Methotrexate (Otrexup, Rasuvo, Xatmep, Reditrex, Jylamvo) coverage
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Defines medical necessity and prior authorization criteria for injectable and oral solution methotrexate products (Otrexup, Rasuvo, Xatmep, Reditrex, Jylamvo) across Health Net lines of business; applies to providers requesting coverage for these products.
No material clinical or coverage changes in this revision.
Coverage Criteria
Initial Therapy — Initial Approval Criteria — Methotrexate products are medically necessary when ALL of the following are met as specified per indication
Initial Approval Criteria — Methotrexate products are medically necessary when ALL of the following are met as specified per indication
General requirements
- Covered products/indications: Includes pJIA, RA, PsO, ALL, MF, relapsed/refractory NHL as listed
Refer to indication-specific nodes
- Prescriber specialty: Prescribed by or in consultation with the appropriate specialist (rheumatologist for RA/pJIA; dermatologist for PsO; oncologist/hematologist for ALL, MF, NHL)
pJIA (polyarticular juvenile idiopathic arthritis)
pJIA-specific initial criteria (must meet ALL):
See product labeling for exact dosing regimens
Rheumatoid arthritis (RA) or Psoriasis (PsO)
RA or PsO initial criteria (must meet ALL):
Approval durations vary by line of business per policy
Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia (ALL) initial criteria (must meet ALL):
Prescriber must submit supporting evidence for any off-label dosing
Mycosis Fungoides and Non-Hodgkin Lymphoma
Mycosis Fungoides (MF) and Non-Hodgkin Lymphoma (NHL) initial criteria (must meet ALL):
Prescribed regimen must be FDA‑approved or recommended by NCCN; prescriber must submit supporting evidence for off-label dosing
Prescribed regimen must be FDA‑approved or recommended by NCCN
General Coverage — Coverage is subject to formulary status and labeled indications; off‑label uses require documentation per off‑label policies.
Coverage is subject to formulary status and labeled indications; off‑label uses require documentation per off‑label policies.
See CP.CPA.190, HIMPA.33, CP PMN.255 and off‑label policies (e.g., CP.PMN.53) for details
Product Label Dosing Constraints
Dosing and indication constraints for coverage follow product labeling:
Exact doses and maxima per product labeling; prescriber should reference Dosage and Administration for specifics
Otrexup, Rasuvo, and Reditrex are not indicated for the treatment of neoplastic diseases. This limitation of use is specified in the product labeling and reiterated in the policy’s general information appendix.
Otrexup, Rasuvo, and Reditrex are not indicated for the treatment of neoplastic diseases. In addition, these products carry contraindications and boxed warnings that affect coverage and safe use: pregnancy is listed as a contraindication, and other contraindications include alcoholism or liver disease, immunodeficiency syndromes, pre‑existing blood dyscrasias, and severe hypersensitivity to methotrexate. The labeling also includes a boxed warning for severe toxic reactions, including embryo‑fetal toxicity and death.
Requests for non‑FDA approved (off‑label) indications that are not addressed in this policy will be considered not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (commercial: CP.CPA.09; HIM: HIM.PA.154; Medicaid: CP.PMN.53) or other evidence of coverage documents.
Initial Therapy (Drug-Specific)
Initial therapy (drug-specific) — Initial therapy criteria organized by indication and product
Initial therapy criteria organized by indication and product
Refer to Dosage and Administration and product labeling
Refer to Dosage and Administration and product labeling
Prescribed regimen must be FDA‑approved or recommended by NCCN
Prescribed regimen must be FDA‑approved or recommended by NCCN
Initial Therapy / Label Conformance — Initial dosing must align with labeled regimens per product and indication.
Initial dosing must align with labeled regimens per product and indication.
Requests for injectables for neoplastic treatment should only be made when the product is indicated
Continuation Therapy
Continuation Therapy — Continued therapy criteria (must meet one of the following)
Continued therapy criteria (must meet one of the following):
Dose increase requests must not exceed indication-specific dose limits unless supported by practice guidelines or peer-reviewed literature
Continuation therapy durations — Continuation/renewal requirements and duration limits
Continuation/renewal requirements and duration limits
See policy approval duration section for specific indication exceptions
Approval Durations / Continuation — Approval durations for continuation/renewal vary by line of business and product.
Approval durations for continuation/renewal vary by line of business and product.
