Usage
Granulocyte Colony Stimulating Factor (G-CSF) is prescribed to stimulate the production of neutrophils (a type of white blood cell) in the bone marrow. It is primarily used in patients undergoing chemotherapy to counteract neutropenia (low neutrophil count), a common side effect that increases the risk of infections. G-CSF is also used to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood for collection and subsequent transplantation. Additionally, it’s used in patients with certain congenital or acquired neutropenias to boost neutrophil counts and reduce infection risk.
It is classified as a hematopoietic growth factor and immunostimulant.
G-CSF exerts its effects by binding to specific receptors on the surface of myeloid progenitor cells in the bone marrow. This binding triggers intracellular signaling pathways that promote the proliferation, differentiation, and maturation of these cells into neutrophils, thereby increasing their numbers in the bloodstream.
Alternate Names
G-CSF is also known as Granulocyte-Colony Stimulating Factor.
Brand names for filgrastim, a type of G-CSF, include: Neupogen, Zarzio, Nivestym, Granix.
Brand names for pegfilgrastim, a long-acting G-CSF, include: Neulasta, Pelmeg, Ziextenco.
Lenograstim is another type of G-CSF marketed under the brand name Granocyte.
How It Works
Pharmacodynamics: G-CSF primarily acts on hematopoietic progenitor cells, stimulating the production and release of neutrophils from the bone marrow. It also enhances the function of mature neutrophils, including their ability to phagocytose (engulf) and destroy bacteria.
Pharmacokinetics: G-CSF is administered subcutaneously or intravenously. Following subcutaneous administration, it is absorbed relatively slowly, reaching peak serum concentrations within 2 to 8 hours. G-CSF is primarily eliminated through the kidneys and liver by metabolism. Its half-life varies depending on the dosage and administration route.
Mode of Action: G-CSF binds to the G-CSF receptor, a transmembrane protein expressed on the surface of myeloid progenitor cells. This binding activates intracellular signaling cascades, including the JAK/STAT and MAPK pathways, which regulate gene expression and ultimately drive neutrophil production.
Receptor Binding and Signal Transduction: G-CSF binding to its receptor induces receptor dimerization and activation of Janus kinase (JAK) tyrosine kinases. Activated JAKs phosphorylate specific tyrosine residues on the receptor, creating docking sites for STAT proteins. STAT proteins, upon phosphorylation, dimerize, translocate to the nucleus, and bind to DNA, regulating the transcription of genes involved in neutrophil development.
Elimination: Both filgrastim and pegfilgrastim are primarily eliminated through neutrophil-mediated clearance, a process where neutrophils themselves internalize and degrade the drug. Hepatic metabolism also contributes to elimination.
Dosage
Standard Dosage
Adults:
For chemotherapy-induced neutropenia, the recommended dose of filgrastim is 5 mcg/kg/day subcutaneously or intravenously. Pegfilgrastim, a long-acting form, is typically administered as a single dose of 6 mg subcutaneously once per chemotherapy cycle. The dosage and duration of treatment may vary based on the chemotherapy regimen and patient response.
Children:
Pediatric dosing of G-CSF is generally weight-based, similar to adult dosing (5 mcg/kg/day). Safety and efficacy in children have been established, but careful monitoring is necessary.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required based solely on age. However, close monitoring of renal and hepatic function is important.
- Patients with Renal Impairment: Dose adjustment is not usually necessary, but monitoring is essential.
- Patients with Hepatic Dysfunction: Dosage adjustments are not generally required, but caution is warranted.
- Patients with Comorbid Conditions: Careful consideration should be given to patients with pre-existing conditions, including sickle cell disorders, a history of splenic enlargement, or respiratory problems.
Clinical Use Cases
Dosage recommendations in specific clinical settings are based on established guidelines and protocols. These may vary based on the patient’s specific situation and the underlying medical condition being treated. Consult specialized guidelines for specific dosing recommendations.
Dosage Adjustments
Dosage modifications are based on patient factors such as ANC, renal/hepatic function, and tolerance. Close monitoring of blood counts and clinical response is essential for optimal dose titration.
