Compounded Medications: Reviewing Safety and Effectiveness

Compounded medications have traditionally served as therapeutic alternatives for patients with unique medical needs that cannot be met by available FDA-approved medications. Compounding is a long-standing pharmaceutical practice that allows critical medical treatments to be produced on a patient-specific and as-needed basis. Given its historic rationale, compounded medications are not subject to the same level of extensive testing and stringent regulatory oversight as FDA-approved medications.

In recent decades, however, the practice of compounding has greatly expanded and millions of Americans report using compounded medications every year. This increased interest is due in part to marketing claims of safety and effectiveness, as well as a growing interest in personalized medicine. However, these medications are not FDA approved and there is little data to support the safety or effectiveness of each uniquely prepared formulations.

Until better research data can be gathered to inform practitioners and patients on the benefits and potential risks, compounded medications should only be prescribed and used in limited circumstances. Two recent reports from the National Academies of Sciences, Engineering, and Medicine explain what compounding is and why the widespread use of two particular types of compounded medications—compounded topical pain cream and compounded bioidentical hormone therapy—is a public health concern.

What is Compounding?

Compounding is the process of combining, mixing, or altering ingredients to create a medication tailored to the medical needs of a patient. This process can either start by altering an FDA-approved drug, or by creating an entirely new formulation.

Compounded medications can provide therapeutic alternatives for patients with unique medical needs that are not met by available FDA-approved products, such as removing components to which a patient has an allergy, or by providing an alternate dosage form (e.g., turning a pill medication into a liquid for patients who cannot swallow).

Compounded Topical Pain Creams: Are They Safe and Are They Effective?

Effective pain therapy hinges on targeting specific mechanisms underlying an individual’s pain. Today, many manufactured pharmacological therapies approved by the FDA are available to treat acute and chronic pain. However, pain patients may have unique clinical needs (e.g., end-of-life care patients not being able to swallow a pill, concerns about drug-drug interactions), which suggests that pain creams may be a useful alternative or supplemental treatment approach.

However, for compounded topical pain creams, like other compounded medications, there is a significant lack of high-quality and well-controlled studies to demonstrate that these medications are as safe or effective as existing FDA-approved medications. The few active ingredients in compounded topical pain creams that have limited data suggesting they may be effective are already available in FDA-approved topical pain creams. The evidence-based rationale for the widespread use of these compounded medications is unclear.

Compounded Bioidentical Hormone Therapies (cBHT): Are They Safe and Are They Effective?

Much like compounded topical pain creams, the practice of compounding for bioidentical hormone therapies has largely expanded based on patient preference, rather than evidence of clinical utility for for these medications. A large proportion of patients using cBHT are women seeking treatment for menopausal symptoms. These therapies do not undergo the same rigorous testing to demonstrate their effectiveness as FDA-approved drug products (including FDA-approved bioidentical hormone products), nor has their safety been confirmed by high-quality and well-controlled clinical studies.

The Need for More Oversight

FDA approves a new drug for public use only after careful review of data from preclinical studies and human clinical trials. After a drug has been approved, FDA also requires follow-up surveillance to collect data on adverse events. The same is not true for compounded preparations. More oversight is needed at both the federal and state level to better address public health and clinical concerns about compounded medications.

As of February 2020, less than 80 of the tens of thousands of U.S. compounding facilities have voluntarily registered as large-scale 503B outsourcing facilities. These facilities are required to operate under higher regulation standards than 503A pharmacies or other facilities who have not voluntarily identified themselves.

The figure is intended to provide a general overview of the statutory and regulatory processes required of FDA-approved drug products and compounded drug preparations. The figure does not offer a complete summary of the complex regulatory framework for all drug products or compounded preparations. 503A compounding pharmacies are commonly independent, community pharmacies that dispense patient-specific medications on an as-needed basis. 503B outsourcing facilities are permitted to dispense large-scale, non-patient specific medications across state lines.

For more information, please see Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use, pg. 66-67 and The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use, pg 52.

More Research is Needed on Compounding Safety

As the field of personalized medicine continues to expand, government regulators, physicians, pharmacists, and patients all need a stronger research base to properly evaluate whether compounded preparations are safe to use and whether they have demonstrated clinical utility. This includes:

  • Accurate and consistent data on adverse health events
  • High-quality and well-controlled clinical research on safety and effectiveness of commonly compounded preparations
  • Research on new therapies that may work more effectively
  • Data on the impacts of genetic and lifestyle differences, such as smoking, drinking alcohol, and diet

Strategies for Improving Compounding Safety and Use

Until there is increased oversight, better data, and a demonstrated clinical need for widespread use of compounded preparations, the use of these medications should be restricted to limited circumstances. Patient preference should not be the sole driver for use. Instead, prescribers and compounders should ensure that patients’ decision making is informed by evidence-based health information and shared decision making.

Overview of Recommendations for Compounded Topical Pain Creams:

  • Exercise caution when prescribing or dispensing compounded topical pain cream preparations
  • Strengthen and expand the evidence base on the safety and effectiveness of ingredients commonly used in compounded topical pain creams
  • Require continued training for clinicians who prescribe compounded pain medication, and revise current educational requirements for those who compound
  • Increase state-level oversight of compounding

Overview of Recommendations for cBHT:

  • Restrict the use of cBHT preparations.
  • Review select bioidentical hormone therapies and dosage forms as candidates for the FDA Difficult to Compound List
  • Improve education for prescribers and pharmacists who market, prescribe, compound, and dispense cBHT preparations.
  • Additional federal and state-level oversight should be implemented to better address public health and clinical concerns regarding the safety and effectiveness of cBHT
  • Collect and disclose conflicts of interest
  • Strengthen and expand the evidence base on the safety, effectiveness, and use of cBHT preparations
Read Compounded Topical Pin Creams Report Read Compounded Bioidentical Hormone Therapy Report