Centene Leucovorin Injection Coverage

Coverage Criteria

Initial Therapy

Covered when ALL of the following per selected indication are met

Indication choice: Prescribed for one of the following uses: rescue after methotrexate (MTX) therapy for osteosarcoma or an NCCN-recommended cancer; antidote for impaired MTX elimination; antidote for accidental overdose of folic acid antagonists (including MTX); treatment of megaloblastic anemia due to folic acid deficiency when oral therapy is not feasible; use in combination with fluorouracil (5-FU)–based chemotherapy for colorectal cancer or other NCCN-recommended cancers.

Refer to Appendix D for NCCN-recommended cancers.

Methotrexate/Folic Acid Antagonist Toxicity Prophylaxis: When used as rescue after MTX therapy or for impaired MTX elimination: dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); dose is appropriate and will be adjusted per section V; prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval durations vary by indication (see policy): impaired elimination/accidental overdose: 1 month; high‑dose MTX rescue: typically up to 6 months.

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.<= 1 mg/day

Leucovorin is contraindicated for pernicious anemia and other B12‑deficiency megaloblastic anemias.

Combination chemotherapy with 5-FU: Prescribed for use in a fluorouracil‑based chemotherapy regimen for colorectal cancer or an NCCN‑recommended cancer; prescribed in combination with 5‑FU; prescribed by or in consultation with an oncologist; dose does not exceed the regimen limits in section V and is supported by guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); regimen must be FDA‑approved or recommended by NCCN.

Examples of recommended regimens are provided in section V (e.g., 20–200 mg IV per regimen specifications).

Continued Therapy

Covered when ALL of the following for continued therapy are met

Continuation eligibility: Member is currently receiving leucovorin via the Centene benefit OR has previously met initial approval criteria OR is enrolled in a state/product with continuity of care regulations.

Refer to state specific addendums for continuity of care details.

Response and dosing: Member is responding positively to therapy; if the request is for a dose increase, the new dose must not exceed indication‑specific maximums (for example, megaloblastic anemia ≤ 1 mg/day) or regimen limits in section V.

For dose increases, prescriber must submit supporting evidence if dose exceeds standard regimen limits.

High-dose methotrexate rescue

Covered when ALL of the following are met

High-dose MTX rescue criteria: Patient received high‑dose methotrexate and requires leucovorin rescue.

Standard leucovorin rescue: 15 mg PO/IV/IM every 6 hours for 10 doses starting 24 hours after start of MTX infusion for normal elimination; continue until serum MTX < 0.05 μM. For delayed elimination or acute renal injury, intensify to 150 mg IV every 3 hours until MTX < 0.05 μM per protocol. Prescriber must adjust or extend rescue based on clinical situation and laboratory findings.

Leucovorin with fluorouracil

Covered when ALL of the following are met

Leucovorin with 5-FU regimens: Leucovorin is used as a modulator with fluorouracil‑based regimens (e.g., advanced colorectal cancer) per recommended regimens: examples include 200 mg IV slow injection followed by 5‑FU, or 20 mg IV followed by 5‑FU; typical 5‑day courses may be repeated every 28 days as specified by the regimen.

Prescribed regimen must be FDA‑approved or recommended by NCCN; prescriber must submit supporting evidence when dose deviates from regimen limits in section V.

Megaloblastic anemia

Covered when ALL of the following are met

Megaloblastic anemia due to folate deficiency: Patient has documented megaloblastic anemia due to folate (folic acid) deficiency; patient is not a candidate for oral folic acid therapy; dosing up to 1 mg IV or IM once daily.<= 1 mg/day

Leucovorin is contraindicated for pernicious anemia and other megaloblastic anemias secondary to vitamin B12 deficiency because hematologic remission may mask ongoing neurologic progression.

Coverage for uses of leucovorin that are not specifically addressed in this policy is not authorized unless the provider submits sufficient clinical documentation demonstrating efficacy and safety in accordance with Centene off‑label use requirements. For non‑FDA approved indications, follow the payer’s off‑label use policies (CP.CPA.09 for commercial lines and CP.PMN.53 for Medicaid) or applicable evidence‑of‑coverage documentation when requesting authorization.

Leucovorin is contraindicated for the treatment of pernicious anemia and other megaloblastic anemias caused by cobalamin (vitamin B12) deficiency. Hematologic parameters may improve with folate administration while neurologic damage continues to progress; therefore leucovorin is improper therapy in these conditions and should not be used.

Initial Therapy

Initial therapy coverage requires meeting indication-specific criteria and dosing limits

General: Prescribed regimen must be FDA‑approved or recommended by NCCN; when dose is supported by practice guidelines or peer‑reviewed literature, prescriber must submit supporting evidence; dose must be appropriate and adjustable per section V.

Approval durations: impaired elimination/accidental overdose: 1 month; high‑dose MTX rescue: up to 6 months (commercial and Medicaid as specified).

