Description

Simple

A medication used to increase the number of immune cells in the body to prevent infections after radiation or chemotherapy.

Clinical

A form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive therapy.

Overview

Chemotherapy-induced neutropenia (CIN) is a common and serious complication of myelosuppressive chemotherapy. It is associated with significant morbidity and mortality and can increase the cost of cancer therapy. In these cases, colony stimulating factor is necessary to restore important cells for immune function [3].

For over twenty years, granulocyte colony-stimulating factors (G-CSFs; filgrastims) have been a pillar of treatment and prevention of CIN, and have been found to reduce the risk of neutropenia across various patient settings, decrease the incidence of febrile neutropenia, reduce the incidence of infection, reduce the requirement for treatment with antibiotics, and accelerate neutrophil recovery [3].

Filgrastim is a recombinant, no... Read more

Pharmacology

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 fev... Read more

Pharmacodynamic

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 [ Read more

Mechanism of 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... Read more

Absorption

Absorption and clearance of Neupogen follows first-order pharmacokinetics without concentration dependence.
Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2-8 hours [FDA label]. Filgrastim do... Read more

Protein binding

Information currently not available.

Volume of distribution

150 mL/kg [FDA label]

Clearance

0.5 - 0.7 mL/minute/kg after SC administration of 3.45 mcg/kg and 11.5 mcg/kg in both normal subjects and cancer patients [FDA label]

Half life

Elimination half-life was approximately 3.5 hours in both normal subjects and cancer subjects [FDA label]

Route of elimination

Filgrastim products demonstrate nonlinear pharmacokinetics. The clearance is dependent on filgrastim product concentration in addition to neutrophil count. G-CSF receptor-mediated clearance is saturated by a high concentration of filgrastim products and is diminished by neutropenia. In addition, fil... Read more

Toxicity

There are numerous adverse effects associated with Filgastrim. They are organized by organ system as follows:

**Generalized effects**

Serious allergic reactions, including anaphylaxis: Permanently discontinue NIVESTYM in patients with serious allergic reactions.
With non-myeloid malignancie... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Filgrastim
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
Bleomycin
The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Bleomycin.
Cyclophosphamide
The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Cyclophosphamide.
Topotecan
The risk or severity of neutropenia can be increased when Filgrastim is combined with Topotecan.
Vinblastine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinblastine.
Vincamine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincamine.
Vincristine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincristine.
Vindesine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vindesine.
Vinflunine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinflunine.
Vinorelbine
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinorelbine.
Vintafolide
The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vintafolide.
10 References
  1. 1 . Wang B, Ludden TM, Cheung EN, Schwab GG, Roskos LK: Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. J Pharmacokinet Pharmacodyn. 2001 Aug;28(4):321-42.PubMed: 11677930
  2. 2 . Krzyzanski W, Wiczling P, Lowe P, Pigeolet E, Fink M, Berghout A, Balser S: Population modeling of filgrastim PK-PD in healthy adults following intravenous and subcutaneous administrations. J Clin Pharmacol. 2010 Sep;50(9 Suppl):101S-112S. doi: 10.1177/0091270010376966.PubMed: 20881223
  3. 3 . Kamioner D, Fruehauf S, Maloisel F, Cals L, Lepretre S, Berthou C: Study design: two long-term observational studies of the biosimilar filgrastim Nivestim (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia. BMC Cancer. 2013 Nov 16;13:547. doi: 10.1186/1471-2407-13-547.PubMed: 24237790
  4. 4 . Panopoulos AD, Watowich SS: Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine. 2008 Jun;42(3):277-88. doi: 10.1016/j.cyto.2008.03.002. Epub 2008 Apr 8.PubMed: 18400509
  5. 5 . FDA Approves Second Neupogen Biosimilar, Nivestym Link
  6. 6 . FDA Approves Radiation Medical Countermeasure Link
  7. 7 . Zarxio Link
  8. 8 . Drugs Approved by the FDA document Link
  9. 9 . EMA label File
  10. 10 . TBO filgrastim File