ModifiedPremera BluecrossPolicy N/A

Use of Granulocyte Colony-Stimulating Factors (G-CSF)

Defines medical and pharmacy coverage criteria, preferred products, and authorization requirements for G-CSF agents for Premera Bluecross members, including oncology-related prophylaxis and other indicated uses.

Policy Summary

PayerPremera Bluecross

PolicyUse of Granulocyte Colony-Stimulating Factors (G-CSF)

Policy CodePolicy N/A

Change TypeCoverage expansions and biosimilar additions

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization when billing listed HCPCS/CPT codes for G-CSF agents unless using Granix or Nivestym, which do not require preapproval.

SourceLink

POLICY UPDATE CHANGES

Added Filkri (filgrastim-laha) and Armlupeg (pegfilgrastim-unne) to the policy for multiple indications including myelosuppressive chemotherapy and hematopoietic subsyndrome of acute radiation syndrome.

Updated coverage to add therapy for several agents (Nypozi, Stimufend, Udenyca and Udenyca Onbody) for individuals acutely exposed to myelosuppressive doses of radiation.

Moved Udenyca (pegfilgrastim-cbqv) into earlier line(s) of therapy for pediatric and adult populations and changed Nyvepria (pegfilgrastim-apgf) placement in prior updates.

Added several products previously listed as non-preferred (Ryzneuta, Udenyca Onbody, Nypozi) and clarified non-formulary exception approvals may be up to 12 months.

2Preferred agents without preapproval

18+HCPCS/CPT/J-codes listed

12 mo

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Max non-formulary exception

>20%ASCO FN risk threshold

2026Most recent update year

Coverage Criteria for G-CSF Agents

Prophylaxis with Myelosuppressive Anti-Cancer Regimens (to decrease incidence of infection/febrile neutropenia)

Covered when criteria below are met; coverage is tiered by product line (first-line, second-line, third-line) and indication.

First-line filgrastim agents: Granix (tbo-filgrastim) or Nivestym (filgrastim-aafi) may be considered medically necessary as first-line therapy to decrease the incidence of infection for adult and pediatric individuals treated with myelosuppressive anti-cancer regimens at risk of severe febrile neutropenia.

Granix and Nivestym do not need preapproval for coverage.

Second-line filgrastim agents: Filkri, Neupogen, Nypozi, Releuko, and Zarxio may be considered medically necessary when documentation shows trial and failure of Granix or Nivestym OR there is a contraindication to both Granix and Nivestym.

Fulphila/Udenyca pegfilgrastim biosimilars (specific rules): Fulphila and Udenyca (including Udenyca Onbody) may be considered medically necessary for adults when documentation shows trial and failure of Granix or Nivestym OR contraindication to both, or when pegfilgrastim was the only G-CSF used in published trials (provider should supply citations).age >= 18 for some provisions

Also may be first-line for individuals <18 in some listings; see policy for age-specific rules.

Third-line pegfilgrastim agents: Armlupeg, Fylnetra, Neulasta (including Neulasta Onpro), Nyvepria, Stimufend, Ziextenzo and other listed pegfilgrastim agents may be considered medically necessary for adults when: age >= 18; documentation shows trial and failure of Granix or Nivestym OR contraindication to both; AND trial and failure of Fulphila AND Udenyca (or contraindication to both Fulphila and Udenyca) as applicable.age >=18

For pediatric <18 there are separate sequences requiring trials of pegfilgrastim biosimilars first.

Other Indications (stem cell mobilization, congenital/idiopathic neutropenia, radiation exposure)

Other medically necessary uses (non-oncology indications) per product-specific rules:

Autologous PBPC collection: Nivestym (filgrastim-aafi) may be considered medically necessary as first-line for autologous peripheral blood progenitor cell collection and therapy.

Applies to adult and pediatric individuals as labeled.

Symptomatic congenital/cyclic/idiopathic neutropenia: Nivestym may be considered medically necessary as first-line to reduce incidence and duration of severe neutropenia sequelae in symptomatic congenital, cyclic, or idiopathic neutropenia; other filgrastim products (Filkri, Neupogen, Nypozi, Releuko, Zarxio) may be second-line when trial and failure of Nivestym or contraindication to Nivestym is documented.

