NEUPOGEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEUPOGEN (NEUPOGEN).
Filgrastim is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. It acts by binding to G-CSF receptors on hematopoietic progenitor cells, stimulating proliferation, differentiation, and maturation of neutrophils.
| Metabolism | Filgrastim is primarily metabolized by neutrophils via receptor-mediated degradation and proteolysis. No significant hepatic metabolism by cytochrome P450 enzymes. |
| Excretion | Primarily renal; greater than 90% of filgrastim is eliminated via renal excretion as intact protein and degraded metabolites. Biliary/fecal excretion is minimal (<1%). |
| Half-life | 3.5 hours (range 2.5–4.5 hours) in healthy subjects; terminal elimination half-life is prolonged in patients receiving chemotherapy due to decreased clearance, approximately 5.5 hours. |
| Protein binding | Approximately 60% bound to serum albumin; binding is reversible and non-saturable at therapeutic concentrations. |
| Volume of Distribution | 0.5–1.5 L/kg; distributes primarily into blood and bone marrow. Lower Vd in neutropenic patients suggests restricted extravascular distribution. |
| Bioavailability | Subcutaneous: 62–89% (absolute bioavailability approximately 80%); intravenous: 100%. |
| Onset of Action | Subcutaneous: 1–2 hours for increase in neutrophil count; intravenous: within 2 hours. |
| Duration of Action | Neutrophil elevation persists for 4–7 days after cessation of therapy; bone marrow recovery may extend beyond this. |
| Action Class | Granulocyte-colony stimulating factor (G-CSF) |
| Brand Substitutes | Granfill 300mcg Injection, Neukine 300mcg Injection, Ancount Injection, Grafeel Injection, Imumax 300mcg Injection |
5 mcg/kg subcutaneously or intravenously once daily for up to 14 days, or until absolute neutrophil count reaches 10,000/mm³ after nadir. For mobilization of peripheral blood progenitor cells: 10 mcg/kg subcutaneously once daily for 6-7 days.
| Dosage form | SYRINGE |
| Renal impairment | Not required; no dose adjustment necessary based on GFR as drug is renally cleared but dose adjustments are not recommended per FDA labeling. |
| Liver impairment | No formal Child-Pugh based dose adjustments established; use with caution in severe hepatic impairment. |
| Pediatric use | For chemotherapy-induced neutropenia: 5 mcg/kg subcutaneously or intravenously once daily for up to 14 days. For severe chronic neutropenia: 6 mcg/kg subcutaneously twice daily. Dosing based on actual body weight; no maximum weight cap specified. |
| Geriatric use | No specific dose adjustments; use same dosing as younger adults, but monitor for increased adverse effects (e.g., bone pain, splenic rupture) due to potential age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEUPOGEN (NEUPOGEN).
| Breastfeeding | It is not known whether filgrastim is excreted in human milk; however, due to its high molecular weight (18.8 kDa), it is likely minimally excreted. No M/P (milk-to-plasma) ratio is available. The American Academy of Pediatrics considers filgrastim to be compatible with breastfeeding. Caution should be exercised, and the nursing infant should be monitored for potential adverse effects such as neutropenia or thrombocytopenia. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, filgrastim (Neupogen) has been shown to have adverse effects on fetal development, including increased rates of spontaneous abortion, fetal malformations, and decreased fetal weight. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited human data suggest no increased risk of major congenital anomalies; however, first trimester exposure is associated with a possible increase in preterm delivery and low birth weight. Second and third trimester exposure may be associated with transient maternal neutropenia. |
■ FDA Black Box Warning
Filgrastim should not be used to increase the dose of chemotherapy beyond established dose regimens. There is a risk of acute respiratory distress syndrome (ARDS) in patients receiving filgrastim and chemotherapy. Allergic reactions, including anaphylaxis, have been reported.
| Serious Effects |
["Hypersensitivity to filgrastim or any product component","Do not use concurrently with chemotherapy or radiation therapy (24-hour interval recommended)"]
| Precautions | ["Splenic rupture: Monitor for left upper quadrant pain or shoulder tip pain","Acute respiratory distress syndrome (ARDS): Evaluate patients with fever and respiratory distress","Allergic reactions: Discontinue if severe allergic reaction occurs","Sickle cell crisis: Use caution in patients with sickle cell disease","Leukocytosis: Monitor white blood cell count","Capillary leak syndrome: Monitor for hypotension, edema, and hemoconcentration"] |
Loading safety data…
| Fetal Monitoring | Maternal monitoring: Complete blood count (CBC) with differential and platelet count should be monitored regularly, particularly during the first few weeks of therapy and after dose adjustments. Monitor for signs of infection, splenic rupture (left upper quadrant pain, shoulder tip pain), respiratory distress syndrome, and allergic reactions. Fetal monitoring: Ultrasound for fetal growth and development if used during pregnancy; assessment for signs of transient neutropenia in the newborn if used near term. |
| Fertility Effects | Filgrastim has been shown to increase the likelihood of conception in some animal studies due to its role in follicular development and ovulation. However, there are no controlled human studies on fertility. Potential effects on spermatogenesis or ovarian function are not well characterized. In patients undergoing chemotherapy, filgrastim may improve reproductive outcomes by reducing myelosuppression, but direct fertility effects are not established. |