Filgrastim (Neupogen)

Overview

Filgrastim (Neupogen) is a recombinant human granulocyte colony-stimulating factor (G-CSF) that stimulates the bone marrow to produce neutrophils, a type of white blood cell essential for fighting bacterial infections. It is one of the most commonly used supportive care medications in oncology.

Key Features

• First-in-class hematopoietic growth factor (FDA approved 1991)
• Stimulates rapid neutrophil production
• Reduces risk of febrile neutropenia by approximately 50%
• Allows maintenance of chemotherapy dose intensity
• Can be self-administered at home
• Short-acting - requires daily injections
• Available in multiple biosimilar forms
• NOT a cancer treatment - supportive care only

What Filgrastim Does

• Stimulates bone marrow: Prompts production of neutrophils
• Shortens recovery time: Helps neutrophil counts recover faster after chemotherapy
• Reduces infection risk: Maintains adequate neutrophil levels to fight bacteria
• Prevents treatment delays: Allows chemotherapy to continue on schedule
• Maintains dose intensity: Enables full chemotherapy doses without reduction

What Filgrastim Does NOT Do

• Does NOT treat cancer: Has no direct anti-cancer effect
• Does NOT treat existing infections: Not an antibiotic or anti-infective
• Does NOT prevent all infections: Reduces risk but doesn't eliminate it
• Does NOT help other blood cells: Only affects neutrophils (not red blood cells or platelets)
• Does NOT reduce chemotherapy side effects: Only helps with neutropenia

Mechanism of Action

Filgrastim is a recombinant form of human granulocyte colony-stimulating factor (G-CSF), a naturally occurring protein that regulates neutrophil production.

How Filgrastim Works

1. Binds to G-CSF Receptors: Filgrastim binds to G-CSF receptors on bone marrow precursor cells
2. Stimulates Proliferation: Activates signaling pathways that promote proliferation of neutrophil precursors
3. Accelerates Maturation: Speeds up differentiation of precursor cells into mature neutrophils
4. Enhances Function: Improves function of mature neutrophils (phagocytosis, killing capacity)
5. Mobilizes Release: Causes rapid release of neutrophils from bone marrow into bloodstream
6. Extends Survival: Prolongs survival of circulating neutrophils

Pharmacokinetics

• Route: Subcutaneous (SC) or intravenous (IV) - SC most common
• Absorption: Well absorbed subcutaneously
• Peak levels: 2-8 hours after SC injection
• Half-life: 3.5 hours (short - requires daily dosing)
• Elimination: Cleared by neutrophil-mediated mechanisms (unique clearance)
• Effect on ANC: Typically increases within 24 hours, continues rising with daily doses
• Recovery after stopping: ANC usually returns to baseline within 4 days

Understanding the Bone Marrow Response

• Rapid effect: Neutrophil count starts rising within 24 hours
• Continued benefit: Daily administration maintains elevated counts
• Dose-dependent: Higher doses produce greater neutrophil increases
• Reversible: Effect resolves within days of stopping

FDA-Approved Indications

1. Chemotherapy-Induced Neutropenia

• Primary indication: Decrease incidence of infection (febrile neutropenia) in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy
• Most common use in clinical practice
• Eligible patients: Those receiving regimens with high (>20%) or intermediate (10-20%) risk of febrile neutropenia
• Benefit: Reduces febrile neutropenia risk by approximately 50%

2. Acute Myeloid Leukemia (AML)

• Indication: Reduce duration of neutropenia and neutropenia-related complications in adults with AML receiving induction or consolidation chemotherapy
• Timing: Started at least 24 hours after completion of cytotoxic chemotherapy

3. Bone Marrow Transplantation

• Indication: Reduce duration of neutropenia and neutropenia-related sequelae in patients undergoing myeloablative chemotherapy followed by bone marrow transplant
• Used in both autologous and allogeneic transplants

4. Peripheral Blood Progenitor Cell Collection

• Indication: Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis
• Use: Before autologous stem cell transplantation
• Dosing: Higher doses (10 mcg/kg) for mobilization