Documentation of trial/failure or contraindication required for second-line use.

Acute radiation exposure (Hematopoietic Subsyndrome of ARS): Filgrastim products (Filkri, Neupogen, Nypozi, Releuko, Zarxio) may be considered medically necessary as first-line therapy for adults and pediatric individuals acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).

High-risk FN criteria

Considered at risk of severe FN when ANY of the following are present:

High-risk febrile neutropenia features: Prior febrile neutropenia on the current chemotherapy regimen; OR receipt of a chemotherapy regimen with expected FN incidence >= 20% (per ASCO guidelines); OR bone marrow impairment; OR receipt of 2 or more prior chemotherapy regimens or extensive radiation; OR presence of other serious comorbidities (case-by-case review).>=20% where specified

Colony-stimulating factors should not be routinely used for afebrile neutropenia.

Coverage aligned with labeled indications and ASCO guideline threshold

Covered when consistent with FDA-labeled indications for each product and guideline-based use (e.g., ASCO recommendation):

Alignment with product labeling: Use consistent with product-specific labeled indications such as support during myelosuppressive chemotherapy, adjunct to AML chemotherapy, bone marrow transplant support, progenitor cell collection, severe chronic neutropenia, and acute radiation syndrome as labeled per product table.see product labels

See Table 1 summary of labeled indications in the policy.

ASCO guideline threshold: For prophylactic use, ASCO recommends G-CSF when the risk of febrile neutropenia from the chemotherapy regimen is greater than 20% unless an equally effective regimen that does not require G-CSF is available.> 20% FN risk

Exceptions may apply for individual high-risk features (age, comorbidities).

Summary of recent coverage changes

Policy updates and coverage expansions noted in annual updates

Recent material updates: Policy history documents additions of biosimilars (e.g., Ziextenzo, Releuko, Fylnetra, Ryzneuta, Filkri, Armlupeg) and expansion of coverage to include acute radiation syndrome and other indications; therapy-line preferences and coding updates (HCPCS/Q/J codes) were revised across 2020–2026 updates.

See history entries for specific effective dates and code changes.

Primary medical necessity criteria

Covered when chemotherapy regimen has a predicted risk of febrile neutropenia >20% or other specified indications

Primary indications: G-CSF therapy is covered for individuals receiving myelosuppressive anti-cancer regimens with predicted FN risk >20%; for autologous peripheral blood progenitor cell collection; and for individuals acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).FN risk >20%

Specific regimens with documented FN percentages are listed in the policy appendix (Smith et al, 2006).

Any uses of the G-CSF products that are not explicitly addressed in this policy are classified as investigational. The policy lists specific agents and states that uses beyond the product-specific coverage criteria and labeled indications are considered investigational and subject to FDA dosing and administration guidance.

The policy specifies that colony-stimulating factors should not be routinely used for afebrile neutropenia. This reflects guideline-based practice and is cited in the policy text (Smith et al., 2006) as the rationale for considering routine treatment of afebrile neutropenia not supported.

Requests for G-CSF agents are contraindicated for individuals with a history of serious allergic reactions to human G-CSFs. The policy lists multiple products (e.g., Filkri, Fulphila, Fylnetra, Granix, Neulasta, Neupogen, Nivestym, Zarxio, Ziextenzo, and others) and states these are contraindicated in members with prior serious allergic reactions to pegfilgrastim- or filgrastim-containing products; Rolvedon and Ryzneuta have analogous specific listings.

The policy identifies certain biosimilar products as non-preferred, which may limit coverage unless a non-formulary exception or prior authorization rationale is provided. The 2024 update specifically added some agents (e.g., Ryzneuta and Udenyca Onbody) as non-preferred treatments for prophylaxis in individuals receiving myelosuppressive chemotherapy at risk of febrile neutropenia.

This medical policy applies to Premera Bluecross members generally but explicitly states that it does not apply to Medicare Advantage plans. Providers should verify coverage and benefit limits with the member's specific plan.

The policy references Smith et al. (2006) to note that the routine use of colony-stimulating factors for afebrile neutropenia is not supported. Such routine use is considered not medically necessary under the policy unless specific criteria indicating high risk of febrile neutropenia are met.

