BlueCross and BlueShield of Montana Medical Policy/Codes
Off-Label Use of U.S. FDA Approved Drugs
Chapter: Drugs - Medical Benefit
Current Effective Date: December 27, 2013
Original Effective Date: January 01, 2001
Publish Date: December 27, 2013
Revised Dates: April 11, 2007; May 9, 2008; September 4, 2009; December 12, 2013

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 shown to be safe and effective by the FDA after the review of adequate and controlled clinical trials that have documented their uses.


A compendium is a comprehensive listing of FDA-approved drugs and biologics. In some cases, compendia specialize in a particular subset of drugs, such as those used for anti-cancer treatment. Compendia include a summary of how each drug works in the body, as well as information for health care practitioners about proper dosing and whether the drug is recommended or endorsed for use in treating a specific disease. A compendium may be used as one of several tools to determine whether a drug should be covered.


Each benefit plan or contract defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers have the responsibility for consulting the member's benefit plan or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan or contract, the benefit plan or contract will govern.


Off-Label use of U.S. Food and Drug Administration (FDA) approved drugs as prescribed by a physician to treat chronic, disabling, or life-threatening illnesses may be considered medically necessary when meeting the criteria outlined below:

  • Has been approved by the FDA for at least one indication, AND
  • Is in one of the following standard reference compendia for the off-label indication:
  1. Thompson Micromedex DrugDex Compendium (DrugDex);
  2. American Hospital Formulary Service Drug Information (AHFS DI);
  3. National Comprehensive Cancer Network's Drugs and Biologics Compendium;


  • Is supported by clinical research that appears in peer-reviewed literature specific for the indication in question.

NOTE:  Peer-reviewed scientific literature means published scientific studies that have been critically reviewed by unbiased independent experts in the same field for scientific accuracy, validity, and reliability.  Medical policy coverage positions are most strongly influenced by results of large, multi-centered, prospective, randomized, and double-blinded trials in the peer-reviewed scientific literature. Least credence is given to studies or publications with significant sponsorship by pharmaceutical companies or other financially interested entities.

Coverage of a drug that meets the coverage criteria shall also include medically necessary services associated with the administration of the drug.

Off-Label use of FDA approved drugs is considered non-covered when the FDA has determined its use to be contraindicated for treatment of the condition for which coverage is requested.

NOTE:  If there is an HCSC medical policy regarding a specific drug, such medical policy supersedes use of this Off-Label Use policy.

Orphan Drugs

Use of an orphan drug may be considered medically necessary when used to treat rare diseases and disorders as defined by the Orphan Drug Act of the U.S. Food and Drug Administration.

An Orphan Drug is defined in the 1984 amendments of the Orphan Drug Act as "a drug intended to treat a condition affecting fewer than 200,000 persons in the United States or will not recover development cost, plus a reasonable profit, within seven years following FDA approval. The Orphan Drug Act was signed into law on January 4, 1983."


This medical policy was undated with literature review through May 2012.  Rationale revised.  In certain instances scientific evidence may support using a drug to treat a disease even if the drugs FDA approved label does not include those clinical conditions.  In these circumstances the compendia or scientific peer-reviewed literature specific for the indication in question may recommend uses beyond those included in the FDA approved labels.  Medical policies on specific drugs are reviewed for consideration of change when valid new scientific literature emerges.


Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

  1. Legislature of the State of Texas. Section 1.  Subchapter E, Chapter 21, Insurance Code.  Article 21.53H Coverage for Off-Label Uses of FDA Approved Drugs.
  2. Illinois Mandated Benefits; Cancer Off-Label Drugs 215 ILCS 5/370 or, 215 ILCS 125/4-6.3.
  3. New Mexico Mandated Benefits, Prescription Drugs 13:10. 13:12
  4. Oklahoma Statutes Citationized Title 63. Public Health and Safety Chapter 1 - Oklahoma Public Health Code Article 26 - Kidney Health Planning Act of Oklahoma Section 1-2604 - Coverage for Prescription Drugs for Cancer Treatment or Study of Oncology.
  5. AMA House of delegates Health and Ethics Policies, H-120.988 Patient Access to Treatments Prescribed by Their Physicians.
  6. Dresser, R., At Law:  The Curious case of Off-Label Use.  The Hastings Center Report.  6/7/2007.
  7. Off-Label Drug Use. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2011 December) Prescription Drug: 5.01.01.
December 2013  Policy formatting and language revised.  Title changed from "Off-Label Drug Use Including Chemotherapy and Biologic Drugs" to "Off-Label Use of U.S. Food and Drug Administration (FDA) Approved Drugs".
®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.
CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
Off-Label Use of U.S. FDA Approved Drugs