ModifiedEmblemHealthPolicy MG.MM.PH.83

levoleucovorin (Fusilev) injection — coverage and prior authorization criteria

Clinical coverage and prior authorization criteria for intravenous levoleucovorin (Fusilev) when used as rescue therapy with methotrexate or in combination with fluorouracil, and for treatment of listed malignancies; applies to EmblemHealth members and providers requesting coverage.

Policy Summary

PayerEmblemHealth

Policylevoleucovorin (Fusilev) injection — coverage and prior authorization criteria

Policy CodePolicy MG.MM.PH.83

Change TypeMaterial updates to indications and NDCauthorization period adjusted

Effective Date

Next Review DateMar 1, 2024

Key ActionSubmit clinical evidence that the member meets the listed initial approval criteria when requesting prior authorization, including documentation of indication and regimen.

SourceLink

POLICY UPDATE CHANGES

Added NDC: 72893-0009-01 to the policy's initial criteria.

Initial criteria updated to include use in combination with high-dose methotrexate for Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma (for symptomatic Bing-Neel syndrome) and removed Follicular Lymphoma.

Added 'Ampullary Adenocarcinoma and Cervical Cancer' as indications when used with fluorouracil-based regimens.

Length of authorization changed from 6 months to 90 days.

90 daysinitial authorization length

≥6 yrsminimum patient age

1,200max units (methotrexate/overdose)

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Coverage Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met (depending on indication group):

General eligibility: Patient is at least 6 years old; patient does not have pernicious anemia or vitamin B12 deficiency megaloblastic anemia; racemic d,l-leucovorin calcium is not obtainable (in any dosage strength) as confirmed by FDA Drug shortage resources.age >= 6 years

From general initial approval criteria

High-dose methotrexate rescue: Patient is undergoing high-dose methotrexate chemotherapy and levoleucovorin will be used as rescue therapy in combination with a chemotherapy regimen containing high-dose methotrexate.

Indications list includes specific malignancies for use with high-dose methotrexate

Toxicity/overdose management: Patient is undergoing treatment with a folic acid antagonist (e.g., methotrexate) and has developed toxicity due to impaired elimination or inadvertent overdosage.

Overdose/rescue indication

Fluorouracil combination: Must be used in combination with fluorouracil-based regimens for listed malignancies.

Fluorouracil-modulated indications

inv-03: Initial Therapy / Indications (partial)

Covered when used as specified in combination regimens or for listed malignancies per initial criteria

Indications list (regimen-specific): Policy lists multiple malignancies where levoleucovorin is used either in combination with high-dose methotrexate or with fluorouracil-based regimens; recent additions include Ampullary Adenocarcinoma, Cervical Cancer, and Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma (for symptomatic Bing-Neel syndrome).

See full indications lists for mapping of specific diagnoses to high-dose methotrexate vs fluorouracil combinations.

inv-02: Continuation Therapy / Renewal

Coverage may be renewed when ALL of the following are met:

Continuation requirements: Patient continues to meet initial approval criteria; racemic d,l-leucovorin calcium is not obtainable (in any dosage strength) as confirmed by the FDA Drug shortage website; absence of unacceptable toxicity (examples include hypersensitivity reactions, seizures, severe gastrointestinal disorders such as stomatitis, severe diarrhea, or severe nausea/vomiting).

Renewal conditions

Coverage for levoleucovorin (Fusilev) is limited to the indications listed in this policy. Fusilev is considered investigational when used for any indication not listed in the policy, and requests for uses outside the documented indications will not meet medical necessity criteria.

The policy’s indication list was revised effective 3/1/2024. As part of that revision, Follicular Lymphoma was removed from the list of indications for use with high‑dose methotrexate in this policy.

No additional non‑covered or not medically necessary uses are explicitly stated in the provided policy excerpts beyond the investigational exclusion for indications not listed in the policy and the changes noted in the revision history.

