Off-Label Use of Pharmaceuticals and Related Products

The Academy of Managed Care Pharmacy (AMCP) supports off‐label use of U.S Food and Drug Administration (FDA)‐approved pharmaceuticals and related products when medically appropriate, safe, and necessary. AMCP opposes government‐mandated coverage of specific pharmaceuticals and related products, whether for FDA‐approved or off‐label uses, that can fail to consider safe, effective, and lower-cost alternatives.  

Off‐label use is defined as the use of a pharmaceutical or related product for clinical indications other than those stated in the product labeling approved by the FDA.¹

AMCP believes each pharmaceutical product on the market should be used only in accordance with credible scientific data and generally accepted standards of medical practices to best ensure safe and effective patient care. AMCP also recognizes that pharmacotherapy is a rapidly changing field and that FDA‐approved uses for particular drug products do not always keep pace with changing clinical guidelines and medical practices.² Therefore, managed care organizations and third-party payers should consider the following criteria before deciding whether to provide coverage of FDA‐approved pharmaceuticals or related products for off‐label uses:

• Whether the pharmaceutical product has been proven safe, effective and accepted for the treatment of the specific medical condition for which it has been prescribed according to nationally recognized drug compendia: the current edition of American Hospital Formulary Service ‐ Drug Information® (AHFS‐DI®), Micromedex® DrugDex®, Clinical Pharmacology, Lexi-Drug®, or the National Comprehensive Cancer Network (NCCN) Drug and Biologics Compendium™. 

• Whether the pharmaceutical product is recommended for the particular condition involved and has been proven to be safe and effective for that condition according to nationally recognized evidence-based guidelines, or reproducible formal clinical studies, or credible scientific data, the results of which have been published in peer‐reviewed evidence‐based medical literature. Randomized, controlled trials are preferred over observational research or case studies. 

AMCP does not believe the government should mandate coverage of specific pharmaceuticals or related products. Benefit design, including coverage determination, must be the responsibility of managed care organizations so they may ensure the provision of appropriate evidence-based services for their members. Coverage determination when used in conjunction with other managed care pharmacy tools, such as formularies, drug utilization review, and medical treatment guidelines, promote quality and optimal outcomes. As part of developing a sound formulary system, managed care plans utilize a variety of tools and strategies with input from practicing health care professionals and Pharmacy and Therapeutic Committees to validate appropriate evidence-based programs and therapies. To ensure the provision of appropriate services for their members, managed care organizations must have authority to determine when to cover pharmaceuticals and related products for off‐label uses, and in making these determinations, should consider high quality evidence, medical appropriateness, fiscal responsibility, and principles of compassionate use.
 
See also: 

• AMCP Legislative and Regulatory Positions

Revised by the AMCP Board of Directors, March 2025 
Revised by the AMCP Board of Directors, December 2020 
Revised by the AMCP Board of Directors, December 2008  
Revised by the AMCP Board of Directors, July 1997  
Adopted by the AMCP Board of Directors, February 1994  

¹Off-Label Use of Prescription Drugs (2021). Congressional Research Service, R45792. Available at https://crsreports.congress.gov/product/pdf/R/R45792/3. See also Understanding Unapproved Use of Approved Drugs "Off Label". Available at: https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label#:~:text=Unapproved%20use%20of%20an%20approved,a%20different%20type%20of%20cancer. 

² Furey, K., Wilkins, K. Prescribing “Off-Label”: What Should a Physician Disclose? (2016). Available at: https://journalofethics.ama-assn.org/article/prescribing-label-what-should-physician-disclose/2016-06