NEULASTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEULASTA (NEULASTA).
Pegfilgrastim is a recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) conjugated to polyethylene glycol. It binds to G-CSF receptors on hematopoietic progenitor cells, stimulating proliferation, differentiation, and release of neutrophils from the bone marrow.
| Metabolism | Primarily cleared by neutrophil-mediated endocytosis and degradation; renal excretion plays a minor role. No significant hepatic metabolism. |
| Excretion | Primarily renal clearance (through glomerular filtration and proteolytic degradation). Approximately 80% of the dose is eliminated renally as degraded peptides. |
| Half-life | Terminal elimination half-life is approximately 15-23 hours (mean ~18 hours) in healthy subjects, allowing for once-per-cycle dosing for chemotherapy-induced neutropenia. |
| Protein binding | Filgrastim (the active ingredient) is primarily bound to serum albumin and other proteins; binding is approximately 70-90%. |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is approximately 150 mL/kg (0.15 L/kg), indicating distribution primarily within the vascular and extracellular fluid spaces. |
| Bioavailability | Subcutaneous administration: absolute bioavailability is approximately 60-70% compared to intravenous administration. |
| Onset of Action | Subcutaneous administration: increases in absolute neutrophil count (ANC) are observed within 24 hours, with peak ANC elevation occurring around 24-72 hours post-dose. |
| Duration of Action | Duration of ANC elevation lasts approximately 7-10 days, sufficient to cover the typical neutropenic nadir after myelosuppressive chemotherapy. Single dose per cycle is effective. |
6 mg subcutaneously once per chemotherapy cycle, administered at least 24 hours after cytotoxic chemotherapy and at least 14 days before next cycle.
| Dosage form | SYRINGE |
| Renal impairment | No dose adjustment required for renal impairment, including end-stage renal disease. |
| Liver impairment | No dose adjustment required for hepatic impairment; not studied in Child-Pugh class C. |
| Pediatric use | Dosing for pediatric patients based on body weight: 100 mcg/kg as a single subcutaneous injection; no dose established for patients <45 kg (use 6 mg fixed dose for ≥45 kg after chemotherapy). |
| Geriatric use | No dose adjustment required based on age; similar safety and efficacy observed in patients ≥65 years as in younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEULASTA (NEULASTA).
| Breastfeeding | No data on presence in human milk; due to large molecular weight (PEGylated protein), transfer is likely low. Caution advised; M/P ratio not established. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of fetal harm. Risk cannot be ruled out; use only if clearly needed. No documented teratogenicity in first trimester. |
| Fetal Monitoring |
■ FDA Black Box Warning
None officially required by FDA.
| Serious Effects |
["History of serious allergic reactions to pegfilgrastim or filgrastim.","Hypersensitivity to E. coli-derived proteins."]
| Precautions | ["Splenic rupture (rare but serious).","Acute respiratory distress syndrome (ARDS).","Allergic reactions including anaphylaxis.","Sickle cell crisis in patients with sickle cell disorders.","Glomerulonephritis.","Leukocytosis.","Capillary leak syndrome.","Potential for tumor growth stimulation (theoretical).","Aortitis.","Increased risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer when used with chemotherapy and radiation."] |
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| Monitor complete blood count (CBC) with white cell differential during pregnancy. Assess for bone pain and splenic rupture symptoms. No specific fetal monitoring required beyond routine. |
| Fertility Effects | No evidence of impaired fertility in animal studies. Human data absent; theoretical potential for ovarian suppression with prolonged neutropenia. |