CurrentmhnPolicy CP.PHAR.393

Leucovorin Injection

Defines medical necessity, prior-authorization and coverage criteria for leucovorin injection for Commercial and Medicaid lines of business administered by Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyLeucovorin Injection

Policy CodePolicy CP.PHAR.393

Change TypeNo material changes

Effective DateDec 1, 2018

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

4Covered indication groups (MTX rescue/toxicity, megaloblastic anemia, 5-FU combination, Other)

J0640HCPCS code listed for leucovorin (per 50 mg)

1 mg/dayMaximum daily dose for megaloblastic anemia

VariableApproval durations differ by indication and line of business

Medical Necessity Criteria for Leucovorin Injection

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A. Methotrexate/Folic Acid Antagonist Toxicity Prophylaxis (Rescue/Antidote)

1. Indication
- Rescue after high-dose methotrexate therapy for osteosarcoma or an NCCN-recommended cancer (see Appendix D)
- Antidote for impaired methotrexate (MTX) elimination
- Antidote for accidental overdose of folic acid antagonists (including MTX)
2. Dosing/regimen support
- Dose is appropriate and will be adjusted as necessary per section V (dosage and administration)
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant use (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN
marked with * in policy

B. Megaloblastic Anemia

Diagnosis of megaloblastic anemia due to folic acid deficiency
Member is not a candidate for oral folic acid therapy
Dose does not exceed 1 mg per day

C. Combination Chemotherapy with 5-FU

Prescribed for use in a fluorouracil-based chemotherapy treatment regimen for colorectal cancer or an NCCN-recommended cancer (see Appendix D)
Prescribed by or in consultation with an oncologist
Prescribed in combination with 5-FU
Dose support
- For colorectal cancer: dose does not exceed regimen in section V
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant use (prescriber must submit supporting evidence)

D. Other diagnoses/indications

If drug label recently changed within last 6 months and not reflected, follow formulary/nonformulary/no-coverage policies referenced
If requested use is not listed in Section III and criterion 1 above does not apply, refer to off-label use policies referenced

Continued (Renewal) Therapy Criteria

Coverage continuation requirements for ongoing therapy vary by indication:

A. Megaloblastic Anemia continued therapy

ANY of the following
- Member currently receiving medication via Centene benefit or previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (see state addendums CC.PHARM.03A/03B)
Member is not a candidate for oral folic acid therapy
Member is responding positively to therapy
If dose increase requested, new dose does not exceed 1 mg per day

B. All other indications (continued therapy)

ANY of the following
- Member currently receiving medication via Centene benefit or previously met initial approval criteria
- Member currently receiving medication and enrolled in state/product with continuity of care regulations (see CC.PHARM.03A/03B)
- Documentation shows member is receiving requested drug for high-dose MTX rescue as part of chemotherapy or combination chemotherapy with 5-FU and has received medication for at least 30 days
Member is responding positively to therapy
ANY of the following
- If request is for dose increase, new dose does not exceed regimen in section V

C. Other diagnoses/indications (continued therapy)

Refer to formulary/nonformulary/no-coverage or off-label policies as in Initial section if use not specifically listed

What Providers Must Do

Prior Authorization

Prior authorization required per policy

Requests for leucovorin injection are subject to prior authorization and must meet the policy's indication-specific criteria and dosing/regimen support (FDA‑approved or NCCN‑recommended).

Affected code: J0640 (Injection, leucovorin calcium, per 50 mg)
Requests must meet the listed indication-specific criteria (see Section I) and dosing/regimen support (FDA‑approved regimen or NCCN recommendation).

Documentation Required

Submit supporting clinical documentation

Provider must submit documentation supporting that the member meets all approval criteria.

Office chart notes documenting indication and prescribing clinician (e.g., oncologist consultation for 5‑FU combinations)
Relevant laboratory results (e.g., serum methotrexate levels for high‑dose MTX rescue, creatinine changes)
Other clinical information demonstrating response to therapy or why oral folic acid is not feasible

Documentation Required

Dose justification for non-standard regimens

If the requested dose exceeds the standard regimens described in Section V, the prescriber must provide supporting evidence that the higher dose is appropriate.

Provide practice guideline recommendations or peer‑reviewed literature that support the non‑standard dosing regimen
Documentation should reference the specific regimen in Section V (e.g., high‑dose MTX rescue or advanced colorectal cancer regimens) and rationale for deviation

Step Therapy

Formulary/nonformulary routing for non-listed indications

If the requested indication or dosing is not listed in Section III/I (or a recent label change applies), follow the referenced formulary/nonformulary or off‑label routing policies.

Follow no coverage/nonformulary policies: CP.CPA.190 (Commercial) and CP.PMN.255 (Medicaid)
Follow nonformulary policy for drugs not on PDL: CP.PMN.16 (Medicaid) or CP.CPA.190 (Commercial)
For off‑label uses not listed, follow off‑label use policies: CP.CPA.09 (Commercial) and CP.PMN.53 (Medicaid)

Clinical Thresholds and Laboratory Criteria

Thresholds

Megaloblastic anemia dose limit<= 1 mg per day

High-dose MTX rescue lab threshold to stop rescueserum MTX < 5 x 10^-8 M (0.05 μM)

Normal MTX elimination reference levelsserum MTX 10 μM at 24h, 1 μM at 48h, <0.2 μM at 72h

Delayed late MTX eliminationserum MTX >0.2 μM at 72h and >0.05 μM at 96h

Delayed early MTX elimination / renal injuryserum MTX ≥50 μM at 24h, ≥5 μM at 48h, or ≥100% increase in serum creatinine at 24h

Clinical and Administrative Background

Leucovorin is a reduced folate with multiple clinical uses. It is indicated as a rescue agent after high‑dose methotrexate (MTX) therapy, and dosing for MTX rescue is tailored to MTX levels and clinical response with regimens that continue until serum MTX falls below specified thresholds (stop rescue when MTX < 5 x 10^-8 M (0.05 μM)).

Leucovorin is also an antidote for impaired MTX elimination or for inadvertent overdose of folic acid antagonists, with recommended dosing and escalation based on MTX concentrations and renal function to reduce toxicity.

For hematologic indications, leucovorin is indicated for the treatment of megaloblastic anemia due to folic acid deficiency when oral therapy is not feasible; the injectable regimen is limited to a maximum of 1 mg per day intravenously or intramuscularly.

In oncology, leucovorin is used in combination with 5‑fluorouracil (5‑FU) to prolong survival in the palliative treatment of advanced colorectal cancer, with specific IV dosing regimens recommended when given with 5‑FU.

Policy Summary

Payermhn

PolicyLeucovorin Injection

Policy CodePolicy CP.PHAR.393

Change TypeNo material changes

Effective DateDec 1, 2018

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that member meets all approval criteria.

SourceLink

On This Page

OpenPayer

Leucovorin Injection

Medical Necessity Criteria for Leucovorin Injection

Codes and Billing

What Providers Must Do

Clinical Thresholds and Laboratory Criteria

Clinical and Administrative Background

Defined Terms

Scope, Status and Review Dates

Leucovorin Injection

Medical Necessity Criteria for Leucovorin Injection

Codes and Billing

What Providers Must Do

Clinical Thresholds and Laboratory Criteria

Clinical and Administrative Background

Defined Terms

Policies to Read With This One

Scope, Status and Review Dates