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Off-Label Drug Use

Policy Number: MP-184

Latest Review Date: September 2018

Category:  Administrative/Pharmacy                                     

Policy Grade:  N/A

Description of Procedure or Service:

Off-label or “unlabeled” drug use is the use of a drug approved by the U. S. Food and Drug Administration (FDA) for other uses or in treatment regimens or patient populations that are not included in approved labeling.

The FDA approves drugs for specific indications that are included in the drug’s labeling. When a drug is used for an indication other than those specifically included in the labeling, it is referred to as an off-label use. Many off-label uses are effective, well documented in the literature, and widely used.

Unapproved or unlabeled uses of drugs include a variety of situations ranging from completely unstudied to thoroughly investigated drug uses where the FDA has not been asked for approval, whereas approved uses of drugs have been proved to be safe and effective by the FDA after the review of adequate and controlled clinical trials that have documented their uses.



Off-label drug usage may be considered medically necessary for coverage when all of the following conditions are met:

  • The drug is FDA approved.

  • The drug is recognized as appropriate for the stated usage:

  • By one of the following drug compendia: the FDA (listing on the FDA Orphan Drug Approval web site), the American Hospital Formulary Service Drug Information, Thomson Healthcare Inc. DrugPoints, National Comprehensive Cancer Network (NCCN) Drug & Biologics Compendium Category of Evidence and Consensus; OR

  • In the absence of being listed in the above named sources, a minimum of at least two articles from major peer-reviewed journals which supports the proposed use for the specific medical condition as safe and effective.

  • The drug is necessary to treat specific medical conditions, including life-threatening conditions or chronic and seriously debilitating conditions.

Off-label use of a drug does not meet medical criteria for coverage when the FDA has determined its use to be contraindicated.


Key Points:

FDA approved indications, also known as labeled indications, mean that the FDA has reviewed and approved the drug for the specified indications based on adequate, well-controlled clinical trials that have documented safety and effectiveness. The use of a drug for conditions or indication other than those approved by the FDA is known as off-label use.


Key Words:

Off-label use, Food and Drug Administration, FDA


Approved by Governing Bodies:

Not applicable


Benefit Application:

Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if services or supplies are FDA approved and will be reviewed for medical necessity.



CPT codes:                  Not applicable



Not applicable


Policy History:

Medical Policy Group, July 2004 (1)

Medical Policy Administration Committee, July 2004

Available for comment July 29-September 13, 2004

Medical Policy Group, November 2008 (3)

Medical Policy Administration Committee, December 2008

Available for comment November 21, 2008-January 5, 2009

Medical Policy Group, June 2011 (2): Policy revision

Medical Policy Administration Committee, July 2011

Available for comment July 6 through August 22, 2011

Medical Policy Group, July 2011 (2): Revision based on provider comment

Medical Policy Administration Committee, July 2011

Medical Policy Group, January 2014 (1): Policy reviewed by consensus without literature review; no changes in policy statement

Medical Policy Group, January 2015 (3):  Policy reviewed by consensus without literature review; no changes in policy statement

Medical Policy Group, September 2018 (2): Policy reviewed by consensus without literature review; no changes in policy statement.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.