What are the indications and recommended dosing for filgrastim (recombinant human granulocyte‑colon stimulating factor)?

Filgrastim: Indications and Dosing

Primary Indications

Filgrastim is indicated for prevention of chemotherapy-induced febrile neutropenia, mobilization of peripheral blood progenitor cells, treatment of severe chronic neutropenia, and management of acute radiation syndrome. 1

1. Chemotherapy-Induced Neutropenia Prevention (Primary Prophylaxis)

• Use when the risk of febrile neutropenia is ≥20% based on the chemotherapy regimen or when patient-specific risk factors (age >65 years, prior chemotherapy, poor performance status, pre-existing neutropenia) elevate baseline risk. 1
• Prophylaxis is particularly important in patients receiving curative-intent therapy where maintaining dose intensity is critical for outcomes. 1
• Do not use prophylactically during concurrent chemotherapy and radiation therapy, especially involving the mediastinum, due to increased complications and mortality risk. 1, 2

2. Peripheral Blood Progenitor Cell (PBPC) Mobilization

• Indicated for mobilizing stem cells for autologous or allogeneic transplantation. 1
• Also used for mobilizing granulocytes for transfusion in allogeneic donors. 1

3. Severe Chronic Neutropenia

• Indicated for congenital neutropenia, cyclic neutropenia, and idiopathic neutropenia with recurrent infections and absolute neutrophil count (ANC) <500/mm³. 3, 4

4. Acute Radiation Syndrome

• Approved for patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome). 3

5. Post-Transplant Neutrophil Recovery

• Used after autologous stem cell or cord blood transplantation to accelerate neutrophil recovery. 1

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Standard Dosing Regimens

Chemotherapy-Induced Neutropenia (Prophylaxis)

Dose: 5 mcg/kg/day subcutaneously 1, 2

• Timing: Start 24-72 hours (1-3 days) after completion of chemotherapy. 1, 2
• Never administer on the same day as chemotherapy or within 24 hours before chemotherapy, as this increases febrile neutropenia rates and adverse events by pushing cells into the cell cycle when most vulnerable to chemotherapeutic killing. 1, 2, 5
• Duration: Continue daily until ANC recovers to 2,000-3,000 cells/µL (2-3 × 10⁹/L), typically 7-14 days per cycle. 1, 2
• Restart with each subsequent chemotherapy cycle; prophylaxis must continue through all cycles, not just the first few. 2, 5
• Doses may be rounded to the nearest vial size (e.g., 300 mcg or 480 mcg) according to institutional protocols while maintaining therapeutic levels. 1, 2, 5

For a typical 70 kg adult, this translates to 350 mcg daily—fixed low doses like 60 mcg are inadequate and not supported by evidence. 5

High-Dose Chemotherapy and Stem Cell Rescue

Dose: 5 mcg/kg/day subcutaneously 1, 3

• Timing: Start 24-120 hours (1-5 days) after high-dose therapy or stem cell infusion. 1, 2, 3
• Duration: Continue until ANC recovers to normal or near-normal levels. 1, 2
• Post-autologous transplant, begin on day +5 and continue until ANC >1.5 × 10⁹/L for 2 consecutive days. 1

PBPC Mobilization

Dose: 10 mcg/kg/day subcutaneously (higher than standard prophylaxis dose) 1

• Timing: Start at least 4 days before the first leukapheresis procedure. 1, 2
• Duration: Continue through the last leukapheresis session. 1
• For allogeneic donors, use 10 mcg/kg/day starting 4-5 days before collection. 1
• For granulocyte transfusion donors, give one dose of 5 mcg/kg with dexamethasone 10 mg PO 8-24 hours before collection. 1

Severe Chronic Neutropenia

Initial dosing varies by diagnosis: 3, 4

• Idiopathic neutropenia: 3.6 mcg/kg/day subcutaneously 3
• Cyclic neutropenia: 6 mcg/kg/day subcutaneously 3
• Congenital neutropenia: 6 mcg/kg/day divided twice daily 3
• Dose escalation: Increase incrementally up to 12 mcg/kg/day divided twice daily if no response. 3
• Duration: Continue long-term with dose adjustments to maintain target ANC (typically >1,500/mm³ for complete response or 500-1,500/mm³ for partial response). 2, 5, 3

