CurrentCareSourcePolicy N/A

Levoleucovorin (injectable) utilization management

Defines prior authorization, coverage criteria, dosing, and allowed indications for intravenous levoleucovorin products (Fusilev, Khapzory, generics) for oncology and methotrexate rescue indications affecting providers who prescribe or administer these agents.

Policy Summary

PayerCareSource

PolicyLevoleucovorin (injectable) utilization management

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateJun 26, 2024

Key ActionObtain prior authorization and document indication, dosing, prescriber specialty (oncologist), and duration consistent with the policy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA‑approved indication groups

1 yrTypical oncology approval

1 moMethotrexate rescue approval

NCApplicable state

Recommended Authorization Criteria

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Colon or Rectal Carcinoma (with 5‑FU)

Levoleucovorin is prescribed by or in consultation with an oncologist.

Methotrexate Overdosage or Impaired Methotrexate Elimination: Levoleucovorin is used for methotrexate overdosage or impaired methotrexate elimination.

Approve for 1 month; dosing: approve ONE of the following regimens: (A) up to 7.5 mg IV no more frequently than every 6 hours OR (B) up to 75 mg IV no more frequently than every 3 hours.

Osteosarcoma (high‑dose methotrexate rescue)

Levoleucovorin is prescribed by or in consultation with an oncologist.

inv-02: Other Uses with Supportive Evidence

Other uses with supportive evidence (coverage recommended when criteria met):

Cancer diagnosis currently being treated with methotrexate: Levoleucovorin is prescribed by or in consultation with an oncologist for a malignancy being treated with methotrexate (note: includes CNS cancers per policy note).

Approve for 1 year; dosing: approve ONE of the following regimens: (A) up to 7.5 mg IV no more frequently than every 6 hours OR (B) up to 75 mg IV no more frequently than every 3 hours.

Cancer diagnosis currently being treated with 5‑fluorouracil: Levoleucovorin is prescribed by or in consultation with an oncologist and is administered intravenously before each dose of 5‑fluorouracil.

Approve for 1 year; dosing: administered IV prior to each 5‑FU dose (policy gives example dosing; see dosing for 5‑FU combination).

Dosing and Administration Regimens

Regimen	Dosing / Timing	Coverage Status
Levoleucovorin administered IV before each dose of 5‑fluorouracil (used in combination with fluorouracil‑based chemotherapy)
Approve up to 200 mg IV administered before each dose of 5‑fluorouracil
Covered when used as described for colon/rectal carcinoma or other fluorouracil‑containing regimens per policy and NCCN guidance

inv-11: informational — Line of Therapy criteria

Line of therapy: Used as part of combination chemotherapy with 5‑fluorouracil for colon/rectal cancer or as rescue after high‑dose methotrexate; policy does not specify first‑line versus later‑line beyond these indications.

Informational only.

Prior Authorization, Documentation, and Billing Guidance

Prior Authorization

Prior authorization required for levoleucovorin

Prior authorization is recommended for medical benefit coverage of levoleucovorin; approval is recommended when the patient meets the policy's specified criteria and dosing for the listed indications. Extended approvals are allowed if the patient continues to meet the Criteria and Dosing; requests for doses outside the established dosing will be considered case-by-case by a clinician.

Approvals are provided for the duration noted in the policy (e.g., 1 year for most oncology indications, 1 month for methotrexate overdosage/impaired elimination).

Step Therapy

Step therapy

No step therapy requirements are specified in this policy.

Documentation Required

Prescriber and documentation requirements

Prior authorization is recommended; levoleucovorin must be prescribed by or in consultation with an oncologist for the listed oncology indications, and dosing, indication, and duration must be documented consistent with the policy.

For colon/rectal carcinoma and osteosarcoma: prescriber is or consults an oncologist (chunk 5).
For other uses treated with methotrexate or 5‑FU: prescriber is or consults an oncologist (chunk 6).

Denial Risk

Non‑listed indications may be denied

Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria; requests for indications outside the policy may be denied.

Criteria will be updated as new published data become available.

Clinical Background

Levoleucovorin is the pharmacologically active levo‑isomer of racemic leucovorin and is a reduced derivative of folic acid. It is used to counteract toxic effects of folic acid antagonists (e.g., methotrexate) and to enhance the activity of fluoropyrimidines such as 5‑fluorouracil. Indications include use with 5‑FU for colorectal cancer, rescue after high‑dose methotrexate in osteosarcoma, and treatment of impaired methotrexate elimination or overdose.

Key Definitions

Levoleucovorin — definition and short description

Generic nameLevoleucovorin (levo‑isomer of racemic d,l‑leucovorin)

Pharmacologic descriptionThe pharmacologically active, levo‑isomer of racemic d,l‑leucovorin; a reduced derivative of folic acid.

Primary actionsCan counteract toxic and therapeutic effects of folic acid antagonists (e.g., methotrexate) and can enhance the therapeutic effects of fluoropyrimidines (e.g., 5‑fluorouracil).

Common brand names (examples)Fusilev, Khapzory, and generics

Typical oncologic usesUsed with 5‑fluorouracil for colorectal cancer; rescue after high‑dose methotrexate for osteosarcoma; treatment of impaired methotrexate elimination or overdose.