CurrentCareSourcePolicy N/A

Oncology (Injectable) Levoleucovorin Products Utilization Management Medical Policy

Defines prior authorization and coverage criteria for levoleucovorin injectable products (Fusilev, Khapzory, generics) for oncology and methotrexate rescue indications affecting prescribers and payers under CareSource in North Carolina.

Policy Summary

PayerCareSource

PolicyOncology (Injectable) Levoleucovorin Products Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateJun 26, 2024

Key ActionObtain prior authorization and document prescriber consultation and indication aligned with criteria (oncologist involvement required for cancer indications).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA groups

1 mo / 1 yrTypical durations

Prior AuthAuthorization

NCCNCompendia

Coverage and Authorization Criteria

FDA‑Approved Indications

Policy Summary

PayerCareSource

PolicyOncology (Injectable) Levoleucovorin Products Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateJun 26, 2024

Key ActionObtain prior authorization and document prescriber consultation and indication aligned with criteria (oncologist involvement required for cancer indications).

SourceLink

On This Page

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Colon or Rectal Carcinoma (FDA): A) Levoleucovorin is used in combination with fluorouracil-based chemotherapy; AND B) Levoleucovorin is prescribed by or in consultation with an oncologist.Approve for 1 year

Dosing: Approve up to 200 mg IV administered before each dose of 5-fluorouracil (as written).

Methotrexate Overdosage or Impaired Methotrexate Elimination (FDA): Levoleucovorin is used for methotrexate overdosage or impaired methotrexate elimination.Approve for 1 month

Approve ONE of the following dosing regimens: A) Administer up to 7.5 mg IV no more frequently than once every 6 hours; OR B) Administer up to 75 mg IV no more frequently than once every 3 hours.

Osteosarcoma (FDA): A) Levoleucovorin is used in combination with high‑dose methotrexate; AND B) Levoleucovorin is prescribed by or in consultation with an oncologist.Approve for 1 year

Approve ONE of the following dosing regimens: A) Administer up to 7.5 mg IV no more frequently than once every 6 hours; OR B) Administer up to 75 mg IV no more frequently than once every 3 hours.

Other Uses with Supportive Evidence (NCCN/compendium)

Covered when ALL of the following are met for other supported oncology uses

Cancer diagnosis currently being treated with methotrexate (NCCN/Compendium): Levoleucovorin is prescribed by or in consultation with an oncologist for a cancer diagnosis currently being treated with methotrexate.Approve for 1 year

Approve ONE of the following dosing regimens: Administer up to 7.5 mg IV no more frequently than once every 6 hours; OR administer up to 75 mg IV no more frequently than once every 3 hours.

Cancer diagnosis currently being treated with 5‑fluorouracil (NCCN/Compendium): Levoleucovorin is prescribed by or in consultation with an oncologist and administered intravenously before each dose of 5‑fluorouracil.Approve for 1 year

Examples cited in compendium include ovarian, gastric, and cervical cancers and multiple other tumor types per NCCN.

Recommended Regimens and Dosing

Regimen	Indication / Context	Dosing (document text)	Coverage
Levoleucovorin administered IV prior to 5‑fluorouracil
Adjunct to 5‑fluorouracil–based chemotherapy (e.g., colon or rectal carcinoma; other cancers per NCCN), prescribed by or in consultation with an oncologist
Approve up to 200 mg administered intravenously before each dose of 5‑fluorouracil (as written in document)
Covered when criteria met (approve for 1 year for FDA‑approved colorectal indication)

Regimen	Indication / Context	Dosing (document text)	Coverage
Levoleucovorin for rescue after high‑dose methotrexate or methotrexate overdose/impaired elimination
Methotrexate overdosage or impaired methotrexate elimination; also used for cancers being treated with methotrexate (per supportive evidence)
Approve ONE of the following: A) Administer up to 7.5 mg IV no more frequently than once every 6 hours; OR B) Administer up to 75 mg IV no more frequently than once every 3 hours (document text)
Covered when criteria met (approve for 1 month for methotrexate overdosage; 1 year for cancer indications when supported)

