compounded products

Compounding and Off-Label Use

Key points:

  1. All products made by every compounding pharmacy in the United States are prescribed “off-label.”
  2. Compounding pharmacies are heavily regulated by FDA and state boards of pharmacy for the quality of their products and safety of their operations.
  3. FDA only controls which medications become available commercially. How doctors choose to prescribe drugs is not regulated by FDA, which means that doctors can freely prescribe drugs “off-label.”

All Compounded Medications Are Prescribed “Off-label”

All products made by compounding pharmacies do not have FDA approval. The FDA approval process is only for manufactured drugs that are commercially available. Since each prescription a compounding pharmacy fills is made for the individual patient, it is exempt from the requirement that a drug go through the FDA approval process. All of the drugs that we use in our preparations are FDA-approved on their own, but when we combine them into a new product they are changed and so they do not fall under the established FDA labeling.

Can Doctors Prescribe Drugs “Off-label”?

FDA approval is a rigorous process that requires clinical trials demonstrating safety and efficacy. An approval is usually a limited indication for a particular drug. For example, the drug naltrexone is FDA approved at a dose of 50mg for the treatment of withdrawal symptoms in opioid addicts. When the drug is made into a capsule that is 4.5mg, it is no longer covered by the established labeling. The clinical trials that demonstrated safety and efficacy were done with 50mg doses, so the FDA does not consider that there is sufficient evidence demonstrating the 4.5mg should be covered by the same approval.

However, almost all healthcare practitioners will prescribe drugs “off-label.” Doctors are not required to prescribe only drugs that are FDA approved, and the FDA does not regulate how they choose to prescribe. In fact, about 20-30% of prescriptions in the United States are for off-label uses. In the case of naltrexone, it was shown years after it was FDA approved that a lower dose could benefit chronic conditions like Crohn’s disease and multiple sclerosis. There would be no financial incentive now for a manufacturer to put low dose naltrexone through the rigorous FDA approval process, which is costly and time-consuming, since the drug is widely available from other sources and the patent has expired. However, healthcare providers find that the 4.5mg dose acts differently than the 50mg dose and helps their patients with chronic conditions. Since the safety of the drug at a higher dose is well established, many practitioners feel confident prescribing the lower dose – even without an FDA indication for chronic diseases.

Compounding Pharmacy Regulation

Although compounded products are exempt from FDA approval if they meet certain standards, compounding pharmacies are still regulated by both the state boards of pharmacy as well as FDA. Our pharmacy has extensive operating procedures and processes for maintaining the quality and safety of our products. We have been through a routine inspection from the FDA and are compliant with all current regulations for compounding pharmacies. The state board of pharmacy is actually the primary regulator for pharmacies of all types including retail pharmacies like CVS as well as compounding pharmacies.

Regulation of what drugs become available commercially FDA
Regulation of how pharmacies operate State Board of Pharmacy, FDA
Regulation of how doctors prescribe State Medical Board

More Information

FDA Position:

FDA has clearly stated its position that it does not regulate prescribing:

“The Food, Drug and Cosmetic Act does not limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment  regimens  or  patient  populations  that  are  not included  in  approved  labeling.  Such  ‘unapproved’ or, more precisely, ‘unlabeled’ uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature.”

ASHP – American Society of Hospital Pharmacists

“The sometimes-used term ‘unapproved use’ is a misnomer, implying that FDA regulates prescribing and dispensing activities. This term should be avoided. Other terminology that is sometimes used to describe unlabeled use includes ‘off-label use,’ ‘out-of-label use,’ and ‘usage outside of labeling.’”