CurrentmhnPolicy CP.PMN.53

Clinical Policy: Off-Label Use

Defines medical necessity criteria, documentation, approval durations, and exclusions for coverage of off-label uses of FDA-approved drugs through pharmacy and medical benefits for Medicaid members affiliated with Centene.

Policy Summary

Payermhn

PolicyClinical Policy: Off-Label Use

Policy CodePolicy CP.PMN.53

Change TypeAnnual reviews / criteria updates

Effective Date09.12.17

Next Review Date

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

SourceLink

POLICY UPDATE CHANGES

Added requirement that alternative drugs be used for at least 30 days and added bypass to all redirections for States with regulations against redirections in certain settings; added depression and transplant to continuity of care programs.

Added requirements if request is for experimental or investigational use with resources to the attestation form per CMS requirements.

Added requirement if a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of the drug-specific clinical policy.

>=30dMinimum alternative trial duration

≤6mInitial approval duration (medical)

≤12mContinued therapy duration

NCCN 1/2A/2B or DrugDex I/IIa

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Accepted evidence levels

Coverage Summary

Scope: Defines medical necessity criteria, documentation, approval durations, and exclusions for coverage of off-label uses of FDA-approved drugs through pharmacy and medical benefits for Medicaid members affiliated with Centene (Policy No. CP.PMN.53).

Coverage stance: Covered with criteria — off-label uses are considered on a case-by-case basis and require prior authorization with supporting documentation.

Subject: Off-Label Drug Use Coverage Criteria.

Policy number: CP.PMN.53.

Effective date: 2017-09-12; Last review date: 2025-11-25.

High-level note: Off-label uses are permitted when the policy criteria are met (e.g., evidence requirements, specialist involvement, failure of alternatives, or clinical trial attestation for routine costs) and when state Medicaid provisions do not conflict with the policy.

Quick-reference thresholds and accepted evidence

Alternative drug trial durationEach alternative tried at maximum indicated doses, each used for at least 30 days or an appropriate duration unless contraindicated or clinically significant adverse effects occur

Approval duration - InitialDuration of request or 6 months (whichever is less) for initial approval (medical benefit specified)

Approval duration - Continued TherapyDuration of request or 12 months (whichever is less)

Accepted evidence levelsNCCN levels 1, 2A, or 2B OR Micromedex DrugDex strength Class I or IIa OR at least two high-quality published studies/guidelines meeting specified criteria

Applied whenUsed only when specific prior authorization criteria do not exist for the diagnosis

I. Initial Approval Criteria - Pharmacy Benefit

Requests for Off-Label Use through Pharmacy Benefit (must meet all):

ALL of the following

There are no pharmacy and therapeutic committee approved off-label use criteria for the diagnosis
If a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of the drug-specific clinical policy
Use is supported by one of the following
- The National Comprehensive Cancer Network (NCCN) Drug Information and Biologics Compendium level of evidence 1, 2A, or 2B
- ALL of the following

I. Initial Approval Criteria - Medical Benefit

Requests for Off-label Use through Medical Benefit (must meet all):

ALL of the following

There are no pharmacy and therapeutic committee approved off-label use criteria for the diagnosis
If a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of the drug-specific clinical policy
Use is supported by one of the following
- The NCCN Drug Information and Biologics Compendium level of evidence 1, 2A, or 2B
- ALL of the following

II. Continued Therapy - Pharmacy or Medical Benefit

Requests for Continued Therapy (must meet all):

ALL of the following

Member meets one of the following
- Currently receiving medication via Centene benefit
- Member has previously met initial approval criteria
- State or health plan continuity of care programs apply to the requested drug and indication with documentation that supports member has received this medication for at least 30 days
  Examples: seizures, heart failure, HIV infection, psychotic disorders (schizophrenia, bipolar disorder), depression, transplant, oncology; refer to state addendums CC.PHARM.03A and CC.PHARM.03B
Use support (one of)

III. Not Authorized Diagnoses/Indications

Diagnoses/Indications for which coverage is NOT authorized:

Indications or diagnoses in which the drug has been shown to be unsafe or ineffective

Policy Identifiers

Policy-level codes/identifiersmixed

CP.PMN.53

Policy Number / Reference Number

Provider Actions & Requirements

Prior Authorization

Prior authorization required for off-label use

Prior authorization is required for off-label use of drugs when coverage is requested under this policy. Providers must obtain authorization before dispensing or administering the off‑label medication to members to ensure the request meets the policy's documented clinical criteria.

