CurrentCapital BluecrossPolicy MP 2.103

Off‑Label Use of Medications and Other Interventions

Defines when off-label use of FDA‑approved drugs, biologics, devices, or other interventions may be considered medically necessary and the evidence sources Capital BlueCross will accept; applies to members and providers covered by applicable Capital Blue Cross programs.

Policy Summary

PayerCapital Bluecross

PolicyOff‑Label Use of Medications and Other Interventions

Policy CodePolicy MP 2.103

Change TypeRoutine review — no material changes

Effective DateOct 1, 2025

Next Review Date

Key ActionProvider must document the product is FDA-approved and supply supporting evidence from accepted sources to justify off‑label use.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

All uses require FDA approvalFDA approval required

Multiple accepted sourcesAccepted evidence sources

See MP 2.373Stage IV cancer guidance

InvestigationalNon‑FDA products

Medicare/FEP noted

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Off‑Label Use Coverage Criteria

Off‑Label Use — Medical Necessity Criteria

Off‑label use may be considered medically necessary when ALL of the following are met:

All criteria: The drug, biologic, or device is approved by the United States Food and Drug Administration (FDA).

All criteria: There are no specific contraindications to the proposed use for the specific member.

If the FDA or the evidence sources listed in this policy determine the use is contraindicated or not indicated/not recommended for specific conditions or patient groups, that use is considered investigational and excluded from coverage.

If the FDA has determined a drug, biologic, or device to be contraindicated for a proposed use, that use is excluded from coverage and is considered investigational. The policy also treats uses as investigational when the evidence sources listed in this policy (e.g., accepted standards of practice, national specialty society guidelines, peer‑reviewed literature, DrugDex/AHFS, NCCN, Clinical Pharmacology, Lexi‑Drugs rated Use: Off‑Label Evidence Level A, ICER, or Blue Cross Blue Shield Association Evidence Street) deem the use to be not indicated or not recommended for specific conditions or defined patient groups.

Products that have not received FDA approval for any indication are considered investigational for all uses and are excluded from coverage under this policy.

Off‑label uses that lack support from at least one of the policy’s accepted evidence sources — or that are specifically contraindicated by the FDA or by the listed compendia/guidance sources — are considered not medically necessary/investigational and will not be covered.

Procedure and Code Guidance

Procedure Codingmixed

No codes listed

Procedure coding applicability

ApplicabilitySpecific procedure coding does not apply to this policy.

Coding noteCode lists provided in coding sections do not denote coverage; coverage determined by member benefit terms.

UpdatesCodes are subject to change and may not be all‑inclusive; verify current code sets before billing.

Provider Requirements and Authorization

Denial Risk

Investigational or Contraindicated Uses

Investigational or contraindicated uses: Requests for uses that the FDA has determined to be contraindicated, or uses that the compendia/sources listed in this policy deem not indicated or not recommended for specific conditions or defined patient groups, will be considered investigational and are not medically necessary.

Includes any request for a drug, biologic, or device that has not received FDA approval for any indication
Includes off-label uses specifically contraindicated by the FDA or judged not indicated by the authoritative sources referenced in this policy

Documentation Required

Required Supporting Documentation

Required supporting documentation: Provider must document FDA approval status and supply supporting evidence from accepted sources to justify off-label use.

Documentation of the FDA-approved indication(s) and statement of the proposed off-label indication

Background

FDA approvals are indication‑specific; using a drug, biologic, or device outside its labeled indications is considered off‑label use. While many off‑label uses may be supported by evidence, this policy requires the product to be FDA‑approved and the proposed off‑label use to be supported by at least one accepted evidence source (for example, accepted standards of medical practice, expert opinion identified by Capital, national specialty society practice guidelines, peer‑reviewed articles, DrugDex/AHFS, NCCN, Clinical Pharmacology, Lexi‑Drugs rated Evidence Level A, ICER, or Evidence Street) and to have no specific contraindications for the member in order to be considered medically necessary.

Key Definitions and Compendia

COMPENDIA

DefinitionCOMPENDIA: A comprehensive listing of FDA‑approved drugs and biologicals or a comprehensive listing of a specific subset of drugs and biologicals in a specialty compendium.

Content requirementsIncludes a summary of pharmacologic characteristics, may include dosage and recommended or endorsed uses in specific diseases.

Evaluation processMust have a publicly transparent process for evaluating therapies and for identifying potential conflicts of interest.

ExamplesMay include specialty compendia such as an anti‑cancer treatment compendium with indexed drug/biologic entries.

OFF-LABEL USE

DefinitionOFF‑LABEL USE: The use of a prescription drug or medical device in the treatment of an illness or injury, which can include different dosing, for which it has not been specifically approved by the FDA.