Side Effects
Common Side Effects
Common side effects include bone pain, fever, fatigue, headache, and injection site reactions.
Rare but Serious Side Effects
Rare but serious side effects include splenic rupture, acute respiratory distress syndrome (ARDS), serious allergic reactions, and capillary leak syndrome.
Long-Term Effects
Long-term effects of G-CSF therapy are not well-established. Some studies suggest a potential increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients receiving chronic G-CSF therapy, particularly those with severe congenital neutropenia.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, splenic rupture, ARDS, and capillary leak syndrome. These require immediate medical attention.
Contraindications
G-CSF is contraindicated in patients with a history of serious allergic reactions to G-CSF products.
Drug Interactions
Lithium and other drugs that stimulate neutrophil release should be used with caution in patients receiving G-CSF, as they can potentiate the effects on white blood cell counts. G-CSF should not be administered within 24 hours before or after chemotherapy due to potential interactions with rapidly dividing myeloid cells.
Pregnancy and Breastfeeding
G-CSF should be used with caution during pregnancy. While limited data suggest that G-CSF is poorly excreted into breast milk, the potential risks to the infant are not fully understood. It is generally recommended that breastfeeding be interrupted during G-CSF therapy.
Drug Profile Summary
- Mechanism of Action: Stimulates neutrophil production and enhances neutrophil function.
- Side Effects: Bone pain, fever, fatigue, splenic rupture, ARDS, allergic reactions.
- Contraindications: History of serious allergic reactions to G-CSF products.
- Drug Interactions: Lithium, other neutrophil-stimulating drugs, chemotherapy.
- Pregnancy & Breastfeeding: Use with caution; breastfeeding interruption recommended.
- Dosage: 5 mcg/kg/day for filgrastim; 6 mg single dose per cycle for pegfilgrastim.
- Monitoring Parameters: Absolute neutrophil count (ANC), complete blood count (CBC), signs and symptoms of infection, splenic size.
Popular Combinations
G-CSF is often used in combination with chemotherapy regimens to mitigate neutropenia.
Precautions
General precautions involve monitoring blood counts, assessing for signs of infection, and evaluating splenic size. Specific precautions are warranted in pregnant women, breastfeeding mothers, and patients with pre-existing hematologic or respiratory disorders.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Granulocyte Colony Stimulating Factor?
A: The recommended dosage for filgrastim is 5 mcg/kg/day, and for pegfilgrastim, it is 6 mg subcutaneously once per chemotherapy cycle. Pediatric dosing is generally the same, but weight-based.
Q2: What are the common side effects of G-CSF?
A: Common side effects include bone pain, fever, fatigue, and injection site reactions.
Q3: Are there any serious side effects associated with G-CSF?
A: Yes, rare but serious side effects include splenic rupture, acute respiratory distress syndrome (ARDS), and severe allergic reactions.
Q4: Can G-CSF be used in pregnant women?
A: G-CSF should be used with caution during pregnancy. The potential risks to the fetus are not fully known.
Q5: Is it safe to breastfeed while taking G-CSF?
A: G-CSF is excreted in breast milk in small amounts. It is generally recommended to interrupt breastfeeding while receiving G-CSF.
Q6: How does G-CSF work in the body?
A: G-CSF binds to receptors on myeloid progenitor cells, stimulating neutrophil production and maturation in the bone marrow.
Q7: What are the contraindications for G-CSF use?
A: G-CSF is contraindicated in patients with a history of serious allergic reactions to G-CSF products.
Q8: What medications interact with G-CSF?
A: Lithium and other drugs that stimulate neutrophil release can interact with G-CSF. Chemotherapy agents also require careful timing of administration with G-CSF.
Q9: How is G-CSF administered?
A: G-CSF is administered either subcutaneously or intravenously.
Q10: What should be monitored in patients receiving G-CSF?
A: Monitor absolute neutrophil count (ANC), complete blood count (CBC), signs and symptoms of infection, and splenic size.
