Off-Label Use of Pharmaceuticals and Related Products

Off‐label use is the use of a U.S. Food and Drug Administration (FDA)‐approved therapeutic product in a manner not specifically described in its FDA-approved labeling. This may include use for a different indication, patient population, dosage, route of administration, treatment regimen, or other clinical circumstance.1

The Academy of Managed Care Pharmacy (AMCP) supports off‐label use of U.S. FDA‐approved prescription drugs, biologics, gene therapies, cell therapies, and other FDA-regulated therapeutic products when medically appropriate, safe, necessary, and supported by credible evidence.  

AMCP opposes government‐mandated coverage of specific therapeutic products, whether used for FDA‐approved or off‐label indications, when such mandates can prevent consideration of safe, effective, clinically appropriate, and lower-cost alternatives.  

AMCP believes therapeutic products should be used in accordance with the best available clinical evidence, generally accepted standards of care, and current evidence-based clinical practice guidelines. AMCP also recognizes that pharmacotherapy is a rapidly changing field and that FDA‐approved labeling does 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 when determining whether to provide coverage of an FDA‐approved or otherwise FDA-regulated therapeutic product used off‐label: 

• Evidence of safety and effectiveness. The therapeutic product should be proven safe, effective and accepted for the treatment of the specific medical condition for which it has been prescribed based on nationally recognized drug compendia. Relevant compendia may include the current edition of the 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™.  
• Clinical guidelines and scientific literature. The therapeutic product should be supported by nationally recognized evidence-based guidelines, reproducible formal clinical studies, or credible scientific data published in peer‐reviewed evidence‐based medical literature. 
• Strength and relevance of evidence. Randomized controlled trials generally provide the strongest evidence of clinical effectiveness; however, other forms of high-quality evidence, including real-world evidence, observational studies, pragmatic trials, and registry data, may be appropriate when randomized controlled trials are unavailable, infeasible, insufficient or unethical.  

Coverage decisions should account for advances in specialty pharmacy, precision medicine, biomarker-driven treatment, and individualized patient care when supported by appropriate clinical evidence. Coverage determinations should also consider clinical appropriateness, patient-specific factors, disease severity, potential therapeutic alternatives, and the potential impact of treatment on patient outcomes and quality of life.

AMCP supports timely access to medically appropriate off-label therapies when supported by high-quality evidence and accepted standards of care. Coverage decisions should be transparent, evidence-based, and designed to promote the safe, effective, and affordable use of therapeutic products while preserving flexibility to accommodate advances in clinical practice and emerging scientific evidence.

AMCP opposes coverage mandates that limit the ability of managed care organizations to evaluate clinical evidence, comparative effectiveness, safety, patient needs, and value when designing benefits and making coverage determinations. Benefit design must be the responsibility of managed care organizations so they may ensure the provision of appropriate evidence-based services for their members. AMCP supports the role of clinical pharmacists in evaluating individual coverage determinations based on medical necessity.

Coverage determination, when used in conjunction with other managed care pharmacy tools, such as formularies, drug utilization review, and clinical treatment guidelines, can promote quality and optimal outcomes. As part of developing an evidence-based formulary and utilization management processes, managed care organizations should utilize a variety of tools and strategies with input from practicing health care professionals and independent Pharmacy and Therapeutics (P&T) 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 therapeutic products for off‐label uses. In making these determinations, they should consider high-quality evidence, medical appropriateness, patient-specific circumstances, fiscal responsibility, and principles of compassionate use.

Revised by the AMCP Board of Directors, October 2026

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   

See also:  

• AMCP Legislative and Regulatory Positions 

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.  

²Furey, 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.