Documentation Required

Submit supporting documentation

Submit supporting clinical documentation with the prior authorization request. Acceptable documentation includes office chart notes, laboratory results, imaging, and other records that demonstrate the member meets the policy's evidence and clinical criteria for the requested off‑label indication.

Step Therapy

Background, Evidence & Definitions

Off-label use refers to utilization of an FDA-approved drug for indications, regimens, or populations not included in the approved labeling. The policy evaluates such uses on a case-by-case basis by a physician, pharmacist, or ad hoc committee and provides criteria to determine medical necessity when drug-specific prior authorization criteria do not exist.

The policy aligns with Medicaid requirements by requiring submission of the Medicaid Attestation Form for coverage of routine patient costs associated with qualifying clinical trials and noting that state Medicaid coverage provisions take precedence when they conflict with this policy.

Evidence Source	Accepted Criteria
NCCN Categories of Evidence	Category 1, 2A, or 2B definitions provided in Appendix D (Category 1 = high-level evidence with uniform NCCN consensus; 2A/2B = lower-level evidence with NCCN consensus), accepted as supporting evidence for off-label use
Micromedex DrugDex	Strength of recommendation Class I or IIa accepted (Class I = recommended; Class IIa = generally considered useful; efficacy definitions: Class I = Effective, Class IIa = Evidence Favors Efficacy)

Off-label drug use: Utilization of an FDA-approved drug for uses other than those listed in the FDA-approved labeling or in treatment regimens or populations not included in approved labeling.

Revision History

08.16.22clarified

4Q 2022 annual review; added requirement if a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of the drug-specific clinical policy; clarified drug failure requirements by consolidating multiple requirements and including various scenarios for biosimilars and generics. (P&T Approval Date = 11.22)

07.29.24revised

4Q 2024 annual review updates; added requirement that alternative drugs be used for at least 30 days and added bypass to all redirections for States with regulations against redirections in certain settings (Appendix G); added depression and transplant to continuity of care programs. (P&T Approval Date = 11.24) -- is_material: true

07.10.25

Policy Summary

Payermhn

PolicyClinical Policy: Off-Label Use

Policy CodePolicy CP.PMN.53

Change TypeAnnual reviews / criteria updates

Effective Date09.12.17

Next Review Date

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

SourceLink

On This Page

Adequate representation of the member's clinical characteristics, age, and diagnosis

Adequate representation of the prescribed drug regimen

Clinically meaningful outcomes as a result of the drug therapy in question

Appropriate experimental design and method to address research questions

Micromedex DrugDex with strength of recommendation Class I or IIa

Request is not for a benefit-excluded use (e.g., cosmetic)

If request is for experimental or investigational use, must meet both

Request is for coverage of routine patient costs of qualifying clinical trial services
Provider must submit the completed Medicaid attestation form on the appropriateness of the qualified clinical trial
Form URL: https://www.medicaid.gov/resources-for-states/downloads/medicaid-attest-form.docx

Prescribed by or in consultation with an appropriate specialist for the diagnosis

Failure scenarios (one of)

The preferred biosimilar(s) of the requested brand name drug has been used, if available, unless member has contraindications to the excipients in all generics/biosimilars
Both agents are generics (each from a different manufacturer) within the same therapeutic class as the requested agent
If there is only 1 generic agent within the same therapeutic class, member must use at least one additional agent recognized as standard of care for the diagnosis, provided that such agent exists
If there are no generic agents within the same therapeutic class, member must use 2 alternatives recognized as standards of care for the diagnosis, provided that 2 such agents exist
There are no generic agents within the same therapeutic class and no alternative agents recognized as standards of care for the treatment of the relevant diagnosis