5. Severe Chronic Neutropenia

• Types: Congenital neutropenia, cyclic neutropenia, idiopathic neutropenia
• Goal: Reduce incidence and duration of infections
• Long-term use often required

6. Hematopoietic Syndrome of Acute Radiation Syndrome

• Indication: Increase survival in patients acutely exposed to myelosuppressive doses of radiation
• Rare use - emergency situations

Off-Label Uses

• HIV-associated neutropenia
• Drug-induced neutropenia (non-chemotherapy)
• Myelodysplastic syndrome (MDS): Selected patients with neutropenia and recurrent infections

Understanding Neutropenia

What is Neutropenia?

Neutropenia is an abnormally low number of neutrophils in the blood. Neutrophils are the most abundant type of white blood cell and are critical for fighting bacterial infections.

Neutropenia Severity Grading

Febrile Neutropenia

When Does Neutropenia Occur After Chemotherapy?

• Onset: Typically 7-14 days after chemotherapy
• Nadir: Lowest point usually day 10-14
• Recovery: Usually by day 21-28 (depending on regimen)
• Filgrastim's role: Shortens duration and severity of neutropenia

Risk Factors for Febrile Neutropenia

• Chemotherapy-related:
  • Highly myelosuppressive regimens
  • High chemotherapy dose intensity
  • Prolonged neutropenia (>7 days)
• Patient-related:
  • Age ≥65 years
  • Poor performance status
  • Previous febrile neutropenia
  • No prophylactic G-CSF use
  • Advanced cancer
  • Pre-existing neutropenia
  • Open wounds or recent surgery
  • Poor nutritional status
  • Extensive prior chemotherapy

Clinical Guidelines for G-CSF Use

Primary Prophylaxis (Before Any Neutropenia Occurs)

Secondary Prophylaxis (After Episode of Febrile Neutropenia)

• Indication: If patient had febrile neutropenia in previous cycle
• Recommendation: Use G-CSF in all subsequent cycles
• Rationale: Risk of recurrent FN is 50-60% without G-CSF
• Alternative: Chemotherapy dose reduction (less preferred if curative intent)

Dose-Dense Chemotherapy Regimens

• Definition: Chemotherapy given at shorter intervals (e.g., every 2 weeks instead of 3)
• Requirement: G-CSF support is mandatory
• Examples: Dose-dense AC-T for breast cancer (every 14 days)
• Benefit: Improved efficacy without increased toxicity when G-CSF used

ASCO Guidelines Key Points

• Primary prophylaxis recommended when FN risk >20%
• Consider for intermediate risk (10-20%) with patient risk factors
• Not routinely recommended for low risk (<10%) regimens
• Use in curative settings to maintain dose intensity
• G-CSF enables use of optimal chemotherapy doses

Dosing and Administration

Standard Dosing for Chemotherapy-Induced Neutropenia

Example Dosing Calculations

• 70 kg patient: 5 mcg/kg × 70 kg = 350 mcg daily
  • Exact: 350 mcg
  • Rounded: 300 mcg (one 300 mcg vial) - acceptable
• 90 kg patient: 5 mcg/kg × 90 kg = 450 mcg daily
  • Exact: 450 mcg
  • Rounded: 480 mcg (one 480 mcg vial) - acceptable

Alternative Dosing Strategies

• Fixed dosing: Some centers use fixed doses (300 mcg or 480 mcg) regardless of weight
• Higher doses (10 mcg/kg): Used for stem cell mobilization
• AML protocol: 5 mcg/kg/day starting >24 hours after chemotherapy, continue to ANC >1,000/mm³ for 3 consecutive days

Special Population Dosing

Pediatric Patients

• Same weight-based dosing: 5 mcg/kg/day
• Safety and efficacy established in children

Obese Patients

• Use actual body weight for dosing calculation
• No dose adjustment needed

Renal Impairment

• No dose adjustment required
• Can use in dialysis patients

Hepatic Impairment

• No dose adjustment required

Dose Modifications

• ANC >10,000/mm³: Consider discontinuing to avoid excessive elevation
• WBC >100,000/mm³: Discontinue immediately; monitor for complications
• No dose reduction for side effects: Usually discontinue if intolerable

