In clinical practice, physicians may prescribe a medication in a manner that does not align with the guidelines under which it was approved by the U.S. Food and Drug Administration (FDA). This practice, which is prevalent across many medical specialties, is known as off-label drug use (OLDU). Common forms of OLDU include prescriptions of drugs for diseases or symptoms for which they are not FDA-approved, prescriptions to unapproved patient populations, or prescriptions in unapproved dosages or dosage forms. There are advantages and disadvantages to off-label drug use, many of which are not fully understood by both patients and clinicians. [1]

A study based on nationally representative data found that OLDU is common in office-based medicine, accounting for up to 21% of prescription for common medicines. [2] The medications with the most OLDU included albuterol (approved for asthma but used for other obstructive pulmonary indications), gabapentin (an anticonvulsant that is also commonly used for chronic nonspecific pain, anxiety, hot-flashes, and other indications), and aspirin (recommended by some guidelines for coronary disease prophylaxis in diabetic patients, in spite of no FDA approval for this use). [1,2]

The FDA regulates the conduct of clinical research, but it does not regulate clinical practice. Off-label drug use, by itself, is legally permitted if deemed to be medically appropriate for a patient. Furthermore, physicians do not need to disclose to patients if an approved medication is being prescribed for a non-FDA approved indication. [1,5] OLDU offers many advantages: for example, it allows for the treatment of rare (“orphan”) diseases, for which there may not be approved medications due to a lack of drug trials. OLDU in medicine can lead to clinical innovation. [5]

Moreover, OLDU allows for the treatment of populations often excluded from drug trials, such as children, pregnant women, older adults, and people with psychiatric diseases. For example, few selective serotonin reuptake inhibitors (SSRIs, the most common class of antidepressant drugs used in both children and adults) have received FDA approval for use in children, largely due to a paucity of randomized controlled trials in pediatric populations. [4] As a result, OLDU in pediatric psychiatry patients is common. [5] In specialties such as psychiatry, where complex diseases may have overlapping symptoms or features, medications approved for one condition (such as anxiety) may be useful for the treatment of another (such as posttraumatic stress disorder), despite lack of FDA-approval. [1,6] Reauthorization for new usage requires supplemental drug applications that can be costly and time-consuming. [1]

However, off-label drug use can frequently lack sound scientific backing. [2,3] The FDA attempts to control drug use by prohibiting the marketing and promotion of drugs for unapproved uses. Still, many clinicians desire to be educated about the potential uses of drugs, both as approved and for OLDU. Thus, the FDA released guidelines in 2014 to outline recommended practices for drug companies in sharing scientific information on unapproved uses of drugs with clinicians. In October of 2023, the FDA published a new draft of these guidelines, titled “Communications from Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products, Questions and Answers.” While similar to the 2014 guidelines, the update includes additional details and illustrated scenarios on the different ways companies are permitted and prohibited from communicating with health care providers, emphasizing the need for “scientifically sound” and “clinically relevant” information in these communications. Comments on the draft guidelines were accepted until December 26, 2023 and changes will now be finalized.

References

1. Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc. 2012;87(10):982-990. doi:10.1016/j.mayocp.2012.04.017

2. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166(9):1021-1026. doi:10.1001/archinte.166.9.1021

3. Stafford RS. Regulating off-label drug use–rethinking the role of the FDA. N Engl J Med. 2008;358(14):1427-1429. doi:10.1056/NEJMp0802107

4. Dwyer JB, Bloch MH. Antidepressants for Pediatric Patients. Curr Psychiatr. 2019;18(9):26-42F.

5. Rinke ML, Bundy DG, Shore AD, Colantuoni E, Morlock LL, Miller MR. Pediatric antidepressant medication errors in a national error reporting database. J Dev Behav Pediatr. 2010;31(2):129-136. doi:10.1097/DBP.0b013e3181ce6509

6. Alexander W. Pharmacotherapy for Post-traumatic Stress Disorder In Combat Veterans: Focus on Antidepressants and Atypical Antipsychotic Agents. P T. 2012;37(1):32-38.

7. Communications from firms to health care providers regarding scientific information on unapproved uses of approved/cleared medical products questions and answers. Fda.gov. Published 2023. Accessed December 31, 2023. https://www.fda.gov/media/173172/download