Off-Label Use vs. Not FDA-Approved: Critical Distinction
No, off-label use is NOT the same as not FDA-approved—off-label refers to using an FDA-approved drug for an indication, dosage, or population that was not included in the approved labeling, whereas not FDA-approved means the drug itself has never received FDA approval for any indication. 1, 2
Key Definitional Differences
Off-Label Use
- The drug itself IS FDA-approved, but is being prescribed for conditions, populations, or dosing regimens not included in the FDA-approved labeling 1, 2
- This is a legal and common practice in medicine—the FDA does not regulate the practice of medicine, only drug marketing 3
- Examples include using isotretinoin (FDA-approved only for severe recalcitrant nodular acne) for moderate acne that is treatment-resistant 2
Not FDA-Approved
- The drug has never received FDA approval for any indication 4
- These are typically compounded medications, investigational drugs, or products marketed without going through the FDA approval process 4
- Providers should be knowledgeable about unapproved products and consider switching patients to FDA-approved alternatives when possible 4
Clinical Implications
For Off-Label Use
- Prescribing is legal and often appropriate when standard FDA-approved therapies have failed or for treatment-resistant conditions causing physical or psychological distress 5
- In oncology specifically, off-label use increased from one-third of cancer drugs in 1991 to between one-half and three-quarters by 2005 5, 4
- Medicare covers all oncology drugs listed in approved compendia for off-label uses, making this practice more accessible 5, 4
For Not FDA-Approved Products
- Higher quality and safety risks exist because these products have not undergone FDA review for safety, efficacy, or manufacturing standards 4
- Clinicians should understand that some injectable products may have been prepared by compounding pharmacies with associated quality risks 4
Regulatory Framework Distinctions
Off-Label Prescribing
- Pharmaceutical companies cannot market or promote off-label uses—this has led to several large settlements for illegal marketing 3
- Federal regulations mandate that all Risk Evaluation and Mitigation Strategies (REMS) must be consistent with approved labeling, preventing manufacturers from providing risk information for off-label uses 4
- The CDC can provide guidelines for off-label uses that differ from FDA-approved labeling, as demonstrated with bedaquiline for multidrug-resistant tuberculosis 1
Not FDA-Approved Products
- These products lack any FDA oversight for marketing 4
- No approved labeling exists to guide safe use 4
Prescriber Responsibilities
When Considering Off-Label Use
- Document thorough informed consent discussing: the off-label nature of the prescription, alternative treatment options, specific risks and benefits, and monitoring requirements 2
- Base decisions on understanding of risks and benefits, using FDA labeling, medical literature, published guidelines, drug compendia, and continuing education 5
- Establish baseline and ongoing monitoring based on the medication's known adverse effect profile 5
- Prescribe only for indications believed to be in the best interest of the patient to limit liability 3
When Encountering Not FDA-Approved Products
- Actively consider switching to FDA-approved alternatives when selecting drug therapy 4
- Understand the elevated quality and safety risks associated with unapproved products 4
Common Pitfalls to Avoid
- Do not confuse appropriate off-label use with inappropriate off-label use—appropriate off-label use has demonstrated efficacy through evidence and expert judgment, while inappropriate off-label use lacks proven benefits and unnecessarily exposes patients to toxicity 1
- Do not assume insurance coverage—while Medicare covers off-label oncology uses listed in compendia, most commercial insurers restrict coverage to FDA-approved indications only 4
- Do not overlook special populations—off-label use in pediatric, pregnant, or elderly patients requires additional caution as safety profiles may differ from adults 5, 6