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 authorized medication is used for an indication, dosage amount or regimen, patient population, or other use not specifically mentioned in the approved labeling.

Since 1938, the FDA has been empowered by law to review and approve drug products and therapeutic devices based on safety and effectiveness. Once authorized, a drug product may be prescribed by a licensed healthcare practitioner for any use that is deemed to be appropriate based on the practitioner’s professional opinion. The governing standard is what other similarly trained practitioners would do—not what the manufacturer of the medication or product recommends. Although the FDA recognizes that practitioners may prescribe drugs for an unapproved use when medically appropriate for the patient, it does not regulate, comment on, or recommend any course of treatment for an individual.

One concern about the use of off-label medications is that they are often used on populations that have been historically excluded from clinical research. This group includes, for example, the elderly, mentally ill, pregnant or lactating women, and children.¹ Generally, researchers have refrained from including these populations in clinical research to prevent harm or injury to groups that may be at greater risk of sensitivity to dosing ranges or side effects or who may already have chronic or advanced illnesses that render them frail. Exclusion for ethical reasons has resulted in a paucity of research related to use of drugs in these populations and a knowledge deficit related to therapeutic use of new medications that may benefit vulnerable populations.²

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 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.

For advanced practice clinicians (APCs), it is important to review state practice acts to ensure that prescribing a medication for an off-label use is permitted within their state’s 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.

Obtaining Information on Off-Label Use

Prior to 1997, manufacturers were prohibited from discussing off-label uses with practitioners, 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.³ Further FDA clarification on the types of information and the manner of distribution was published in 2014.⁴ 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.

Practitioners 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 prescribing a medication or medical device for an off-label use 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.”⁵
• 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. Prescribing a medication contrary to a black box warning with a subsequent adverse event may result in a professional liability claim or an investigation by a state licensing board. If an adverse event occurs, practitioners should notify their professional liability insurer for guidance.
• 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. Undertaking due diligence in advance significantly enhances the practitioner’s ability to defend a complaint initiated by a state licensing board or a civil malpractice action seeking monetary damages.
• Conduct a thorough history and physical to determine if the patient has any underlying medical conditions that would prohibit the off-label use or if the patient is taking other medications that might adversely interact with the proposed off-label use. Documenting potential contraindications in the patient record demonstrates the practitioner’s careful thought process. (For more information on documentation, see our article “Defensible Medical and Dental Records.”)
• 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. Implement a standard informed consent protocol that includes a discussion about risks, benefits, and alternative options for treatment. (Find additional guidance on informed consent in our articles “Informed Consent: Substance and Signature” and “Informed Refusal.”)
• Consider enrolling the patient in a current clinical trial that is studying the off-label use of the medication or device.
• Consider the costs to the patient, including any 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 of 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 and contemporaneously noted in the patient record.
• The patient was not given guarantees about the potential results of the medication or device.
• The patient is not required to take the medication or use the device as a condition of continued treatment by the practice or practitioner.
• The patient received written instructions about the types of conditions, signs, or symptoms that could indicate a possible adverse reaction with directions on what to do and who to contact in the event a reaction occurs.
• Follow up with the patient on a regular basis to monitor for and document any adverse or unknown reactions to the medication or device.
• Contact your professional liability insurer to verify policy coverage of the proposed use of the medication or device prior to implementation.

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

For additional assistance, contact the Department of Patient Safety and Risk Management at (800) 421-2368 or by email.

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