Usage
Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog, a recombinant human protein that stimulates the production and function of neutrophils (a type of white blood cell crucial for fighting infections). It falls under the pharmacological classification of immunostimulants, specifically, colony-stimulating factors.
Filgrastim is prescribed for various medical conditions, including:
- Neutropenia: Reducing the duration of neutropenia (low neutrophil count) and the incidence of febrile neutropenia (fever associated with neutropenia) in patients undergoing chemotherapy, bone marrow transplantation, or suffering from congenital, cyclic, or idiopathic neutropenia.
- Peripheral Blood Progenitor Cell (PBPC) Mobilization: Increasing the number of PBPCs in the bloodstream, facilitating collection for transplantation.
- Severe Chronic Neutropenia (SCN): Long-term administration to increase neutrophil counts and reduce infection risk.
- HIV Infection: Treating persistent neutropenia in patients with advanced HIV infection to lower the risk of bacterial infections.
- Acute Radiation Syndrome: Increasing survival in patients exposed to myelosuppressive doses of radiation.
Filgrastim’s mechanism of action involves binding to specific receptors on the surface of neutrophil precursor cells in the bone marrow, stimulating their growth, differentiation, and release into the bloodstream. This leads to a significant increase in the number of circulating neutrophils, bolstering the body’s ability to combat infections.
Alternate Names
Filgrastim is also known as granulocyte colony-stimulating factor (G-CSF). Some popular brand names under which it is marketed include Neupogen, Zarzio, Nivestym, and Granix.
How It Works
Pharmacodynamics: Filgrastim exerts its primary effect by binding to G-CSF receptors on hematopoietic progenitor cells in the bone marrow. This binding triggers intracellular signaling pathways, promoting proliferation, differentiation, and activation of neutrophils. The increase in neutrophil count leads to enhanced immune function and improved resistance to infections.
Pharmacokinetics: Filgrastim is administered subcutaneously or intravenously. Subcutaneous administration results in slower absorption compared to intravenous administration. It is primarily eliminated through neutrophil-mediated clearance. The half-life of filgrastim is variable, depending on the dose and neutrophil count, typically ranging from 1 to 8 hours. No significant accumulation occurs with repeated dosing. Dose adjustments are not typically required in patients with renal or hepatic impairment.
Dosage
Standard Dosage
Adults:
The standard starting dose for adults is 5 mcg/kg/day administered subcutaneously, as a short intravenous infusion (15-30 minutes), or as a continuous intravenous infusion. The dosage may be adjusted based on the patient’s response and the specific indication.
Children:
Pediatric dosing is generally weight-based, similar to adult dosing (5 mcg/kg/day). For SCN, higher doses and divided dosing may be necessary.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically recommended for elderly patients.
- Patients with Renal Impairment: No dose adjustments are typically needed.
- Patients with Hepatic Dysfunction: No dose adjustments are typically needed.
- Patients with Comorbid Conditions: Consider individual patient factors and adjust dosage as needed.
Clinical Use Cases
Dosage recommendations vary based on the clinical context. In all scenarios, consider renal and hepatic function as well as concomitant medications that may potentiate or inhibit filgrastim’s effects. Specific dosage guidance for intubation, surgical procedures, mechanical ventilation, intensive care unit use, and emergency situations such as cardiac arrest is not provided.
Dosage Adjustments
Dose adjustments are based on the absolute neutrophil count (ANC) and the patient’s clinical response. Dose escalation or reduction may be necessary to achieve and maintain the desired neutrophil count.
Side Effects
Common Side Effects:
The most common side effect is mild to moderate bone pain, often managed with analgesics. Other common side effects include fever, headache, fatigue, and rash.
Rare but Serious Side Effects:
Rare but serious side effects include splenomegaly (enlarged spleen) with potential for rupture, acute respiratory distress syndrome (ARDS), allergic reactions, and aortitis.
Long-Term Effects:
Long-term use may be associated with a decreased bone density in some patients, especially children with SCN.
Contraindications
Filgrastim is contraindicated in patients with a history of serious allergic reactions to filgrastim, pegfilgrastim, or any components of the product, including E. coli-derived proteins. Caution should be exercised in patients with sickle cell disease as filgrastim may precipitate a sickle cell crisis.
Drug Interactions
Filgrastim may interact with lithium and other drugs that can stimulate neutrophil production, potentially leading to additive effects. Concomitant use with cytotoxic chemotherapy should be carefully managed. Filgrastim should not be administered 24 hours before or after cytotoxic chemotherapy.
Pregnancy and Breastfeeding
Filgrastim is classified as Pregnancy Category C. It should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is not known whether filgrastim is excreted in human milk. Due to potential risks to the infant, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Stimulates neutrophil production by binding to G-CSF receptors.
- Side Effects: Bone pain, fever, headache, fatigue, rash; rarely, splenic rupture, ARDS, allergic reactions.
- Contraindications: Hypersensitivity to filgrastim, pegfilgrastim, or E. coli-derived proteins.
- Drug Interactions: Lithium, cytotoxic chemotherapy.
- Pregnancy & Breastfeeding: Category C; use with caution; unknown if excreted in breast milk.
- Dosage: 5 mcg/kg/day, adjusted based on ANC response.
- Monitoring Parameters: Absolute neutrophil count (ANC), complete blood count (CBC), signs and symptoms of infection.
Popular Combinations
Filgrastim is often used in combination with chemotherapy regimens to mitigate the neutropenic effects of chemotherapy.
Precautions
Monitor patients for common side effects such as bone pain. Closely observe for signs of splenomegaly. Patients with sickle cell disease should be monitored for signs of sickle cell crisis. Monitor ANC and CBC regularly during treatment. Educate patients about potential side effects and when to seek medical attention.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Filgrastim?
A: The standard adult starting dose is 5 mcg/kg/day, adjustable based on the ANC response. Pediatric dosing is similar, often weight-based.
Q2: What is the most common side effect of Filgrastim?
A: Bone pain is the most frequently reported side effect, usually mild to moderate and manageable with analgesics.
Q3: How is Filgrastim administered?
A: Filgrastim can be administered subcutaneously or intravenously, either as a short infusion or continuous infusion.
Q4: What are the contraindications to Filgrastim?
A: Known hypersensitivity to filgrastim, pegfilgrastim, or components of the product (including E. coli-derived proteins) contraindicates its use.
Q5: Can Filgrastim be used during pregnancy?
A: Filgrastim is a Pregnancy Category C drug. It should only be used if the potential benefit justifies the potential risk to the fetus.
Q6: What should be monitored during Filgrastim treatment?
A: Absolute neutrophil count (ANC), complete blood count (CBC), and any signs and symptoms of infection should be closely monitored.
Q7: What are the rare but serious side effects of Filgrastim?
A: Splenic rupture, acute respiratory distress syndrome (ARDS), and severe allergic reactions are rare but serious potential side effects.
Q8: How does Filgrastim work in the body?
A: Filgrastim binds to G-CSF receptors, stimulating the production, differentiation, and activation of neutrophils in the bone marrow.
Q9: Can Filgrastim be used in patients with renal or hepatic impairment?
A: Dose adjustments are typically not required for patients with renal or hepatic dysfunction.
Q10: What are the potential drug interactions with Filgrastim?
A: Lithium and other drugs that stimulate neutrophil production can interact with Filgrastim. Cytotoxic chemotherapy requires careful management when used concurrently with Filgrastim.
