Should I give Neupogen (filgrastim) to a patient with malignancy admitted for infection and found to have neutropenia?

Management of Neutropenia in Patients with Malignancy and Infection

For a patient with malignancy admitted for infection and found to have neutropenia, filgrastim (Neupogen) should be administered if the neutrophil count is <0.5 × 10^9/L, especially if there are risk factors for poor outcomes such as severe neutropenia, sepsis, or prolonged expected neutropenia.

Assessment of Neutropenia Severity and Risk

• Febrile neutropenia is defined as a temperature >38.5°C for more than 1 hour with an absolute neutrophil count (ANC) <0.5 × 10^9/L 1
• Risk factors for infection-related complications or poor clinical outcome include:
  • Age >65 years 1, 2
  • Sepsis syndrome 1
  • Severe neutropenia (ANC <100/μL) 1
  • Anticipated prolonged neutropenia (>10 days) 1
  • Pneumonia or invasive fungal infection 1
  • Previous episodes of neutropenia 2

Treatment Recommendations

• For established neutropenia with infection, filgrastim is preferred over pegfilgrastim due to its shorter half-life and ability to titrate the dose 3, 4
• Standard filgrastim dosing is 5 μg/kg/day subcutaneously until neutrophil recovery to normal or near-normal levels 1, 3
• Begin filgrastim administration within 24 hours of antibiotic initiation for better outcomes 5
• Continue treatment until sufficient/stable post-nadir ANC recovery (achieving a target ANC of >10 × 10^9/L is not necessary) 1
• The dose may be rounded to the nearest vial size according to institution-defined weight limits 1

Evidence for Efficacy

• Filgrastim treatment used with antibiotics at the onset of febrile neutropenia accelerates neutrophil recovery and shortens the duration of febrile neutropenia 5
• In patients with established febrile neutropenia, filgrastim reduces the median number of days of neutropenia (3.0 compared with 4.0 days with placebo) 5
• Filgrastim decreases the risk for prolonged hospitalization by half in patients with febrile neutropenia 5
• The greatest benefit appears to be in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 × 10^9/L 5

Contraindications and Precautions

• Colony-stimulating growth factors should not be used in patients without neutropenia suffering from community- or hospital-acquired pneumonitis 1
• Filgrastim is contraindicated during radiotherapy to the chest due to increased rate of complications and death 1
• There is a risk of worsening thrombocytopenia when hematopoietic growth factors are given immediately prior to or simultaneously with chemotherapy 1

Monitoring

• Monitor complete blood count with differential regularly to assess response to therapy 6
• No specific ECG monitoring is required during filgrastim administration, though a reduction in mean heart rate may occur 7
• Continue treatment until ANC recovery, typically for 5-7 days 6

Clinical Pitfalls to Avoid

• Avoid delaying filgrastim administration in patients with severe neutropenia (ANC <100/μL) as they derive the greatest benefit 5
• Do not use pegfilgrastim for treatment of established neutropenia due to its long half-life and inability to adjust dosing 3, 4
• Do not continue filgrastim unnecessarily once neutrophil count has recovered, as achieving an ANC >10 × 10^9/L is not necessary 1
• Do not administer filgrastim simultaneously with chemotherapy due to risk of severe thrombocytopenia 1