Critical Timing Considerations

Why Timing Matters

• Chemotherapy kills rapidly dividing cells: This includes both cancer cells and bone marrow cells
• G-CSF stimulates cell division: Makes bone marrow cells divide faster
• Problem with concurrent use: G-CSF makes bone marrow cells more vulnerable to chemotherapy damage
• Result: Paradoxically worse and prolonged neutropenia

Correct Timing Protocol

Multi-Day Chemotherapy Regimens

For regimens where chemotherapy is given over multiple consecutive days:

• Rule: Start filgrastim at least 24 hours after the LAST dose of chemotherapy
• Example: If chemotherapy given days 1-5, start filgrastim on day 6 or later

Common Mistakes to Avoid

Duration of Therapy

How Long to Continue Filgrastim

Continue daily injections until ANC recovers adequately. This is typically 10-14 days but varies by patient and chemotherapy regimen.

Stopping Criteria

Discontinue filgrastim when:

• ANC >10,000/mm³ after expected nadir: Most common criterion
• ANC >1,000/mm³ for 3 consecutive days: Alternative criterion (used in some protocols)
• 24 hours before next chemotherapy: Must stop regardless of count
• Post-marrow recovery: Once bone marrow has clearly recovered

Typical Duration by Indication

What if Next Chemotherapy is Due But Still on Filgrastim?

• Priority: Stop filgrastim at least 24 hours before chemotherapy
• If ANC still low: May need to delay chemotherapy cycle
• Discuss with oncologist: Balance between timing and ANC recovery

Frequency of Administration Throughout Treatment

• Each chemotherapy cycle: Repeat filgrastim with every cycle if indicated
• Primary prophylaxis: Continue through all planned chemotherapy cycles
• Not continuous: Stop between cycles when not needed

Monitoring Parameters

Complete Blood Count (CBC) Monitoring

Key Lab Values to Monitor

• ANC (Absolute Neutrophil Count): Primary parameter
  • Goal: Maintain >1,000/mm³, ideally >1,500/mm³
  • Calculation: (% neutrophils + % bands) × total WBC
• WBC (White Blood Cell Count):
  • Normal: 4,000-11,000/mm³
  • On filgrastim: Often elevated (15,000-50,000/mm³) - expected
  • Concern if >100,000/mm³
• Platelet count: Filgrastim doesn't affect but monitor for chemotherapy effect
• Hemoglobin: Not affected by filgrastim

Clinical Monitoring

• Temperature: Daily at home; report fever immediately
• Signs of infection: Cough, dysuria, wound drainage, etc.
• Bone pain: Common side effect, assess severity
• Injection site: Check for reactions
• Spleen size: Rarely, monitor for splenomegaly (usually only in chronic use)

Baseline Assessments

Before starting filgrastim:

• CBC with differential
• Ensure no pre-existing leukemia or myelodysplastic syndrome (relative contraindication)
• Pregnancy test if applicable

Long-Term Monitoring (Chronic Neutropenia)

For patients on long-term therapy:

• CBC at least monthly, more often if adjusting dose
• Annual bone marrow exam (recommended by some experts)
• Monitor for evolution to MDS/AML (rare but reported)

Side Effects

Filgrastim is generally well-tolerated. The most common side effect is bone pain, which occurs because the bone marrow is being stimulated to produce more cells.

