Medical Policy: Colony Stimulating Factors: Ziextenzo TM (pegfilgrastim-bmez)

Coverage Summary

Ziextenzo (pegfilgrastim-bmez) is a pegylated colony stimulating factor biosimilar that stimulates hematopoietic cells and is used to reduce the risk of febrile neutropenia in patients receiving myelosuppressive chemotherapy. This policy (policy_number MG.MM.PH.206, status CURRENT) follows available clinical literature, evidence-based guidelines and the product's regulatory status to define medical necessity. Coverage stance is covered_with_criteria; specific criteria, step therapy, dosing limits, and prior authorization requirements apply. Coverage rules and applicability are provided across Commercial, Medicaid, and Medicare members, noting that individual member benefit programs and applicable legal mandates (including CMS requirements) govern final coverage determinations.

Quick facts / key thresholds

Authorization duration6 months

Standard dose per administration6 mg subcutaneously

Billable units per 6 mg dose12 units

Primary procedure codeQ5120

G-CSF course triggeringExpected use for 5 consecutive days or more

Initial Approval Criteria

Ziextenzo may be considered medically necessary if ONE of the below conditions is met AND use is consistent with the medical necessity criteria that follows:

ANY of the following

Step therapy / product preference: The patient has failed treatment with Neulasta AND Udenyca or they are contraindicated; OR Neulasta and Udenyca are the preferred agents for Commercial, Medicaid, and Medicare members.
Step therapy requirement: patient must trial Neulasta AND Udenyca prior to Ziextenzo (Commercial, Medicaid, and Medicare members are subject to this step therapy per policy history).
Continuing therapy: The patient is continuing previously established therapy with Ziextenzo for their current chemotherapy regimen
Access / home health: A member does not have access to, or benefits for, home health services

Prophylactic Use Criteria — Febrile Neutropenia Risk

Prophylactic use in patients with solid tumors or non-myeloid malignancy

Coverage provided when criteria regarding expected incidence of febrile neutropenia and patient risk factors are met:

Prophylactic use in solid tumors or non-myeloid malignancy

>20% risk: Patient is undergoing myelosuppressive chemotherapy with an expected incidence of febrile neutropenia of greater than 20%>20%
10-20% risk plus risk factors: Patient is undergoing myelosuppressive chemotherapy with an expected incidence of febrile neutropenia of 10% to 20% AND one or more patient-related risk factors10-20%
See list of patient-related risk factors

Definitions — Febrile Neutropenia

Definition of febrile neutropenia

Temperature criterion: Temperature: a single temperature >= 38.3 C orally or >= 38.0 C over 1 hour>=38.3 C orally or >=38.0 C over 1 hour
Neutropenia criterion: Neutropenia: <500 neutrophils/mcL OR <1,000 neutrophils/mcL with a predicted decline to <500 neutrophils/mcL over the next 48 hours<500 neutrophils/mcL or <1000 with predicted decline to <500 in 48 hrs

Febrile neutropenia: defined as temperature >= 38.3 C orally or >= 38.0 C over 1 hour AND neutropenia of <500 neutrophils/mcL OR <1,000 neutrophils/mcL with a predicted decline to <500 neutrophils/mcL within 48 hours.

Ziextenzo: defined in this policy as pegfilgrastim-bmez, a colony stimulating factor biosimilar that acts on hematopoietic cells by binding to specific cell surface receptors, stimulating proliferation, differentiation, commitment, and end-cell functional activation.

Continuation, Limitations and Renewal

Continuing therapy

Continuation detail from Initial Approval Criteria:

Continuing therapy requirement: The patient is continuing previously established therapy with Ziextenzo for their current chemotherapy regimen

This reflects continuation of previously established therapy as a standalone qualifying branch under Initial Approval Criteria.

