What does it mean to use a medication off-label?

Understanding Off-Label Medication Use

Off-label medication use refers to prescribing FDA-approved drugs for indications, patient populations, dosages, or routes of administration that are not included in the FDA-approved product information or labeling. 1, 2

What Constitutes Off-Label Use

Off-label prescribing includes:

• Using medications for unapproved indications
• Using a drug outside recommended dosage ranges or duration
• Prescribing for unapproved patient populations (defined by age, sex, or clinical parameters)
• Using a medication in patients with known contraindications 2

Prevalence and Scope

Off-label prescribing is extremely common in clinical practice:

• Up to 40% of prescriptions in adult medicine
• Up to 90% of prescriptions in pediatric medicine 3
• Particularly prevalent in oncology, where between one-half and three-quarters of cancer drugs are used off-label 1
• More common in populations less likely to be included in clinical trials (pediatric, pregnant, or psychiatric patients) 4

Legal Status and Regulation

• Off-label prescribing is not illegal and is considered part of the practice of medicine 2, 4
• The FDA regulates drug approval but does not regulate the practice of medicine
• Pharmaceutical companies are prohibited from promoting drugs for off-label uses, with significant legal penalties for violations 4
• Federal regulations mandate that Risk Evaluation and Mitigation Strategies (REMS) components must be consistent with the drug's approved labeling, creating challenges for appropriate off-label use 1

Appropriateness of Off-Label Prescribing

Off-label use can be considered appropriate in three main categories:

1. Evidence-justified use: Supported by high-quality scientific evidence
2. Research context use: Within formal research proposals or clinical trials
3. Exceptional use: Justified by individual clinical circumstances when standard treatments have failed 3

Best Practices for Off-Label Prescribing

When considering off-label use, physicians should:

• Evaluate available scientific evidence supporting the proposed use
• Assess the patient's treatment history and response to approved therapies
• Weigh potential risks and benefits based on clinical pharmacology and available studies
• Obtain appropriate informed consent from patients regarding the off-label nature of treatment
• Document the rationale for off-label use in the medical record 2, 5

Informed Consent Considerations

Patients should be informed about:

• The off-label status of the medication
• Why this approach is being recommended
• The evidence (or lack thereof) supporting this use
• Known risks, benefits, and side effects
• Alternative treatment options 2

Common Pitfalls and Challenges

• Prescribing without adequate scientific evidence supporting safety and efficacy
• Failing to obtain proper informed consent regarding off-label status
• Not documenting rationale for off-label use
• Exposing patients to unnecessary risks when evidence is lacking
• Administrative barriers in healthcare systems that may complicate off-label prescribing 5, 6

Improving Off-Label Prescribing Practices

The medical community can enhance appropriate off-label use by:

• Promoting evidence gathering when data is inadequate
• Developing institutional guidelines for common off-label uses
• Encouraging professional societies to evaluate and provide guidance on off-label uses
• Supporting research to generate evidence for commonly used off-label indications 5

Understanding off-label medication use is essential for healthcare providers to make informed decisions that balance providing innovative treatment options with ensuring patient safety and informed consent.