Acute Radiation Syndrome

Dose: 10 mcg/kg/day subcutaneously 3

• Timing: Start as soon as possible after radiation exposure. 3
• Duration: Continue until ANC ≥1,000/mm³ for 3 consecutive days, or ANC ≥10,000/mm³ for >2 consecutive days within days 1-5, or ANC ≥10,000/mm³ any time after day 5. 3

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Route of Administration

Subcutaneous injection is the preferred route for all indications due to better tolerability and convenience. 1

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Pegfilgrastim as an Alternative

Pegfilgrastim (pegylated G-CSF) offers once-per-cycle dosing as an alternative to daily filgrastim for chemotherapy-induced neutropenia prophylaxis. 1, 6

Pegfilgrastim Dosing

• Fixed dose: 6 mg subcutaneously once per chemotherapy cycle 1, 6
• Timing: Administer 24 hours (1-3 days) after completion of chemotherapy. 1, 6
• For patients <45 kg: Use weight-based dosing of 100 mcg/kg instead of the fixed 6 mg dose. 1, 6
• Not indicated for: stem cell mobilization, weekly chemotherapy regimens, cycles shorter than 2-3 weeks, or therapeutic use in established febrile neutropenia. 1, 6

Comparative Efficacy

• Pegfilgrastim and filgrastim are therapeutically equivalent for preventing febrile neutropenia; choice depends on convenience, cost, and clinical scenario. 1, 6
• A 2011 meta-analysis showed pegfilgrastim reduced febrile neutropenia risk more than filgrastim (RR 0.66; 95% CI 0.44-0.98), though both significantly lower risk versus no growth factor. 1, 6
• Prefer pegfilgrastim for standard 3-week chemotherapy cycles when convenience is prioritized; prefer filgrastim for weekly chemotherapy, short-interval cycles, or when dose titration is needed. 6

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Critical Timing and Safety Considerations

Timing Pitfalls

• Same-day administration with chemotherapy increases febrile neutropenia rates and adverse events in breast cancer and lymphoma patients. 1, 2, 6, 5
• Administering filgrastim during active chemotherapy pushes cells into the cell cycle when most susceptible to chemotherapeutic killing. 2, 5
• The 24-72 hour delay after chemotherapy is mandatory, not optional. 1, 2

Contraindications and Warnings

• Avoid concurrent use with chemotherapy and radiation therapy, particularly mediastinal radiation, due to increased mortality risk. 1, 2, 5
• Do not use pegfilgrastim therapeutically for established febrile neutropenia; filgrastim's shorter half-life allows dose titration. 6
• In pediatric acute lymphoblastic leukemia (ALL), use cautiously due to potential increased risk of therapy-related myeloid leukemia or myelodysplastic syndrome, especially with concurrent irradiation, topoisomerase II inhibitors, or alkylating agents. 1

Common Adverse Effects

• Bone pain, arthralgias, and myalgias are the most common side effects, manageable with NSAIDs. 6
• Asymptomatic splenic enlargement occurs frequently in severe chronic neutropenia patients. 4
• Headache and rash are generally mild and easily manageable. 4

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Biosimilars

Filgrastim-sndz and tbo-filgrastim are FDA-approved biosimilars with equivalent efficacy and safety to reference filgrastim. 1

• Tbo-filgrastim showed no statistically significant difference in first-cycle febrile neutropenia rates compared to filgrastim (adjusted difference 1.7%; 95% CI -3.8% to 7.1%). 1
• Filgrastim-sndz demonstrated noninferiority to filgrastim in duration of severe neutropenia after cycle one chemotherapy in breast cancer patients. 1
• Biosimilars can reduce cost barriers while maintaining therapeutic equivalence. 6

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Special Populations

Pediatric Patients

• The 6 mg pegfilgrastim prefilled syringe should not be used in children weighing <45 kg; use weight-based dosing (100 mcg/kg) instead. 1, 6
• Filgrastim use in pediatric patients is typically guided by clinical protocols. 1

Older Adults (≥65 Years)

• Prophylactic filgrastim is recommended for patients ≥65 years with lymphoma receiving curative chemotherapy (CHOP or more aggressive regimens) to reduce febrile neutropenia and infection incidence. 1
• Age >65 years is an independent risk factor elevating baseline febrile neutropenia risk. 6