Refer to the Approval Duration section for indication-specific variations
Coding & Dose Limits
Step Therapy Requirements
| Step | Requirement | Applies to |
|---|---|---|
| 1 | Failure of generic methotrexate injection unless contraindicated or clinically significant adverse effects are experienced | Otrexup, Rasuvo, Reditrex (branded injectable methotrexate) |
| Reference | When to consult | Notes |
|---|---|---|
| CP.CPA.190; HIMPA.33; CP PMN.255 (line-of-business formulary/no‑coverage policies) | When the requested product is subject to step therapy, non‑formulary, or no‑coverage rules, or when recent label changes are not reflected in this policy | Follow the referenced line‑of‑business policy for formulary, non‑formulary, and off‑label determinations; see corresponding marketplace/Medicaid variants as applicable |
Provider Actions & Requirements
Documentation Required
Prior authorization is required for these products. Provider must submit supporting documentation (office chart notes, lab results, imaging, or other clinical information) demonstrating the member meets all applicable approval criteria. Failure to submit sufficient documentation may result in denial or delay of the request.
- Submit relevant clinic notes including diagnosis, prior therapies/trials, and rationale for the requested agent.
- Include laboratory data and any documentation of contraindications or adverse reactions to prior methotrexate formulations.
- If request is for a non‑FDA or off‑label indication, include evidence of efficacy and safety per the applicable off‑label use policy.
Formulary / Off‑label Documentation
If the requested drug is on or off the formulary, or a recent label change has occurred (within the last 6 months), providers must follow the referenced formulary/non‑formulary and off‑label policies for the applicable line of business. Requests for non‑formulary drugs should be routed per the relevant non‑formulary policy.
- Commercial formulary/non‑coverage: CP.CPA.190
- Health insurance marketplace formulary/non‑coverage: HIMPA.33 or HIM.PA.103 (as applicable)
- Medicaid formulary/PDL/non‑coverage: CP.PMN.255 or CP.PMN.16 (as applicable)
- Off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid)
Step: Generic Injectable Failure Required
Step therapy applies when the policy requires failure of generic methotrexate injection prior to approving certain branded autoinjector products. For Otrexup, Rasuvo, and Reditrex, the request must document prior trial and inadequate response, contraindication, or clinically significant adverse effect to generic methotrexate injection unless an exception is provided.
- Document the product name(s), dose, duration, and reason for discontinuation of prior generic injectable methotrexate.
- If a generic injectable trial is contraindicated or caused significant adverse effects, include supporting clinical documentation.
Formulary / Step Considerations
Formulary and step‑therapy considerations may affect coverage and prior authorization decisions. Refer to the applicable no‑coverage, non‑formulary, or off‑label policies when step therapy or formulary hierarchy impacts access. If the requested use or patient age/dosing is outside this policy's stated indications, follow the off‑label and formulary rules for the member's line of business.
- When a recent label change is not yet reflected in this policy, consult the listed formularies and off‑label policies.
- Coverage for non‑FDA indications may be denied unless sufficient documentation per the off‑label policy is provided.
Definitions
Quantity Limits & Product-Specific Maximums
Site of Care
Site of care determined by formulation and route
Products include auto‑injector formulations (Otrexup, Rasuvo, Reditrex) and oral solutions (Xatmep, Jylamvo); site of care is determined by route — oral solution is administered at home, and auto‑injector use may be at home or clinic per prescriber instruction.
- Oral solutions: Xatmep (2.5 mg/mL), Jylamvo (2 mg/mL)
- Auto‑injectors/single‑dose prefilled injections available in multiple strengths for injectables
Background
Methotrexate is a folate metabolic inhibitor used across autoimmune and selected oncologic indications. Formulations covered include subcutaneous injectable auto‑injectors (Otrexup, Rasuvo, Reditrex, Jylamvo) and an oral solution (Xatmep). Clinically, methotrexate is used for autoimmune conditions such as rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (pJIA), and psoriasis (PsO), and certain formulations or regimens are used as part of oncology treatment plans (for example, acute lymphoblastic leukemia [ALL], mycosis fungoides [MF], and relapsed/refractory non‑Hodgkin lymphoma [NHL]) where the specific product labeling and indication permit. Note that Otrexup, Rasuvo, and Reditrex are explicitly not indicated for neoplastic diseases per labeling.
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