Serious but Rare Side Effects

Splenic Rupture (Very Rare)

Acute Respiratory Distress Syndrome (ARDS) (Very Rare)

• Incidence: Very rare
• Presentation: Fever, lung infiltrates, respiratory distress
• Management: Discontinue filgrastim, supportive care

Allergic Reactions (Rare)

• Types: Rash, urticaria, angioedema (rare), anaphylaxis (very rare)
• Risk: Higher in patients with latex allergy (needle cap contains latex)
• Management: Mild reactions may be managed with antihistamines; severe reactions require discontinuation

Cutaneous Vasculitis (Rare)

• Presentation: Palpable purpura, often on extremities
• Management: Usually resolves with discontinuation

Capillary Leak Syndrome (Very Rare)

• Symptoms: Hypotension, edema, hypoalbuminemia
• Management: Supportive care, discontinue filgrastim

Glomerulonephritis (Very Rare)

• Reports of hematuria and proteinuria
• Usually resolves with discontinuation

Theoretical Long-Term Risks

• Progression to MDS/AML:
  • Concern in patients with severe chronic neutropenia on long-term therapy
  • Risk appears low (<3% per year in chronic neutropenia)
  • May be related to underlying disease rather than filgrastim
  • Not a significant concern with short-term chemotherapy support
• Potential to stimulate tumor growth:
  • Theoretical concern (some tumors express G-CSF receptors)
  • Clinical trials have not shown increased tumor growth or decreased survival
  • Benefits generally outweigh theoretical risks

Side Effects Filgrastim Does NOT Cause

• Hair loss: Filgrastim doesn't cause alopecia
• Nausea/vomiting (severe): Not emetogenic
• Anemia: Doesn't affect red blood cells
• Thrombocytopenia: Doesn't reduce platelets
• Peripheral neuropathy: No nerve damage
• Kidney or liver damage: Not nephrotoxic or hepatotoxic

Contraindications & Precautions

Absolute Contraindications

• Serious hypersensitivity: To filgrastim, E. coli-derived proteins, or any component
• Concurrent use with chemotherapy: Within 24 hours after or 14 days before

Use with Extreme Caution

Sickle Cell Disease

• Risk: May precipitate sickle cell crisis
• Management: Use only if benefit outweighs risk; hydrate adequately; monitor closely
• Deaths reported in patients with sickle cell disease receiving filgrastim

Myeloid Malignancies

• Concern: Potential to stimulate malignant cell growth
• AML: FDA-approved but use carefully per protocol
• MDS: Generally avoided; risk of progression to AML
• Chronic myeloid leukemia (CML): Usually avoided

Special Precautions

Latex Allergy

• Warning: Needle cap contains natural rubber latex
• Risk: May cause allergic reactions in latex-sensitive individuals
• Alternative: Consider latex-free biosimilars or remove cap carefully

Pre-Existing Cardiac or Pulmonary Conditions

• Monitor closely for fluid retention, dyspnea
• Rare cases of ARDS reported

Large Tumor Burden

• Caution in lung or mediastinal tumors
• Monitor for respiratory compromise

Pregnancy and Breastfeeding

• Pregnancy Category C: No adequate human studies
• Animal studies: Adverse effects at high doses
• Use in pregnancy: Only if clearly needed and benefits outweigh risks
• Breastfeeding: Unknown if excreted in breast milk
  • Unlikely to be absorbed orally by infant (protein molecule)
  • Consider risk/benefit

Special Populations

Elderly Patients

• No dose adjustment needed
• Same efficacy and safety profile
• Important population: Age ≥65 is risk factor for febrile neutropenia

Pediatric Patients

• Safe and effective in children
• Same weight-based dosing

Renal or Hepatic Impairment

• No dose adjustment required
• Can be used safely

Drug Interactions

Major Interactions

Chemotherapy - MOST IMPORTANT

Radiation Therapy

• Interaction: Potential for increased sensitivity of rapidly dividing cells
• Recommendation: Avoid concurrent use with radiation therapy
• Sequential use: May use after radiation completed, similar to chemotherapy timing

Moderate Interactions

Lithium

• Interaction: Both increase neutrophil counts
• Effect: Additive elevation of WBC
• Management: Monitor WBC more frequently; generally not problematic

Other Drugs Affecting Myelopoiesis

• Corticosteroids: May potentiate effect on neutrophil release
• Management: Monitor blood counts

Laboratory Test Interactions

• WBC: Will be elevated (expected effect)
• ANC: Will be elevated (desired effect)
• Alkaline phosphatase: May be transiently elevated
• LDH: May be elevated
• Uric acid: May increase (from increased cell turnover)

