Off-Label Drug Use: Minimizing the Risks

According to the U.S. Food and Drug Administration (FDA), off-label use is the prescribing of an approved drug for an unapproved use, or use of a drug outside of the package insert and label information. Off-label drug use can include use for an indication other than the one approved, in an unapproved dosage form or route of administration, or in a dosage or duration of therapy that varies from the label information. It is also considered off-label to use a drug in an unapproved patient population. 

While the FDA regulates the premarket approval of all new drugs, it does not limit or control how approved medications are prescribed. Due to the rapidly changing healthcare environment and vigorous research climate, there may be strong scientific evidence to use a drug off-label. In some situations, off-label use may be the standard of care, and withholding the drug may be a disservice to the patient. For example, off-label drugs are commonly used in oncology where data suggests that a drug approved for one type of cancer works well against several other types of cancers. 

Off-label prescribing is relatively common—about 30% of all prescriptions are written off-label. However, the prevalence of off-label drug use is much higher in populations such as pediatric and elderly patients, pregnant patients, and patients with mental health disorders. Because these groups are commonly excluded from clinical drug trials for ethical, safety, and legal reasons, there is a lack of drug efficacy and safety data for those populations. Recent studies have shown that up to 80% of pregnant patients and 97% of hospitalized pediatric patients are prescribed drugs off-label.

Risk Recommendations: 

Off-label prescribing is often in the patient’s best interest, but it can expose the patient to safety risks and the practitioner to liability. Practitioner education, effective communication, shared decision–making, and well-designed policies and procedures can minimize the risk associated with off-label prescribing. Consider the following risk management strategies when evaluating the prescribing practices at your organization: 

• Provide written guidance. Develop a policy and procedure for off-label prescribing that addresses key elements, including:
  • A process to determine the appropriateness of off-label use that is prompted by strong scientific evidence, supported by standard treatment guidelines, or designated as a “medically accepted indication” by nationally recognized, authoritative drug compendia.
  • A set of guidelines for ethics, pharmacy and therapeutics, or quality committees to review when determining the appropriateness of off-label use.
  • A medication reconciliation process.
  • A set of requirements for obtaining written informed consent for off-label use.
  • A mechanism to track and report adverse drug events (ADEs) associated with off-label use.
• Know the medications you prescribe. Off-label prescribing may be associated with a lack of knowledge of approved treatment indications. In these instances, there is a high risk for off-label use without strong scientific evidence, and hence an increased risk for liability. Encourage practitioners to understand and acknowledge the importance of knowing the package insert and label information for all medications prior to prescribing them.
• Ensure that off-label use is evidence-based. Off-label use without strong scientific evidence is associated with higher rates of adverse drug events (ADEs). Ensure that strong scientific evidence exists prior to prescribing an off-label medication. Never assume that a medication is safe for a pediatric patient simply because it has been established as safe and efficacious in the adult population.
• Understand reimbursement issues. Confirm reimbursement prior to prescribing an off-label drug to avoid surprises at the pharmacy counter. While many payers recognize the benefits of off-label use, some decline or limit coverage in certain circumstances. For example, Centers for Medicare & Medicaid Services (CMS) will reimburse for off-label anti-cancer chemotherapy regimens if there is a “medically accepted indication” listed in one of five nationally recognized, authoritative compendia. 
• Educate the patient and obtain consent. Utilize plain language principles to discuss with the patient the reasons for prescribing medication off-label, the benefits of prescribing it, the risks associated with it, and the alternatives to using it. Obtain the patient’s written informed consent and document the consent discussion in the medical record. As with all medications, ensure that the patient understands how to recognize, report, and manage potential side effects and expected treatment response.
• Recognize and report improper drug promotion. While the FDA requires prescription drug advertising and promotion to be truthful, balanced, and accurately communicated, the agency continues to receive reports of improper drug promotion. Scrutinize information provided by pharmaceutical manufacturers to ensure your prescribing practices are based on sound medical evidence. Know how to recognize and report suspected false or misleading drug advertising or promotion. 
• Document. Support your decision to prescribe medications off-label with thorough documentation in the medical record. Include your rationale for prescribing the medication and any discussions you have with the patient about the medication, including the risks, benefits, and alternatives to using the medication. Document the patient’s response to the medication, including any adverse events.
• Report adverse events. Report all medication-related adverse events through your organization’s incident reporting system and the FDA’s MedWatch reporting system. 

Off-label medication use gives the patient additional treatment options, but it can also expose the patient to risk and the prescriber to liability. Safe prescribing practices help minimize risk.