Coverage under this policy is subject to member benefit limits and contract exclusions. Members and providers must consult the member benefit booklet or customer service to determine whether the service is covered under the member's plan; lack of coverage under the member's contract may result in denial.

Coding and Billing Codes

CPT CodesCPT

96377

Application of on-body injector (includes cannula insertion) for timed subcutaneous

HCPCS / J / Q CodesHCPCS

C9173	Injection, filgrastim-txid (Nypozi), biosimilar, 1 microgram (code terminated 07/01/25).
J1442	Injection, filgrastim (G-CSF) (Neupogen), 1 microgram.
J1449	Injection, eflapegrastim-xnst (Rolvedon), 0.1 mg.
J2506	Injection, pegfilgrastim (Neulasta), excludes biosimilar, 0.5 mg.
J3590	Unclassified biologics (use to report: Filkri, Armlupeg).
J9361	Injection, efbemalenograstim alfa-vuxw (Ryzneuta), 0.5 mg.
Q5101	Injection, filgrastim-sndz, biosimilar (Zarxio), 1 microgram.
Q5108	Injection, pegfilgrastim-jmdb (Fulphila), biosimilar, 0.5 mg.
Q5111	Injection, pegfilgrastim-cbqv (Udenyca), biosimilar, 0.5 mg.
Q5120	Injection, pegfilgrastim-bmez (Ziextenzo), biosimilar, 0.5 mg.

1–10 of 15

1/2

Covered CPT CodesCPTCovered

96377

Application of on-body injector (includes cannula insertion) for timed subcutaneous

Covered HCPCS/J and Q codesHCPCSCovered

C9173	Injection, filgrastim-txid (Nypozi), biosimilar, 1 microgram.
J1442	Injection, filgrastim (G-CSF) (Neupogen), 1 microgram.
J1449	Injection, eflapegrastim-xnst (Rolvedon), 0.1 mg.
J2506	Injection, pegfilgrastim (Neulasta), excludes biosimilar, 0.5 mg.
J3590	Unclassified biologics (use to report: Filkri, Armlupeg).
J9361	Injection, efbemalenograstim alfa-vuxw (Ryzneuta), 0.5 mg.
Q5101	Injection, filgrastim-sndz, biosimilar (Zarxio), 1 microgram.
Q5108	Injection, pegfilgrastim-jmdb (Fulphila), biosimilar, 0.5 mg.
Q5111	Injection, pegfilgrastim-cbqv (Udenyca), biosimilar, 0.5 mg.
Q5120	Injection, pegfilgrastim-bmez (Ziextenzo), biosimilar, 0.5 mg.

1–10 of 15

1/2

HCPCS / Q and unclassified biologics codes referenced in historyHCPCS

J3590	Unclassified biologics (used to report various pegfilgrastim/filgrastim biosimilars as listed in policy)
J2506	Pegfilgrastim (Neulasta) description updated in policy history
J9361	HCPCS code added effective 7/1/2024 (policy history reference)
Q5108	HCPCS/Q-code referenced in policy history
Q5110	HCPCS/Q-code referenced in policy history
Q5120	HCPCS/Q-code referenced in policy history
Q5122	HCPCS/Q-code referenced in policy history
Q5125	HCPCS/Q-code referenced in policy history
Q5127	HCPCS/Q-code referenced in policy history
Q5130	HCPCS/Q-code referenced in policy history

1–10 of 11

1/2

Febrile neutropenia risk threshold

Expected incidence threshold>= 20% expected incidence of febrile neutropenia

Use caseUsed to identify chemotherapy recipients who may need prophylactic G-CSF

Guideline source referencedASCO guideline threshold referenced in policy (Smith et al, 2006)

ASCO febrile neutropenia risk threshold

ASCO recommendation threshold> 20% risk of febrile neutropenia to use G-CSF prophylaxis

Context

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required when billing any listed G‑CSF HCPCS/CPT codes or when requesting coverage for an on‑body injector application (CPT 96377). Granix (tbo‑filgrastim) and Nivestym (filgrastim‑aafi) are preferred and do not require preapproval; use of other G‑CSF agents generally requires prior authorization.

Prior authorization required for listed HCPCS/CPT codes and CPT 96377 (on‑body injector).
Granix and Nivestym are preferred and do not require preapproval; all other G‑CSF agents require prior authorization.

