Filgrastim

Identification

Name
Filgrastim
Accession Number
DB00099 / PVI5M0M1GW
Groups
Accofil
Description

Chemotherapy-brought on neutropenia (CIN) is a common and extreme hardship of myelosuppressive chemotherapy. it's miles related to vast morbidity and mortality and can growth the fee of cancer therapy. In these cases, colony stimulating aspect is vital to restore crucial cells for immune function [A35591]. For over two decades, granulocyte colony-stimulating factors (G-CSFs; filgrastims) have been a pillar of treatment and prevention of CIN, and have been discovered to reduce the danger of neutropenia across numerous patient settings, lower the incidence of febrile neutropenia, reduce the occurrence of contamination, reduce the requirement for remedy with antibiotics, and boost up neutrophil healing [A35591]. Filgrastim is a recombinant, non-pegylated human granulocyte colony stimulating issue (G-CSF) analog. it's far marketed because the brand name _Neupogen_ with the aid of Amgen (to begin with accredited in 1998) and as _Nivestym_, a biosimilar agent by means of Pfizer. Nivestym was approved by the FDA on July twentieth, 2018 [L3735]. between 1998 and the prevailing, Neupogen/filgrastim has been accepted for diverse indications [L3744]. _Tbo-filgrastim_, which is advertised via Sicor Biotech and FDA approved on August 29, 2012, contains the same energetic element as Neupogen and is biologically comparable, however it's miles formulated to be short-performing [F719]. On March 6, 2015, the FDA approved the biosimilar Zarxio (filgrastim-sndz) and is indicated for use inside the identical situations as Neupogen. Zarxio is advertised through Sandoz [L3742].

Pharmacology

Pharmacodynamics

Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow [FDA label]. Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors, in turn, stimulating proliferation and differentiation [F714]. G-CSF and its receptor are necessary for basal and stress-induced granulopoiesis, which forms neutrophils. Mice deficient in G-CSF or G-CSFR have severe neutropenia and reduced levels (~50%) of late-stage neutrophil precursors in the bone marrow under normal, resting conditions [A35605]. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and enhances neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and enhanced expression of certain cell surface antigens). G-CSF is not species-specific and has demonstrated to have negligible direct in vivo or in vitro effects on the production or action of hematopoietic cell types other than the neutrophil and its lineage[F714].

Indication

This drug is a leucocyte growth factor [FDA label] indicated to: Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever [FDA label]. Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment in patients with acute myeloid leukemia (AML) [FDA label] Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) [FDA label] Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis [FDA label] Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia [FDA label]. Neupogen is approved for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident [L3739].

Action

As a G-CSF analog, this drug controls the proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and decreases their time to maturation. Filgrastim acts to increase the phagocytic activity of mature neutrophils, thus allowing them to prevent infection. In patients receiving cytotoxic chemotherapy, filgrastim may accelerate neutrophil recovery, leading to a reduction in the duration of the neutropenic phase post chemotherapy [FDA label]. Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils, filgrastim acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. In one efficacy study, levels of neutrophils returned to baseline by 21 days following completion of chemotherapy and the administration of tbo-filgrastim (fast-acting) [F719]. In phase 1 studies involving 96 patients with various non-myeloid malignancies‚ filgrastim administration resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day. This increase in neutrophil counts was seen whether filgrastim was administered intravenous (1 to 70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous (SC) infusion (3 to 11 mcg/kg/day). After the discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within only 4 days after Nevistym was used [FDA label].