Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analogue used to stimulate the proliferation and differentiation of granulocytes;[3] it is a pharmaceutical analogue 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.

Amgen originally licenced filgrastim (trade name Neupogen) in 1991.[4]

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[5]

Medical uses

Filgrastim is used to treat neutropenia,[7] stimulating the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation.

Filgrastim is additionally 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.[8] 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.[8] Severe sickle cell crises, in a few cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders.[9]

Interactions

Drug interactions between filgrastim and additional drugs haven't been fully evaluated. Drugs which might potentiate the release of neutrophils‚ like 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.[10]

Filgrastim hasn't been studied in pregnant women and its effects on the foetus is unknown. If taking filgrastim while pregnant, it is possible that traces of the drug can be found in the baby's blood. It isn't 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 additional haematopoietic cell types. NEUPOGEN (filgrastim) is the name for recombinant methionyl human granulocyte colony stimulating factor (r-metHuG-CSF).[11]

Commercialization

Filgrastim is marketed under several brand names, including:

CompanyBrand
Cadila PharmaceuticalsFilcad
Abbott LaboratoriesImumax
Dr. Reddy's LaboratoriesGrafeel
Intas BiopharmaceuticalsNeukine
AmgenNeupogen[12]
Emcure PharmaceuticalsEmgrast
Reliance Life SciencesReligrast
NovartisZarzio or Zarxio, a biosimilar product[4]
BioconNufil

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.

Zarxio

On March 6, 2015, Sandoz’s filgrastim-sndz (trade name Zarxio), obtained the FDA's approval as a biosimilar[4][13] 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.[4] 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” might 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 additional clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.[13]

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 leukaemia 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