Prior Authorization

Indication and Benefit Verification

Prior authorization requests must verify the indication and that benefit coverage applies. Approvals are granted only when the indication aligns with labeled uses and guideline thresholds (for example, chemotherapy regimens with ≥20% FN risk or individuals meeting the policy’s high‑risk criteria). The request should state whether the drug will be billed under the medical benefit (provider administration) or the pharmacy benefit (self‑administered/non‑professional caregiver).

Confirm indication aligns with labeled indications and ASCO guideline thresholds (e.g., >=20% FN risk) or documented individual high‑risk factors.

Background and Rationale

G-CSF agents stimulate production of neutrophils and are used to reduce the incidence and duration of neutropenia and febrile neutropenia in patients receiving myelosuppressive chemotherapy. The policy describes filgrastim and pegfilgrastim class agents (recombinant human G-CSF and pegylated long‑acting formulations) and notes their clinical role in accelerating neutrophil recovery, reducing febrile neutropenia, hospitalizations, and use of IV antibiotics.

Definitions and Key Terms

Neutropenia / febrile neutropenia definition

DefinitionNeutropenia: deficiency of granulocytes (neutrophils) that increases risk of infection; febrile neutropenia: neutropenia accompanied by fever requiring evaluation and often inpatient antibiotics

Clinical significanceCan lead to serious infection during chemotherapy; G-CSF agents reduce incidence and duration of neutropenia and FN

Policy implicationG-CSF prophylaxis considered for individuals at high risk of FN (e.g., prior FN, regimen with >=20% FN risk, bone marrow impairment)

Pegfilgrastim — definition and description

Drug class descriptionPegfilgrastim is a covalent conjugate of recombinant methionyl human G-CSF (filgrastim) and monomethoxypolyethylene glycol (long-acting G-CSF)

Typical indication

Initial Therapy Criteria and Preferences

Initial Therapy

Initial therapy preferences and first-line agents

First-line: Granix (tbo-filgrastim) and Nivestym (filgrastim-aafi) are the preferred first-line filgrastim agents for decreasing incidence of infection in individuals treated with myelosuppressive anti-cancer regimens at risk of severe febrile neutropenia; these agents do not require preapproval.

Applies to adult and pediatric use as specified in policy.

Initial therapy and product labeling

Initial therapy indications and product notes:

Product-specific labeling: Products carry labeled indications to reduce duration of severe neutropenia and incidence of febrile neutropenia in non-myeloid malignancies receiving myelosuppressive chemotherapy; pegfilgrastim formulations (Neulasta and biosimilars) are single-dose pegylated agents while filgrastim agents are daily formulations—use should follow labeled dosing and administration.per label

Re-authorization and Continuation Criteria

Re-authorization

Re-authorization length: All drugs listed may be approved for re-authorization for up to 12 months provided the drug-specific coverage criteria are met and chart notes document continued positive clinical response.12 months

Step Therapy Sequencing and Requirements

Step	Required prior trial(s) or condition	Products in this step	Coverage label
1	First-line: No prior trial required; preferred filgrastim agents do not require preapproval	Granix (tbo-filgrastim); Nivestym (filgrastim-aafi)	Covered
2	Requires documentation of trial and failure of Granix or Nivestym OR documented contraindication to both preferred agents	Filkri (filgrastim-laha); Neupogen (filgrastim); Nypozi (filgrastim-txid); Releuko (filgrastim-ayow); Zarxio (filgrastim-sndz)	Covered
2 (alternate for long-acting in some adults / first-line in <18)	Adults: trial and failure of Granix or Nivestym OR contraindication to both. Pediatrics (<18): may be considered first-line in specified listings	Fulphila (pegfilgrastim-jmdb); Udenyca (pegfilgrastim-cbqv); Udenyca Onbody	Covered
3	Adults: age ≥18 AND trial and failure of Granix or Nivestym (or contraindication) AND trial and failure of Fulphila and Udenyca (or contraindication to both)	Armlupeg (pegfilgrastim-unne); Fylnetra (pegfilgrastim-pbbk); Neulasta (pegfilgrastim) / Neulasta Onpro; Nyvepria (pegfilgrastim-apgf); Stimufend (pegfilgrastim-fpgk); Ziextenzo (pegfilgrastim-bmez)	Covered

