Pegfilgrastim [Pegylated Filgrastim]

Approved Indications:

• Prevention of Febrile Neutropenia in Chemotherapy:
  Indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant risk of neutropenia.
• Acute Radiation Syndrome (Hematopoietic Subsyndrome):
  Approved to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Clinically Accepted Off-label Uses:

• Mobilization of Hematopoietic Progenitor Cells for Stem Cell Transplantation:
  Used in protocols for autologous peripheral blood stem cell mobilization in oncology settings.
• Supportive Therapy in Bone Marrow Transplant Patients:
  Occasionally used post-transplant to accelerate neutrophil recovery, although not FDA-labeled for this use.

Route of Administration: Subcutaneous (SC) injection only
Available Formulations: Prefilled syringe (6 mg/0.6 mL)

Adults:

• Prevention of Febrile Neutropenia:
• Dose: 6 mg SC once per chemotherapy cycle
• Timing: Administer at least 24 hours after and not within 14 days before the next cycle of chemotherapy
• Radiation-Induced Myelosuppression:
• Dose: Two doses of 6 mg SC, administered 1 week apart
• Weight-based option for pediatrics: See below

Pediatrics (for Radiation Syndrome):

• <45 kg: Weight-based dosing at 0.1 mg/kg SC once per week for 2 doses
• ≥45 kg: Fixed dose of 6 mg SC once per week for 2 doses

Elderly Patients:

• No dosage adjustment required based on age. Monitor for increased sensitivity to adverse effects.

Renal or Hepatic Impairment:

• No dosage adjustment required. Use cautiously as clinical experience is limited in severe organ dysfunction.

Administration Notes:

• Administer SC in the abdomen, thigh, or upper arm.
• Rotate injection sites.
• Avoid shaking the syringe to prevent protein denaturation.
• Pegfilgrastim is not for IV use.
• Do not administer on the same day as chemotherapy.

Pegfilgrastim is a pegylated form of filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF). It binds to specific cell surface receptors on hematopoietic progenitor cells and stimulates proliferation, differentiation, and activation of neutrophil precursors. Pegylation extends the half-life and duration of action by reducing renal clearance. The result is an increase in neutrophil production and function, helping to restore neutrophil counts in patients with chemotherapy-induced neutropenia or bone marrow suppression.

• Absorption: Complete absorption after SC injection; peak concentrations within 16–120 hours depending on neutrophil-mediated clearance
• Distribution: Volume of distribution is small (~170 mL/kg), confined primarily to extracellular fluid
• Metabolism: Metabolized by neutrophil-mediated clearance and renal elimination; not metabolized by CYP enzymes
• Elimination: Clearance decreases as neutrophil counts fall; cleared more rapidly when neutrophils are abundant
• Half-life: Variable, depending on neutrophil count; typically 15–80 hours (longer than filgrastim)
• Bioavailability: Near complete after SC administration

• Pregnancy:
  FDA Pregnancy Category C (previous classification). Animal studies showed potential fetal harm, but no well-controlled human data are available. Should be used in pregnancy only if clearly needed and if potential benefits justify potential risks.
• Lactation:
  Unknown whether pegfilgrastim is excreted in human milk. Use caution in breastfeeding women. Because of potential effects on rapidly dividing cells, it is advised to weigh the benefits of treatment against potential infant risk.

• Primary Class: Hematopoietic Agent
• Subclass: Long-acting Granulocyte Colony-Stimulating Factor (G-CSF)
• Form: Pegylated recombinant human G-CSF

• Known hypersensitivity to pegfilgrastim, filgrastim, or any excipients in the formulation
• History of serious allergic reactions to human G-CSF products
• Concurrent use with chemotherapy or within 14 days before next cycle
• Neonates or pediatric patients weighing <10 kg for standard fixed-dose formulation

• Splenic Rupture: May present with left upper abdominal or shoulder pain; rare but potentially fatal
• Acute Respiratory Distress Syndrome (ARDS): Can occur in neutropenic patients with sepsis or pneumonia
• Allergic Reactions: Serious hypersensitivity reactions including anaphylaxis may occur
• Leukocytosis: Excessive neutrophil counts may occur; monitor white blood cell counts
• Myelodysplastic Syndrome (MDS)/AML Risk: In patients with breast or lung cancer receiving growth factor support, a small increased risk of secondary hematologic malignancy has been observed
• Capillary Leak Syndrome: Rare, potentially fatal condition with hypotension and edema
• Tumor Growth Stimulation: G-CSF receptors on certain tumors may theoretically accelerate tumor growth
• Sickle Cell Disease: May trigger sickle cell crises; use cautiously

Common Side Effects:

• Musculoskeletal: Bone pain, myalgia, back pain, arthralgia
• General: Fatigue, headache, injection site discomfort
• Gastrointestinal: Nausea, diarrhea
• Hematologic: Elevated white blood cell count (leukocytosis)

Serious or Rare Side Effects:

• Splenic rupture
• Anaphylaxis and severe allergic reactions
• Acute respiratory distress syndrome (ARDS)
• Capillary leak syndrome
• Sickle cell crisis in susceptible patients
• Cutaneous vasculitis
• Aortitis (inflammation of the aorta)

Timing of Onset:
Bone pain often occurs within 1–2 days of administration. Serious effects are rare but may present early in the treatment cycle.

• Cytotoxic Chemotherapy: Pegfilgrastim should not be given within 24 hours before or after chemotherapy due to potential interaction with chemotherapy-induced bone marrow suppression.
• No Known CYP450 Interactions: Not metabolized by cytochrome enzymes; unlikely to interfere with CYP substrates, inducers, or inhibitors.
• Immunomodulators: No formal studies, but caution advised when used with other immune-regulating agents.
• Radiation Therapy: Use in radiation-induced myelosuppression is supported but not combined with cytotoxic drugs.

• FDA Labeling Update: The FDA recently updated the label to clarify dosing in pediatric patients exposed to radiation and to highlight risks of aortitis and splenic rupture more prominently.
• ASCO/ESMO Guidelines (2024): Pegfilgrastim remains first-line for prevention of febrile neutropenia in patients on high-risk chemotherapy protocols.
• EMA Guidance: Supports once-per-cycle use of pegfilgrastim over daily filgrastim due to improved compliance and similar outcomes.
• Biosimilars: Several pegfilgrastim biosimilars (e.g., pegfilgrastim-jmdb, pegfilgrastim-cbqv) have been approved and are interchangeable with the reference product.

• Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
• Avoid Freezing: If frozen, discard. Do not shake the syringe.
• Light Protection: Keep in the original carton to protect from light
• Room Temperature Stability: May be stored at room temperature (maximum 30°C) for up to 72 hours. If removed from refrigeration and not used within this time, discard
• Handling Precautions: Do not use if the solution is cloudy or discolored. Do not reuse syringes.