Product References and Dosing Details

Referenced productsNDC

NDCs not listed

Levoleucovorin intravenous infusion products (Fusilev, Khapzory, generics) referenced but no NDCs provided in document

inv-06: Dosing frequency thresholds — methotrexate rescue and pre‑5‑FU dosing

Methotrexate rescue — lower-frequency optionAdminister up to 7.5 mg IV no more frequently than every 6 hours

Methotrexate rescue — higher-dose optionAdminister up to 75 mg IV no more frequently than once every 3 hours

5‑Fluorouracil combination (pre‑5‑FU dosing)Approve up to 200 mg IV administered before each dose of 5‑fluorouracil (as written in document)

Prior Authorization and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is recommended for medical benefit coverage of levoleucovorin. Approvals are provided for the durations specified in the Recommended Authorization Criteria (for example, 1 year for approved cancer indications and 1 month for methotrexate overdosage). Requests for doses outside the dosing regimens documented in this policy will be considered on a case-by-case basis by a clinician (e.g., Medical Director or Pharmacist).

All approvals are provided for the duration noted in the policy; when duration is expressed in months, 1 month = 30 days.
Levoleucovorin should be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., an oncologist for cancer indications).
No automation is available for prior authorization.

Documentation Required

Prescriber and Indication Documentation

Providers must document the prescriber specialty and the indication for use when submitting requests for levoleucovorin. For cancer and other oncology-related indications, levoleucovorin must be prescribed by or in consultation with an oncologist and supporting documentation (e.g., treatment plan, chemotherapy regimen including fluorouracil or methotrexate use, and relevant diagnosis) should be included with the request.

Applicable to FDA-approved indications and Other Uses with Supportive Evidence (e.g., cancer diagnoses treated with methotrexate or 5‑fluorouracil).
Include dosing regimen and frequency per the policy dosing tables.
For methotrexate overdosage, include details of the methotrexate event and justification for rescue therapy.

Denial Risk

Denial Risk — Non‑recommended Uses

Requests for levoleucovorin that are for circumstances not listed in the Recommended Authorization Criteria are not recommended for approval.

The Recommended Authorization Criteria include FDA‑approved indications and other uses with supportive evidence as specified in the policy.
Criteria will be updated as new published data become available.

Key Terms and Drug Definition

inv-12: Levoleucovorin — definition and context

DefinitionLevoleucovorin is the pharmacologically active levo‑isomer of racemic d,l‑leucovorin; a reduced folate used to counteract toxicity of folic acid antagonists and to modulate fluoropyrimidine therapy.

Clinical roleUsed to rescue patients after high‑dose methotrexate or impaired methotrexate elimination and as an adjunct to 5‑fluorouracil–based chemotherapy (e.g., colorectal cancer).

Examples of indicationsImpaired methotrexate elimination/overdosage and osteosarcoma (rescue), and combination use with 5‑FU for colorectal and other cancers.

Clinical Background

Levoleucovorin is the pharmacologically active levo‑isomer of leucovorin, a reduced folate that serves two principal roles in oncology: to rescue normal cells from the toxic effects of folic acid antagonists such as methotrexate, and to modulate or enhance the antitumor activity of fluoropyrimidine agents (for example, 5‑fluorouracil). It is indicated as an adjunct to fluorouracil‑based chemotherapy for colorectal cancer and certain other tumors, and as a rescue agent after high‑dose methotrexate or in cases of methotrexate overdose or impaired elimination. For coverage purposes, dosing examples cited in the policy include regimens such as up to 7.5 mg IV every 6 hours or up to 75 mg IV every 3 hours for methotrexate rescue, and up to 200 mg IV before each 5‑FU dose when used with fluorouracil, consistent with the document’s clinical context and labeled uses.

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