Initial Therapy Criteria

inv-26: Initial Therapy

Initial approval requirements

General initial criteria: Patient is at least 6 years old; no pernicious anemia or vitamin B12 deficiency megaloblastic anemia; racemic d,l-leucovorin calcium is not obtainable in any dosage strength.

Indication: high-dose methotrexate rescue: Patient is undergoing high-dose methotrexate chemotherapy and levoleucovorin will be used as rescue therapy in combination with a chemotherapy regimen containing high-dose methotrexate.

Indication: management of toxicity/overdose: Patient is receiving a folic acid antagonist (e.g., methotrexate) and has developed toxicity due to impaired elimination or inadvertent overdosage.

Indication: fluorouracil-modulated therapy:

Continuation / Renewal Criteria

inv-28: Renewal

Renewal conditions and requirements

Renewal: Patient continues to meet initial approval criteria; racemic d,l-leucovorin calcium is not obtainable (any strength) per FDA Drug shortage website; absence of unacceptable toxicity (e.g., hypersensitivity, seizures, severe GI disorders).

Documentation at renewal: Provider must submit clinical evidence that the patient continues to meet the initial criteria and document the specific cancer indication and regimen (e.g., combination with high‑dose methotrexate or fluorouracil‑based regimens).

Lack of submitted clinical evidence may lead to denial.

Coding and Quantity Limits

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Coverage is provided only when the listed initial approval criteria in the policy are met.

Prior authorization required for requests for racemic d,l-leucovorin calcium (Fusilev) per policy MG.MM.PH.83.
NDC 72893-0009-01 is included in the policy's drug list per recent revision history.

Documentation Required

Clinical Evidence Submission Required

The treating clinician must submit the clinical evidence that the member meets the requested treatment criteria. Without this documentation EmblemHealth will not be able to properly review the request (preauthorization or post-payment review).

Submit clinical records demonstrating the specific cancer indication and the regimen planned (e.g., combination with high-dose methotrexate or fluorouracil-based regimens).
Document member age (must be ≥ 6 years), absence of pernicious anemia or vitamin B12 deficiency–related megaloblastic anemia, and confirmation that racemic d,l-leucovorin calcium is not obtainable when applicable.

Background

Levoleucovorin (levoleucovorin calcium, marketed as Fusilev) is a folinic acid analog used primarily as a rescue agent following high‑dose methotrexate chemotherapy to reduce toxicity and rescue normal cells. It is also used to modulate the activity and reduce toxicity of fluorouracil when given in combination with fluorouracil‑based regimens, and for treatment of specific malignancies per the policy when used in the regimen contexts described.

Definitions

Rescue therapy / leucovorin rescue — Definition and context

DefinitionRescue therapy: administration of levoleucovorin to reduce toxicity or rescue normal cells from folic acid antagonist effects (e.g., following high-dose methotrexate)

Clinical contextUsed when patient is undergoing high-dose methotrexate chemotherapy and levoleucovorin will be used as rescue therapy within the chemotherapy regimen

Overdose indicationUsed to manage toxicity due to impaired elimination or inadvertent overdosage of folic acid antagonists (e.g., methotrexate)

levoleucovorin (Fusilev) — Package insert reference

ReferenceFusilev [package insert]: Spectrum Pharmaceuticals, Inc; April 2011. Accessed December 2019.

Use in policy documentationPackage insert is cited in policy references for clinical context and dosing guidance

Revision History

2024-03-01annual_review/material_changeLatest

Annual review: added NDC 72893-0009-01 to the policy initial criteria; initial criteria revised to remove Follicular Lymphoma and add Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma (for symptomatic Bing‑Neel syndrome); added Ampullary Adenocarcinoma and Cervical Cancer to fluorouracil‑based regimen indications.

2023-06-29revision/clinical_criteria

Added Ampullary Adenocarcinoma and Cervical Cancer to indications for use with fluorouracil‑based regimens; updated multiple colorectal and hematologic indication listings and removed Adult T‑cell Leukemia/Lymphoma in one entry; shortened length of authorization from 6 months to 90 days.