No Significant Interactions

Pegfilgrastim (Neulasta) - Long-Acting Version

Key Differences: Filgrastim vs. Pegfilgrastim

Pegfilgrastim Mechanism

• Pegylation: Polyethylene glycol (PEG) molecule attached to filgrastim
• Effect: Slows kidney clearance, extends half-life
• Self-regulating clearance: As neutrophils increase, they clear pegfilgrastim (smart design!)
• Result: One injection provides coverage throughout the neutropenic period

Pegfilgrastim Dosing

• Dose: 6 mg (fixed dose, not weight-based)
• Route: Subcutaneous injection
• Timing: Approximately 24 hours (1 day) after chemotherapy completion
• Frequency: Once per chemotherapy cycle (every 14-21 days depending on regimen)
• Maximum: One dose per cycle - do NOT give more than once per cycle

On-Body Injector (Onpro)

• Device: Wearable automatic injector for pegfilgrastim
• How it works: Applied to skin on same day as chemotherapy; automatically delivers pegfilgrastim ~27 hours later
• Advantage: No need to return to clinic or self-inject
• Wears for: 27+ hours, then removed
• Availability: May not be at all centers

When to Choose Filgrastim vs. Pegfilgrastim

Pegfilgrastim May Be Preferred:

• Patient convenience is priority
• Difficulty with daily injections or clinic visits
• Standard 21-day chemotherapy cycles
• Insurance coverage is comparable
• Consistent with clinical guidelines

Filgrastim May Be Preferred:

• Dose-dense (14-day) chemotherapy cycles (pegfilgrastim not cleared before next cycle)
• Need to adjust duration based on counts
• Cost is a major concern (if biosimilar filgrastim significantly cheaper)
• Shorter neutropenic period expected
• Patient already comfortable with daily injections

Pegfilgrastim Biosimilars

FDA-approved biosimilars of Neulasta:

• Fulphila (pegfilgrastim-jmdb) - Mylan, 2018
• Udenyca (pegfilgrastim-cbqv) - Coherus, 2018
• Ziextenzo (pegfilgrastim-bmez) - Sandoz, 2019
• Nyvepria (pegfilgrastim-apgf) - Pfizer, 2020
• Stimufend (pegfilgrastim-fpgk) - Fresenius Kabi, 2022

All are equivalent to Neulasta with similar efficacy and safety at potentially lower cost.

Biosimilars

Biosimilars are highly similar versions of biologic drugs like filgrastim. Multiple biosimilars are available, offering equivalent efficacy at reduced cost.

FDA-Approved Filgrastim Biosimilars

What Are Biosimilars?

• Highly similar: No clinically meaningful differences in safety, purity, and potency
• NOT generic: Biologics are large, complex proteins that can't be exactly copied
• Same mechanism: Work identically to reference product
• Same indications: Approved for all uses of reference product
• Manufacturing: Different production process but same end result

Efficacy and Safety

• Clinical trials: Demonstrate equivalent efficacy to Neupogen
• ANC recovery: Same time course and magnitude
• Febrile neutropenia reduction: Equivalent protection
• Side effects: Similar incidence and types
• Immunogenicity: No increased antibody formation
• Interchangeability: Can switch between products safely

Cost Considerations

• Neupogen cost: $300-500 per 300 mcg vial
• Biosimilar cost: Typically 15-35% less expensive
• Per cycle savings: $500-2,000+ if using biosimilar
• Insurance coverage: Most plans cover biosimilars; may incentivize use

Should You Use a Biosimilar?

