treat

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteri ...

, stimulating the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

to increase production of

s. Causes of neutropenia include

and

bone marrow transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

Adverse effects

The most commonly observed adverse effect is mild bone pain after repeated administration, and local skin reactions at the site of injection.Neupogen 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 A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision. Signs and symptoms In minor injuries with little bleeding, there may be abdomin ...

(sometimes resulting in death), alveolar

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...

acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...

, and

hemoptysis Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. In other words, it is the airway bleeding. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia, a ...

. 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

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.

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).

Society and culture

Biosimilars

In 2015, Sandoz's filgrastim-sndz (trade name Zarxio), obtained the approval of the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) as a biosimilar. This was the first product to be passed under the

Biologics Price Competition and Innovation Act of 2009 The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) amends the Public Health Service Act (PHS Act) to create an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licen ...

(BPCI Act), as part of the

Affordable Care Act The Affordable Care Act (ACA), formally known as the Patient Protection and Affordable Care Act and colloquially known as Obamacare, is a landmark U.S. federal statute enacted by the 111th United States Congress and signed into law by Pres ...

. 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 (trade name Nivestym) was approved for use in the United States. 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. In 2016, Fraven was approved for use by Republic of Turkey ministry of health. Nivestym was approved for medical use in Canada in April 2020. In October 2021, Nypozi was approved for medical use in Canada.

Economics

Shortly after it was introduced, analyses of whether filgrastim is a cost-effective way of preventing

febrile neutropenia Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also ...

depended upon the clinical situation and the financial model used to pay for treatment. The longer-acting

pegfilgrastim Pegfilgrastim, sold under the brand name Neulasta among others, is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analog filgrastim. It serves to stimulate the production of white blood cells (neutrophils) ...

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.

References

External links

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