Off-Label Use: Patient Safety and Risk Management Implications

Kim Hathaway, MSN, CPHRM, Patient Safety Risk Manager II, 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 Food and Drug Administration (FDA) to treat blepharospasm and strabismus and in December 2000 to treat cervical dystonia. On April 15, 2002, the FDA approved Botox to treat frown lines; however, this has been a widely accepted off-label use for cosmetic purposes for almost 10 years. The FDA defines “off-label use” as the use of a medication or product for an indication, dosage amount or regimen, patient population, or other considered use not mentioned in the approved labeling.1

The FDA is empowered by law to review drug products for safety and effectiveness. FDA approval has been required since 1938, with the additional requirement in 1962 that new drugs be reviewed for both efficacy and safety. It was not until 1976 that the FDA had the authority to regulate medical devices.2

Once approved, a drug product may be prescribed by a licensed physician for any use that, based upon 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. Although the FDA recognizes that this action by a physician is considered to be a part of the practice of medicine, it does not regulate, comment on, or recommend any course of treatment for an individual.

The FDA recognizes that off-label use of drugs by prescribers is often appropriate and may represent the standard of practice. In today’s medicine, many pediatric uses are not on a label. The reason for this off-label practice is the issue of drug or product testing experimentation in children. Many standard treatments in oncology and HIV therapy involve off-label use of medications. There are no rigorous data available on the extent or profile of off-label uses.3

Prior to 1997, manufacturers were prohibited from discussing off-label uses with providers and could not distribute written materials that mention 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.4 Further clarification by the FDA was published in 2009 and revisited again in 2014.5

Physicians may also obtain information on an off-label use from the 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. 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.”6
  • 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, the off-label use should be avoided.
  • Investigate the acceptance of the proposed off-label use in the medical community or specialty in which the physician practices. The physician should also determine if the proposed off-label use meets the national standards in the specialty. For example, direct instillation of antibiotics into the epidural space as a method for prevention and treatment of an infection is a practice without any written information supporting or referencing such treatment.
  • Conduct a thorough history and physical of the patient to determine if there are any underlying medical conditions that would prohibit the off-label use or if there are 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 a sample off-label use form.
  • 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 lay terms or 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 and when approached in a manner consistent with patient safety, can provide avenues of treatment not otherwise available.


  1. Woodcock J. Presented at Drug Information Association Annual Conference, Montreal, June 23, 1997. Used with permission of the U.S. Food and Drug Administration.
  2. HRC Vol. 2, Laws, Regulations and Standards 17, March 1998.
  3. Woodcock J. Presented at Drug Information Association Annual Conference, Montreal, June 23, 1997. Used with permission of the U.S. Food and Drug Administration.
  4. FDA Modernization Act of 1997, 21 U.S.C. § 401, November 21, 1997.
  5. FDA. 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. Published January 2009.
  6. FDA. Off-label and investigational use of marketed drugs, biologics, and medical devices—information sheet guidance for institutional review boards and clinical Published October 17, 2014.

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.

J10007 01/15

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