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title': 'Continuing therapy'

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Dosage and Administration Constraints

Numeric dosing thresholds

Acute radiation exposure dosing interval6 mg subcutaneously weekly for 2 doses

Standard dosing frequency6 mg once per chemotherapy, no more frequently than every 14 days

Authorization duration6 months

G-CSF course triggeringExpected G-CSF use for 5 consecutive days or more

Provider Actions and Billing Requirements

Prior Authorization

Submit clinical documentation for medical necessity

The treating provider must submit clinical evidence that the member meets the criteria for treatment. EmblemHealth will not review the request (preauthorization or post-payment) without this documentation.

Step Therapy

Step therapy requirement

Member must fail trial of Neulasta AND Udenyca prior to initiating Ziextenzo. Requesting provider should supply justification or evidence if claiming a contraindication to these agents.

Commercial, Medicaid, and Medicare members are subject to step therapy and require prior trial of Neulasta and Udenyca or documented contraindication/justification.

Applicable Codes

Applicable Procedure Codes (HCPCS/Q-code)HCPCSCovered

Q5120

Injection, pegfilgrastim-bmez, biosimilar, (Ziextenzo) 1 billable unit. Effective Date: 07/01/2020

Applicable NDCsNDCCovered

61314-0866-01

Ziextenzo 6 mg prefilled syringe

Applicable ICD-10 Diagnoses (examples listed)ICD-10

D70.1	Agranulocytosis secondary to cancer chemotherapy
D70.9	Neutropenia, unspecified
T45.1XSS	Adverse effect of antineoplastic and immunosuppressive drugs sequela
T45.1XSA	Adverse effect of antineoplastic and immunosuppressive drugs initial encounter
T45.1XSD	Adverse effect of antineoplastic and immunosuppressive drugs subsequent encounter
Z51.11	Encounter for antineoplastic chemotherapy (policy lists 251.11 which appears to be a typographic error)
Z51.12	Encounter for antineoplastic immunotherapy
Z48.21	Encounter for aftercare following bone marrow transplant (policy contains several numeric typos such as 248.290 etc.)
Z52.091	Other blood donor, stem cells (policy lists ZZ52.091 which appears to be a typographic error)
Z94.81	Bone marrow transplant status (policy lists 294.81 etc. — included as mapping for transplant status mentions)

Coding caveats: the policy notes that the previously used J-code was deleted and the Q-code Q5120 (Injection, pegfilgrastim-bmez; 1 billable unit) was added, effective 07/01/2020. The revision history documents deletion of a J-code and addition of Q5120. Also, the policy's ICD-10 listings in the source contain typographic/numeric errors (for example policy text lists values such as 251.11, 248.290, ZZ52.091, 294.81); coders should map these to the correct ICD-10 codes shown elsewhere in the policy (for example Z51.11, Z48.21, Z52.091, Z94.81) when assigning diagnoses.

Background and Clinical Context

Rationale and background: Ziextenzo is a pegylated filgrastim biosimilar that stimulates hematopoietic cells and is used prophylactically to reduce febrile neutropenia in patients receiving myelosuppressive chemotherapy; the policy bases coverage criteria on clinical literature, evidence-based guidelines, and regulatory status. The policy includes dosing constraints (standard dose 6 mg subcutaneously per chemotherapy no more frequently than every 14 days, and acute radiation exposure dosing 6 mg weekly for 2 doses) and maps doses to billable units (policy mapping: 6 mg = 12 billable units). EmblemHealth’s guideline language clarifies that individual benefit programs and legal requirements (including CMS for Medicare/Medicaid members) govern coverage, and treating providers must submit clinical documentation for medical necessity; step therapy requiring prior trials of Neulasta and Udenyca for Ziextenzo initiation is noted for applicable members.

Revision History

2025-03-20revisedLatest

Updated risk factors (patient co-morbidities) for febrile neutropenia and added criterion: patients with expected febrile neutropenia <10% AND two or more patient-related risk factors; separated co-morbidities from criteria and created a chart reference.

2024-03-21revised

Annual Review: Updated dosing limits and dose chart.

2023-09-15removed

Deleted J code J3590 from applicable procedure codes.