Product	Change in therapy-line placement	Affected population / note	Citation
Udenyca (pegfilgrastim-cbqv) / Udenyca Onbody	Moved from second-line to first-line for individuals <18; moved from third-line to second-line for adults in prior updates	Pediatric (<18): first-line in specified listings; Adults: second-line (recent history updates)	chunks 61, 86
Nyvepria (pegfilgrastim-apgf)	Moved from first-line to second-line for individuals <18; moved from second-line to third-line for adults	Placement differs by age: pediatric vs adult	chunks 61, 86
Fulphila (pegfilgrastim-jmdb)	Moved from third-line to second-line for adults in earlier history updates	Adults: second-line (history reflects prior reclassification)	chunk 86

Sequence position	Enforced sequencing rule	Examples (branded / biosimilar groups)	Operational effect
First-line	Preferred filgrastim agents (Granix, Nivestym) are designated first-line; in some pediatric listings certain pegfilgrastim biosimilars may be first-line	Granix; Nivestym; (certain listings: Fulphila, Udenyca for <18)	Preapproval not required for Granix and Nivestym; other agents require step documentation
Second-line	Non-preferred filgrastim biosimilars and some pegfilgrastim biosimilars are second-line when trial/failure of first-line documented or contraindication present	Filkri; Neupogen; Zarxio; Releuko; Fulphila or Udenyca (depending on age and prior updates)	Coverage requires documentation of prior trial/failure or contraindication to first-line agents
Third-line	Remaining branded pegfilgrastim and biosimilar products are third-line for adults and require prior trials of first- and second-line pegfilgrastim agents	Armlupeg; Fylnetra; Neulasta / Neulasta Onpro; Nyvepria; Stimufend; Ziextenzo	Coverage requires documented trials and failures per policy sequence (age-dependent rules apply)

Site of Care and Administration

Billing Rule

Report on‑body injector application with CPT 96377

Report on‑body injector application with CPT 96377 (application of on‑body injector includes cannula insertion and the timed subcutaneous injection) and bill drug/device per the policy coding guidance.

Billing Rule

On‑body injector products recognized; include CPT 96377 for application

On‑body injector formulations (e.g., Neulasta Onpro, Udenyca Onbody) are recognized in the policy; when applicable include the on‑body device notation and use CPT 96377 for the application.

Billing Rule

Indicate medical vs pharmacy benefit for billing/authorization

State whether the product will be managed under the medical benefit (administered by a provider) or pharmacy benefit (self‑administered) when requesting authorization or billing; the policy allows either pathway depending on administration.

Biosimilar Products and Preferences

Billing Rule

Granix is preferred filgrastim and does not require preapproval

Granix (tbo‑filgrastim) is identified as a preferred filgrastim agent that does not require preapproval.

Billing Rule

Granix and Nivestym are first‑line for multiple indications including stem cell mobilization

Granix and Nivestym are first‑line filgrastim agents for several indications, including use to decrease incidence of infection with myelosuppressive chemotherapy and for stem cell mobilization in some listings.

Billing Rule

Neupogen and multiple filgrastim biosimilars listed; follow policy sequencing

Neupogen (filgrastim) and multiple filgrastim biosimilars (Zarxio, Releuko, Nypozi, Filkri, etc.) are enumerated in the policy; these products are covered per the policy but often require trial of preferred agents or meet second‑line rules.

Policy Summary

PayerPremera Bluecross

PolicyUse of Granulocyte Colony-Stimulating Factors (G-CSF)

Policy CodePolicy N/A

Change TypeCoverage expansions and biosimilar additions

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization when billing listed HCPCS/CPT codes for G-CSF agents unless using Granix or Nivestym, which do not require preapproval.

SourceLink

On This Page

Product-specific labeling and recent policy updates expanded coverage to include this indication.