Advantages

• Lower cost for patients and healthcare system
• Equivalent efficacy and safety
• FDA-approved based on rigorous standards
• Increases access to treatment
• Supported by major oncology organizations (ASCO, NCCN)

Considerations

• Patient/provider comfort level
• Insurance formulary requirements
• Availability at pharmacy or treatment center
• Very rare patient preference for original product

Clinical Efficacy

Key Efficacy Data

• Reduces febrile neutropenia by ~50%
  • From 20-40% baseline risk to 10-20% with G-CSF
  • Even greater reduction in high-risk regimens
• Shortens neutropenia duration:
  • Reduces median duration by 3-7 days
  • Faster ANC recovery (typically 2-4 days earlier)
• Reduces hospitalization:
  • Fewer admissions for febrile neutropenia
  • Shorter hospital stays when admission needed
  • Reduces healthcare costs overall despite drug cost
• Reduces infection-related complications:
  • Fewer documented infections
  • Less antibiotic use
  • Lower infection-related mortality
• Maintains chemotherapy dose intensity:
  • Fewer chemotherapy dose reductions
  • Fewer treatment delays
  • More patients complete planned therapy

Impact on Survival

• Direct survival benefit: Not consistently shown in meta-analyses
• Indirect benefit: By maintaining dose intensity in curative settings
  • Dose reductions may compromise outcomes
  • G-CSF allows delivery of optimal doses on time
• Quality of life: Reduces risk of serious complications

Cost-Effectiveness

• Drug cost: $3,000-7,000 per cycle
• Hospitalization avoided: $10,000-30,000+ per febrile neutropenia episode
• Cost-effective when:
  • Febrile neutropenia risk >20% (clearly cost-effective)
  • Risk 10-20% with patient risk factors (often cost-effective)
  • Curative intent treatment where maintaining dose is critical
• Biosimilars improve cost-effectiveness

Landmark Studies

• Crawford et al. (1991): First major trial showing reduced infection and hospitalization
• Holmes et al. (2002): Meta-analysis confirming infection reduction
• CITADEL trial: Demonstrated benefit in dose-dense breast cancer regimens
• Multiple RCTs: Consistent benefit across cancer types and regimens

Administration Guidelines

Preparing for Injection

1. Gather supplies: Filgrastim vial/syringe, alcohol wipes, sharps container, cotton ball or gauze
2. Check medication:
   • Verify correct medication and dose
   • Check expiration date
   • Inspect for discoloration or particles (should be clear and colorless)
   • Do NOT shake (can denature protein)
3. Temperature: May bring to room temperature (15-30 minutes) for comfort, but not required
4. Wash hands thoroughly

Injection Sites

• Preferred sites:
  • Abdomen (most common) - at least 2 inches from belly button
  • Outer thighs
  • Upper outer arms (if someone else giving injection)
• Avoid: Areas with scars, bruises, redness, or hard lumps
• Rotate sites: Use different location each day

Injection Procedure

1. Clean injection site with alcohol wipe; let dry
2. Pinch skin to create a fold
3. Insert needle at 45-90 degree angle
4. Inject medication slowly
5. Remove needle at same angle inserted
6. Apply gentle pressure with cotton ball (don't rub)
7. Dispose of needle immediately in sharps container

Pre-Filled Syringes

• Available sizes: 300 mcg/0.5 mL, 480 mcg/0.8 mL
• Advantages: Easier to use, no drawing up medication
• Latex warning: Needle cap contains natural rubber latex
• Single-use: Discard any unused portion

Storage

• Refrigerate: 2-8°C (36-46°F) - preferred
• May leave at room temperature: Up to 72 hours (discard after)
• Do NOT freeze - discard if frozen
• Protect from light: Keep in original carton until use
• Do NOT shake

Intravenous Administration (Less Common)

• Dilution: May dilute in D5W (do NOT use normal saline)
• Concentration: Minimum final concentration 5 mcg/mL
• Albumin: Add human albumin (2 mg/mL) if diluting to <15 mcg/mL
• Infusion time: 15-30 minutes
• Compatibility: Do NOT mix with other medications

Handling Precautions

• Healthcare workers: Standard precautions; not hazardous
• Not cytotoxic: No special handling required (unlike chemotherapy)
• Sharps disposal: Required for needles/syringes

Patient Counseling Points

Before Starting Filgrastim

• Purpose: "This medication helps your body make more white blood cells to protect you from infection during chemotherapy. It's not chemotherapy itself - it's a helper medication."
• Timing: "You'll start 1-3 days after chemotherapy and continue daily until your white blood cell count recovers, usually 10-14 days."
• Injection training: "We'll teach you or a family member how to give the injections at home, or you can come to the clinic."
• Bone pain expected: "Most patients have bone pain, especially in the lower back and hips. This is normal - it means the medication is working. We'll give you pain relievers."

