Off-Label Use: Patient Safety Implications

Kim Hathaway, MSN, CPHRM, Patient Safety Healthcare Quality and Risk Management Consultant, and Richard Cahill, JD, Vice President and Associate General Counsel, The Doctors Company

Off-label use of medications and other products has been an accepted practice for many years. For example, Botox was first approved in December 1989 by the U.S. Food and Drug Administration (FDA) to treat blepharospasm and strabismus. In the ensuing years, Botox has been used to treat numerous conditions and was used off-label for 10 years to treat frown lines before gaining FDA approval for cosmetic use.

FDA Off-Label Use

The FDA defines “off-label” use as the unapproved use of an approved medication or product. The approved medication is used for an indication, dosage amount or regimen, patient population, or other use not mentioned in the approved labeling.

Since 1938, the FDA has been empowered by law to review and approve drug products and therapeutic devices for safety and effectiveness. Once approved, a drug product may be prescribed by a licensed physician for any use that is deemed to be appropriate based on the physician’s professional opinion. The standard is what other similarly trained physicians would do—not what the manufacturer of the medication or product recommends. The FDA recognizes that this action by a physician is considered part of the practice of medicine; it does not regulate, comment on, or recommend any course of treatment for an individual.

It is important for advanced practice clinicians (APCs) to review their state practice acts to ensure that prescribing a medication for an off-label use is within their scope of practice. States may expressly permit it, permit it only as part of a supervision or collaboration agreement, or permit it only if certain other requirements are met, such as standard-of-care provisions. While off-label prescribing may not be expressly prohibited, it may be indirectly prohibited if the drug is not included in the APC’s formulary.

Although no rigorous data are available on the extent or profile of off-label uses, off-label practice is often appropriate and may represent standard medical practice. For example, many drugs are not specifically approved for pediatric use, but controls on drug experimentation or product testing in children have resulted in extensive off-label practice. Also, many standard treatments in oncology and HIV therapy involve off-label use of medications.

Obtaining Information on Off-Label Use

Prior to 1997, manufacturers were prohibited from discussing off-label uses with providers, and they could not distribute written materials that mentioned an off-label use or uses. With the Food and Drug Modernization Act of 1997, a manufacturer “may disseminate to a health care practitioner...written information concerning the safety, effectiveness, or benefit of a use not described in the approved labeling of a drug or device if the manufacturer meets...” certain requirements.1 Further FDA clarification on the types of information and the manner of distribution was published in 2009 and revisited again in 2018.2 Manufacturers may also disseminate off-label use information to a pharmacy benefit manager, health insurance issuer, group health plan, or federal and state government agency.

Providers may also obtain information on an off-label use from a pharmaceutical company. Drug companies may not, however, distribute or market off-label use information to patients or the general public. Additionally, the FDA does not restrict other parties from discussing off-label uses or distributing written materials concerning them.

Patient Safety Strategies

Patient safety strategies for clinicians who prescribe a medication or use a medical device in an off-label manner include the following:

  • Ensure that the medication is not an experimental drug. It must have FDA approval for some use and not be for “investigational use.”3
  • Exercise extreme caution when prescribing any drug with a black box warning for an off-label indication. This situation may arise, for example, with antidepressants, anticonvulsants, and antipsychotic drugs used in pediatric and geriatric populations.
  • Study the medication or device, its originally approved use, and the new “off-label” use—including the potential risks and complications, side effects, and contraindications with its use. For example, if the medication literature or package insert states that it is “not for” a particular use, avoid that off-label use.
  • Investigate the acceptance of the proposed off-label use in the medical community or your specialty. Determine whether the proposed off-label use meets the national standards in the specialty or if consensus statements or guidelines for the product exist.
  • Conduct a thorough history and physical to determine whether the patient has any underlying medical conditions that would prohibit the off-label use and whether the patient is taking other medications that might adversely interact with the proposed off-label use.
  • Educate the patient about the medication or product, the proposed off-label use—including the evidence to support the proposed treatment and how you expect the patient to benefit from the medication or device—and the use for which the medication or product received FDA approval.
  • Consider enrolling the patient in a current clinical trial that is studying the off-label use.
  • Consider the costs to the patient, including any substantial out-of-pocket cost for an off-label-product.
  • Obtain the patient’s written consent for off-label use. See our informed consent resources and sample off-label use consent forms for prescription drugs and medical devices.
  • Include these key points in patient education and on written informed consent forms:
    • An off-label use is use of the drug or device in a way that differs from that described on the FDA-approved drug label so all the possible side effects and complications are not known.
    • The use involves a different route, dose, or condition and may change the risk profile of the drug.
    • The details of the treatment have been fully explained and the patient’s understanding was verified.
    • No guarantees about the results of the medication or device were given.
    • The patient is not required to take the medication or use the device.
  • Follow up with the patient on a regular basis to monitor for and document any adverse or unknown reactions to the medication.
  • Contact The Doctors Company at (800) 421-2368 to verify policy coverage of the proposed use of the medication or device prior to implementation.

Off-label use has proved to be very beneficial in the medical community. When approached in a manner consistent with patient safety, it can provide avenues for treatment not otherwise available.


  1. FDA Modernization Act of 1997, 21 U.S.C. § 401, November 21, 1997.
  2. Guidance for industry: good reprint practices for the distribution of medical journal articles and medical or scientific reference publications on unapproved new uses of approved drugs and approved or cleared medical devices. U.S. Food and Drug Administration Website. Updated September 27, 2018.
  3. “Off-label” and investigational use of marketed drugs, biologics, and medical devices—information sheet. U.S. Food and Drug Administration Website. Updated May 6, 2020.


Syed SA, Dixson BA, Constantino E, Regan J. The law and practice of off-label prescribing and physician promotion [published ahead of print November 24, 2020]. J Am Acad Psychiatry Law. 2021 Mar;49(1):53-59.

The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each healthcare provider considering the circumstances of the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

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