ASCO advises G-CSF when FN risk from the regimen is >20% and equally effective regimens without G-CSF are unavailable

ExceptionsMake exceptions for individuals at high risk due to age, comorbidities, or disease characteristics

Predicted Febrile Neutropenia Risk — regimens listed with >20% FN risk

DefinitionRegimens listed in policy with predicted FN risk greater than 20% (examples below)

Example regimens (selected)Carboplatin + Paclitaxel (FN 21%), Dose-dense AC followed by Paclitaxel (>20%), Docetaxel (FN 21%), MVAC (FN 26%)

Source of regimen listPolicy Appendix list of chemotherapy regimens with documented FN percentages >20%

Predicted febrile neutropenia risk — >20% for listed regimens

Criterion threshold> 20% predicted risk of febrile neutropenia for listed regimens

Examples from listDose-dense Cyclophosphamide + Epirubicin + Fluorouracil (FN 71%), Vinblastine + Ifosfamide + Cisplatin (FN 67-71%), BEACOPP (FN 54%)

Intended useUsed to determine eligibility for prophylactic G-CSF per policy and ASCO guidance

Specify intended benefit application: medical benefit vs pharmacy benefit.

Prior Authorization

Prior Authorization and Product Sequencing

Prior authorization for G‑CSF agents follows the policy’s product‑line sequencing: Granix and Nivestym are first‑line preferred products for prophylaxis; other filgrastim and pegfilgrastim products are second‑ or third‑line per the policy and recent updates. Non‑preferred agents (including recently added non‑preferred listings) may require failure of or contraindication to preferred agents before approval.

Granix and Nivestym preferred first‑line for prophylaxis; other agents require prior authorization and meet step/line‑of‑therapy rules.
Non‑preferred products (e.g., Nypozi added as non‑preferred) may require documentation of trial and failure of preferred agents or valid contraindication.

Billing Rule

Billing and Coding Requirements

Use the policy’s specified billing and HCPCS/CPT codes when submitting requests. CPT 96377 (on‑body injector application) is billable and inclusive of injector and drug for Neulasta Onpro; report drug codes per HCPCS/J‑codes/Q‑codes listed in the policy.

Use CPT 96377 for on‑body injector application (Neulasta Onpro).
Report biologic drug administration using the HCPCS/J/Q codes listed in the policy (e.g., J1442, J2506, J9361, Q5101, Q5111, Q5120, Q5122, Q5148).
Unlisted biologics may be reported with J3590 where applicable (policy coding guidance).

Prior Authorization

Use of Non‑preferred G‑CSF Agents

If prescribing G‑CSF agents other than Granix or Nivestym, include clear clinical justification: documentation of trial and failure of Granix or Nivestym, a documented contraindication to both, or a valid medical rationale (for example, inability to self‑inject or lack of home nursing). Lack of preapproval or missing justification may lead to denial.

Document trial and failure of Granix or Nivestym OR documented contraindication to both.
Valid medical rationale accepted: inability to self‑inject or absence of home nursing support.
Absence of required justification or preapproval for non‑preferred agents may trigger claim denial.

Denial Risk

Denial Triggers

Denials may be issued when requests lack evidence that the individual meets high‑risk criteria for febrile neutropenia (prior FN on current regimen, regimen with ≥20% FN risk, bone marrow impairment, ≥2 prior chemo regimens, or other documented serious comorbidities) or when required documentation is missing.

Requests without documentation of high FN risk (per policy criteria) are at risk for denial.
Missing office visit notes, diagnosis, medication history, or targeted use information may result in denial.

Denial Risk

Contraindications and Denial Risk

Individuals with a history of serious allergic reactions to human G‑CSFs are contraindicated for the listed agents. Prior authorization should exclude coverage for contraindicated individuals; such history is a denial reason.

Contraindication: history of serious allergic reaction to human G‑CSFs (applies to listed filgrastim/pegfilgrastim products).
Rolvedon and Ryzneuta have specific contraindication language related to their molecular forms—verify product‑specific contraindications.

Note

Formulary, Dosing Compliance, and Benefit Limitations

Coverage is subject to the drug’s FDA‑approved dosage and administration. The medications in this policy may be managed under either the medical or pharmacy benefit; benefit plan limits and member contract terms apply and may limit coverage or cause denials.

Approvals follow FDA dosing and administration instructions.
Verify member benefit plan limits and contract terms — coverage may be denied based on benefit exclusions or limits.
Indicate whether the drug will be billed under the medical or pharmacy benefit on the authorization request.