Self-Administration Instructions

• Proper injection technique
• Site rotation
• Storage requirements (refrigerate)
• Sharps disposal
• What to do if you miss a dose (call clinic)

Managing Bone Pain

• Expect it: "50-60% of patients have bone pain. It usually starts 2-3 days after beginning injections."
• Treatment:
  • "Take acetaminophen (Tylenol) 1000 mg every 6 hours, or ibuprofen 400-600 mg every 6-8 hours"
  • "Some patients find antihistamines (like Claritin) helpful"
  • "Warm compresses and gentle movement may help"
• Reassurance: "Pain resolves within a few days of stopping the medication"

Warning Signs to Report Immediately

What Filgrastim Does and Doesn't Do

• Does: Helps prevent serious infections by boosting white blood cells
• Does: Allows you to stay on schedule with chemotherapy
• Doesn't: Treat cancer directly - only supports you through chemotherapy
• Doesn't: Prevent all infections - still practice good hygiene and avoid sick contacts
• Doesn't: Help with other chemotherapy side effects like nausea or hair loss

When to Stop

• "Your doctor will tell you when to stop based on blood tests"
• "Usually 10-14 days, but may vary"
• "Always stop at least 24 hours before your next chemotherapy"
• "Don't stop on your own without checking with your medical team"

Cost and Insurance

• "This medication can be expensive ($300-500 per injection)"
• "Insurance usually covers it when prescribed appropriately"
• "Biosimilar versions (Zarxio, Nivestym) work just as well and may cost less"
• "Ask about patient assistance programs if cost is a concern"

Cost and Access

Cost Breakdown

Costs vary by pharmacy, insurance, dose, and geographic location. These are approximate wholesale acquisition costs.

Insurance Coverage

• Medicare Part B: Covers when given for chemotherapy support (typically 80% after deductible)
• Medicare Part D: May cover for home use
• Private insurance: Usually covered with prior authorization
  • May require documentation of high-risk regimen
  • May have preferred products (biosimilars)
• Prior authorization: Often required; oncologist provides justification

Cost-Saving Strategies

• Use biosimilars: 15-35% cheaper than brand products
• Vial optimization: Round dose to available vial sizes to minimize waste
• Compare filgrastim vs. pegfilgrastim: May depend on cycle length and insurance coverage
• Specialty pharmacy: Often better pricing than retail pharmacy

Patient Assistance Programs

• Amgen FIRST Step (Neupogen): 1-888-657-8371 or www.amgenfirststep.com
• Sandoz Patient Assistance: For Zarxio
• Pfizer Patient Assistance: For Nivestym
• Copay assistance: Available for commercially insured patients
• Foundations:
  • HealthWell Foundation
  • Patient Access Network Foundation
  • Patient Advocate Foundation

Cost vs. Benefit Perspective

• Filgrastim cost: $3,000-7,000 per cycle
• Hospitalization for febrile neutropenia: $10,000-30,000+
• Reduced complications: Antibiotics, supportive care, lost work/quality of life
• Chemotherapy effectiveness: Maintaining dose intensity may improve cure rates
• Bottom line: Generally cost-effective for appropriate indications

Access Issues

• Availability: Widely available in US
• Shortages: Occasionally occur but alternatives usually available
• Rural areas: May require specialty pharmacy mail order
• International: Available in most countries; pricing varies widely

Related Information

References

1. Neupogen (filgrastim) [package insert]. Thousand Oaks, CA: Amgen Inc.; 2024.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 1.2026.
3. Smith TJ, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212.
4. Crawford J, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991;325(3):164-170.
5. Holmes FA, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002;13(6):903-909.
6. Aapro MS, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8-32.
7. Kuderer NM, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10):2258-2266.
8. Lyman GH, et al. Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Canc Netw. 2009;7(1):99-108.