If request is for a non-preferred biologic with available biosimilar, one of

Member must use the preferred biosimilar product(s), unless contraindicated or clinically significant adverse effects are experienced
Request is for a product for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings or for treatment in a State with limitations on step therapy in certain settings (see Appendices E and G)

Member has no contraindications to the prescribed agent per the product information label

If applicable, prescriber has taken necessary measures to minimize any risk associated with a boxed warning in the product information label

Dosing regimen and duration are within dosing guidelines recommended by clinical practice guidelines and/or medical literature

Adequate representation of the member's clinical characteristics, age, and diagnosis

Adequate representation of the prescribed drug regimen

Clinically meaningful outcomes as a result of the drug therapy in question

Appropriate experimental design and method to address research questions

Micromedex DrugDex with strength of recommendation Class I or IIa

Request is not for a benefit-excluded use (e.g., cosmetic)

If request is for experimental or investigational use, must meet both

Request is for coverage of routine patient costs of qualifying clinical trial services
Provider must submit the completed Medicaid attestation form on the appropriateness of the qualified clinical trial
Form URL: https://www.medicaid.gov/resources-for-states/downloads/medicaid-attest-form.docx

Prescribed by or in consultation with an appropriate specialist for the diagnosis

Failure of 2 alternative drugs as described (see pharmacy section) tried at maximum indicated doses, each used for at least 30 days unless contraindicated or clinically significant adverse effects are experienced, or exceptions per state regulationseach used for at least 30 days

If request is for a non-preferred biologic with available biosimilar, one of

Member must use the preferred biosimilar product(s), unless contraindicated or clinically significant adverse effects are experienced
Request is for a product for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings or for treatment in a State with limitations on step therapy in certain settings (see Appendices E and G)

Member has no contraindications to the prescribed agent per the product information label

If applicable, prescriber has taken necessary measures to minimize any risk associated with a boxed warning in the product information label

Dosing regimen and duration are within dosing guidelines recommended by clinical practice guidelines and/or medical literature

NCCN Drug Information and Biologics Compendium level of evidence 1, 2A, or 2B
ALL of the following
- Adequate representation of the member's clinical characteristics, age, and diagnosis
- Adequate representation of the prescribed drug regimen
- Clinically meaningful outcomes as a result of the drug therapy in question
- Appropriate experimental design and method to address research questions
Micromedex DrugDex with strength of recommendation Class I or IIa

Member is responding positively to therapy

If request is for a non-preferred biologic with available biosimilar, one of

Member must use the preferred biosimilar product(s), unless contraindicated or clinically significant adverse effects are experienced
Request is for a product for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings or for treatment in a State with limitations on step therapy in certain settings (see Appendices E and G)

If request is for a dose increase (quantity or frequency), member has been titrated up from the lower dose with documentation of partial improvement, and the new dose does not exceed dosing guidelines recommended by the product information label or clinical practice guidelines and/or medical literature

Step therapy / therapeutic alternatives required

Step therapy or therapeutic alternatives are required when applicable. Providers must document trials and failures (or contraindications) of required alternatives per the policy (typically two alternatives tried at appropriate doses and durations, or use of preferred biosimilars when available) before approval of the requested off‑label agent.

Documentation Required

Specialist prescription/consultation

Prescriptions for off-label uses should be written by, or include consultation from, an appropriate specialist for the diagnosis. Include the specialist's documentation or consultation notes with the request to support medical necessity.

Denial Risk

Excluded uses denied

Requests for uses that are benefit‑excluded (for example, cosmetic indications) will be denied. Providers should confirm the requested indication is not explicitly excluded by the plan before submitting a request.

Billing Rule

Continuity of care documentation

For continuity of care situations, submit documentation demonstrating the member has been receiving the medication (e.g., at least 30 days) along with any state- or plan‑specific continuity provisions. This may impact approval and duration decisions.

4Q 2025 annual review; added requirements if request is for experimental or investigational use with resources to the attestation form per CMS requirements. (P&T Approval Date = 11.25) -- is_material: true