Documentation Required

Required Medical Record Documentation

Medical records submitted for prior authorization and retrospective review must document medical necessity. Include office visit notes with diagnosis, targeted G‑CSF use, relevant history, physical exam, and medication history; additionally include documentation supporting FN risk (regimen risk, prior FN, comorbidities, bone marrow impairment, or prior chemotherapy exposures).

Office visit notes must contain diagnosis, targeted G‑CSF use, relevant history, physical evaluation, and medication history.
Provide documentation supporting high FN risk per policy criteria (e.g., prior FN, regimen ≥20% FN risk, bone marrow impairment, ≥2 prior regimens).

Note

Non‑Formulary Exception Duration

Non‑formulary exception authorizations for drugs in this policy may be approved for up to 12 months. Include the expected duration of therapy and rationale in the request.

Non‑formulary exception approvals may be granted for up to 12 months.
Include treatment duration and supporting rationale when requesting an exception.

Step Therapy

Step Therapy and Product‑Line Sequencing

Step therapy and sequencing rules apply: preferred short‑acting agents (Granix, Nivestym) are first‑line for prophylaxis with myelosuppressive regimens; other filgrastim/pegfilgrastim products are positioned as second‑ or third‑line depending on age and indication per the policy updates. Requests must document prior trials, failures, or contraindications where required by the step sequence.

Granix and Nivestym are preferred first‑line for prophylaxis; Fulphila/Udenyca/Udenyca Onbody and others have age‑ and indication‑based positioning.
Document prior trial/failure or contraindication to preferred agents when seeking approval for second‑ or third‑line products.

Decreases incidence of infection (FN) in individuals receiving myelosuppressive chemotherapy associated with clinically significant FN risk

Formulations/devicesAvailable as standard subcutaneous injection and on-body injector (Neulasta Onpro) formulations

Filgrastim — definition and description

Drug class descriptionFilgrastim is recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF), a 175–amino-acid protein produced by recombinant DNA technology

IndicationsIndicated to decrease incidence of infection (febrile neutropenia) in individuals receiving myelosuppressive chemotherapy and for other labeled uses (AML, transplantation, PBPC collection, severe chronic neutropenia)

FormulationsAvailable as multiple branded and biosimilar filgrastim products (IV/SC administration)

Ziextenzo (pegfilgrastim-bmez) — product identifier

Product identifierZiextenzo (pegfilgrastim-bmez)

DescriptionA biosimilar to Neulasta — pegfilgrastim-bmez is pegylated filgrastim (covalent conjugate of recombinant methionyl human G-CSF and PEG)

Policy noteIncluded among pegfilgrastim biosimilars covered by the policy

Stimufend (pegfilgrastim-fpgk)

Product identifierStimufend (pegfilgrastim-fpgk)

DescriptionA biosimilar to Neulasta — pegfilgrastim-fpgk is pegylated filgrastim (covalent conjugate of recombinant methionyl human G-CSF and PEG)

Policy noteListed among pegfilgrastim biosimilars covered by the policy

Rolvedon (eflapegrastim-xnst) — product identifier and mechanism note

Product identifierRolvedon (eflapegrastim-xnst)

Mechanism noteEflapegrastim-xnst is produced by covalent coupling of a human G-CSF analog and an Fc fragment (via PEG linker), forming a larger fusion molecule

Policy placementIncluded in policy drug list with labeled indications as applicable

Ryzneuta (efbemalenograstim alfa-vuxw) — product identifier

Product identifierRyzneuta (efbemalenograstim alfa-vuxw)

DescriptionRecombinant fusion protein of human G-CSF and IgG2 Fc that forms covalently-linked dimers; molecular weight ~93.4 kDa

Policy noteListed among covered biosimilar/novel G-CSF products in the policy

Acute radiation syndrome — Hematopoietic Subsyndrome described in policy

Syndrome describedHematopoietic Subsyndrome of Acute Radiation Syndrome

Policy inclusionPolicy includes use of filgrastim/pegfilgrastim products for individuals acutely exposed to myelosuppressive doses of radiation

Typical indicationUse intended to treat hematopoietic complications following acute radiation exposure as labeled per product

Regimens with Predicted Risk of Febrile Neutropenia >20% — enumerated regimen list

