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

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.

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.

The FDA is empowered by law to review drug products and therapeutic devices for safety and effectiveness. FDA approval for safety has been required since 1938. An amendment in 1962 required drug manufacturers to demonstrate the efficacy of their products before marketing them.

Once approved, a drug product may be prescribed by a licensed physician for any use that, based on the physician’s professional opinion, is deemed to be appropriate. The standard is what other similarly trained physicians would do—not what the manufacturer of the medication or product recommends. Since 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.

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.

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 clarification by the FDA was published in 2009 and revisited again in 2018.2

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

The patient safety implications for physicians in prescribing a medication or using 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
  • Become knowledgeable about 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.
  • 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, and the use for which the medication or product received FDA approval.
  • Obtain the patient’s written consent for off-label use. Visit our Informed Consent resource center for sample off-label use consent forms: prescription drugs and medical devices.
  • Note that the key points in patient education and consent include the following:
    • A statement that the off-label use is an “experimental use,” so all the possible side effects and complications are not known.
    • A list of the common and/or known risks and complications with use of the medication.
    • A statement that the details of the treatment have been fully explained in terms that are easily understood by the patient.
    • A statement that no guarantees about the results of the medication are given.
    • A statement that the patient is not required to take the medication.
  • Contact the Underwriting Department of The Doctors Company to verify coverage of the proposed use of the medication prior to the planned use.
  • Follow up with the patient on a regular basis to monitor for any adverse or unknown reactions to the medication.

Off-label use has proven 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 July 13, 2018.

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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