Initial therapy dosing

Initial dosing depends on indication

Initial dosing examples: Rescue after high‑dose MTX: 15 mg PO/IV/IM every 6 hours for 10 doses starting 24 hours after MTX infusion (continue until serum MTX < 0.05 μM). For delayed elimination or renal injury: 150 mg IV every 3 hours until MTX < 0.05 μM. Megaloblastic anemia: up to 1 mg IV or IM once daily. Advanced colorectal cancer regimens: leucovorin 20–200 mg IV per regimen specifications.

Adjust dosing per laboratory monitoring and prescriber protocol.

Continuation Criteria

Continuation Therapy

Continuation coverage requires current therapy or prior approval and clinical benefit

Continuation criteria: Member is currently receiving leucovorin via Centene benefit OR previously met initial approval criteria OR is enrolled in a state/product with continuity of care regulations; member is responding positively to therapy; dose increases must meet indication‑specific limits.

For dose increases, request must meet regimen limits in section V and supporting evidence if applicable.

Continuation therapy — MTX rescue

Continue leucovorin rescue until laboratory thresholds are met

Continuation until MTX clearance: Continue leucovorin administration until serum methotrexate (MTX) is < 0.05 μM; adjust or extend rescue based on clinical situation and laboratory findings.MTX < 0.05 μM

For delayed elimination or acute renal injury, use intensified IV dosing (e.g., 150 mg IV every 3 hours) until MTX clearance is achieved.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must demonstrate the prescribed use meets the policy's specified indications and dosing criteria, and include supporting evidence when requested (e.g., practice guidelines or peer‑reviewed literature for nonstandard dosing). Approval durations vary by indication (see policy).

Prior authorization must document that the indication matches the criteria in the policy (e.g., rescue after high‑dose methotrexate, impaired methotrexate elimination, inadvertent overdose, megaloblastic anemia, or other approved indications).
Dose must be supported by FDA labeling, NCCN recommendations, or peer‑reviewed literature when applicable; prescriber must submit supporting evidence for nonstandard regimens.

Billing Rule

Billing / Coding Requirement

Claims for injectable leucovorin should be billed using the HCPCS code below. Providers must follow payer coding and billing guidance when submitting claims.

Coding

HCPCS Codes referencedHCPCS

J0640

Injection, leucovorin calcium, per 50 mg

inv-09: Serum methotrexate level threshold for stopping rescue

Serum MTX level to stop rescue< 0.05 μm (MTX level below 5 x 10^-8 M)

Continuation ruleContinue leucovorin until serum MTX < 0.05 μm

Reference contextRescue after high-dose MTX: 15 mg every 6 hours for 10 doses starting 24 hours after infusion; extend until MTX < 0.05 μm

inv-10: Delayed elimination triggers high-dose regimen

Delayed elimination MTX thresholds24-hour MTX > 5 x 10^-6 M OR 48-hour MTX > 9 x 10^-7 M

Creatinine triggerIncrease in serum creatinine ≥ 50% at 24 hours over baseline

Definitions

inv-20: 5-FU — abbreviation definition

Abbreviation5-FU = 5-fluorouracil

Usage noteReferenced in appendices and dosing regimens where leucovorin is used as a modulator with 5-fluorouracil

ContextUsed in fluorouracil-based chemotherapy regimens (e.g., advanced colorectal cancer)

inv-21: MTX — abbreviation definition

AbbreviationMTX = methotrexate

Usage noteMTX referenced throughout for high-dose therapy requiring leucovorin rescue

Context

Background

Leucovorin (folinic acid, reduced folate) is used clinically to mitigate toxicity from folic acid antagonists and to rescue patients after high‑dose methotrexate (MTX) therapy. For standard MTX rescue, the protocol is 15 mg PO/IV/IM every 6 hours for 10 doses starting 24 hours after the start of the MTX infusion, continuing until serum MTX is 0.05 μM. In cases of delayed MTX elimination or acute renal injury, intensified IV dosing (for example, 150 mg IV every 3 hours per protocol) is used until MTX clearance is achieved. Leucovorin is also employed as a biochemical modulator when given with 5‑fluorouracil (5‑FU) in certain chemotherapy regimens and as parenteral treatment for folate‑deficiency megaloblastic anemia when oral therapy is not feasible.

Site of Care & Product Availability

Note

Injectable formulations available in multiple strengths; appropriate administration settings

Injectable leucovorin is supplied as single‑dose vials in multiple strengths (50, 100, 200, 350, 500 mg); administration may occur in appropriate settings such as infusion centers, hospital outpatient, or office depending on clinical need.

Product availability: single‑dose vials — 50 mg, 100 mg, 200 mg, 350 mg, 500 mg.
Administer IV or IM in settings appropriate for the regimen (e.g., infusion center for IV rescue dosing).

OpenPayer

Leucovorin Injection Coverage Criteria

Coverage Criteria

Initial Therapy

Continuation Criteria

Provider Actions & Requirements

Coding

Definitions

Background

Site of Care & Product Availability