List purposeEnumerated chemotherapy regimens with documented predicted FN risk >20% used to identify high-risk patients for G-CSF prophylaxis

Examples (selected)Carboplatin + Paclitaxel (FN 21%), Docetaxel (FN 21%), Dose-dense FEC (FN 71%), MVAC (FN 26%), Vinblastine+Ifosfamide+Cisplatin (FN 67-71%)

Usage guidanceRegimen-specific FN percentages in this list inform application of the >=20% threshold and ASCO recommendations for prophylactic G-CSF

Granix was independently reviewed by FDA and shares FN labeling with filgrastim; Neulasta is pegfilgrastim (single-dose) with Onpro device formulation.

Evidence supporting initiation

Efficacy evidence summary relevant to initiating therapy

Filgrastim evidence: Filgrastim (Neupogen) and filgrastim biosimilars have demonstrated acceleration of neutrophil recovery and reduction in febrile neutropenia, hospitalizations, and IV antibiotic use in randomized trials; Granix demonstrated reduced duration of severe neutropenia versus placebo in a phase III trial.per label

Efficacy data summarized from phase III trials.

Pegfilgrastim evidence: Pegfilgrastim (Neulasta) reduced hospitalizations and IV anti-infective use for FN versus placebo in phase III study; single-dose pegfilgrastim provides comparable neutrophil support vs daily filgrastim in trials.per label

Therapy-line placement changes

Therapy-line designations were revised for certain agents

Therapy-line updates: Policy moved several pegfilgrastim products between first-, second-, and third-line positions for pediatric and adult populations (e.g., Udenyca placements and Nyvepria movement) and clarified non-formulary exception durations; these placement changes may affect step therapy sequencing.

See 2025 history details for effective dates and specifics.

Initial therapy and product preference

Product-line sequencing by age and indication

Age-based product preferences: The policy specifies different first-line, second-line, and third-line G-CSF product preferences depending on pediatric (<18) versus adult populations and indication (e.g., FN prophylaxis vs radiation exposure); historically some pegfilgrastim biosimilars were designated first-line for individuals <18.

Refer to policy tables for exact age- and indication-based sequencing.

Note

Exceptions for inability to self‑inject considered on medical rationale (historically geographic issues noted)

The policy historically considered geographic or inability to self‑inject when evaluating exceptions; current excerpts note geographic language was removed and decisions should be based on valid medical rationale (inability to self‑inject or receive home nursing).

Billing Rule

Neulasta and multiple pegfilgrastim biosimilars enumerated; follow product criteria

Neulasta (pegfilgrastim) and multiple pegfilgrastim biosimilars/formulations (Fulphila, Udenyca, Ziextenzo, Nyvepria, Stimufend, Armlupeg, Fylnetra, etc.) are listed in the policy and covered according to the product‑specific sequencing and criteria.

Billing Rule

Ziextenzo listed among covered pegfilgrastim biosimilars

Ziextenzo and other listed pegfilgrastim biosimilars are included among pegfilgrastim biosimilars covered by the policy.

Billing Rule

Stimufend included among covered pegfilgrastim biosimilars

Stimufend and other biosimilars are explicitly listed and included among pegfilgrastim biosimilars covered by the policy.

Billing Rule

Filkri added as a biosimilar to Neupogen with coverage (2026)

Filkri (filgrastim‑laha) was added to the policy in 2026 as a biosimilar to Neupogen with coverage for chemotherapy prophylaxis, acute radiation exposure, and certain neutropenia disorders.

Billing Rule

Armlupeg added as a pegfilgrastim biosimilar with coverage (2026)

Armlupeg (pegfilgrastim‑unne) was added to the policy as a pegfilgrastim biosimilar with coverage for chemotherapy prophylaxis and acute radiation exposure.

Billing Rule

Some filgrastim products (e.g., Nypozi) listed as non‑preferred for all indications

Policy history notes filgrastim products (e.g., Nypozi) were designated non‑preferred for all labeled indications (added 2024); check product preference status before requesting authorization.

Billing Rule

Follow updated first/second/third‑line product preferences by age and indication

The policy defines first‑, second‑ and third‑line product preferences that have been adjusted over time by age group and indication; follow the policy’s sequence when requesting coverage for specific agents.