WASHINGTON — While compounded topical pain creams have become an increasingly popular alternative to oral pain medications and opioids, there is a lack of scientific evidence to support their safety or effectiveness, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Many ingredients used in compounded topical pain creams are not approved by the U.S. Food and Drug Administration (FDA) to topically treat pain. Furthermore, patients may not be aware that compounded topical pain creams are not subject to the same level of quality testing and regulatory oversight as commercially available, FDA-approved topical pain treatments, the report says.                                                                                         

Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use identifies several opportunities to help address the public health concerns related to use of compounded topical pain creams. Its recommendations include improving federal and state oversight of safety measures; data collection and surveillance; and training and education for pharmacists and clinicians who compound, which is the practice of combining, mixing, or adjusting ingredients to create a tailored medication for a patient.

Compounded topical pain medications are used to treat conditions ranging from sports injuries and muscle aches, to arthritis, to pain associated with cancer and multiple sclerosis. They can be applied to the skin in the form of gels, creams, lotions, or ointments. Some of the Active Pharmaceutical Ingredients (APIs) used in compounded pain creams — including steroids, anesthetics (ketamine and lidocaine), and opioid agonists (tramadol) — have been FDA-approved for pain indications, but not specifically for topical use. Consequently, little is known about their profiles of safety and effectiveness when used alone or in combination with other APIs. This increases the risk of applying too little medication to achieve pain relief — or too much medication, which can result in overdose or severe toxicity if ingredients are absorbed into the bloodstream.

The committee that wrote the report reviewed 20 APIs included in compounded topical pain creams that are meant for application to healthy, intact skin. Of the 20 APIs reviewed, only three individual ingredients — doxepin, lidocaine, and naproxen — show potential evidence of effectiveness, it concluded.

“Nearly 50 million U.S. adults live with chronic pain, and with all the dangers of opioid use, many of them are looking for less invasive treatment options — including compounded topical pain creams,” said committee chair Debra Schwinn, president, Palm Beach Atlantic University. “Providers should exercise caution before prescribing a compounded preparation, and seek FDA-approved options for patients if possible.”

With the rise of mail and online pharmacies, consumers may not always receive pharmacist counseling on the risks associated with compounded preparations. The report recommends the National Association of Boards of Pharmacy (NABP) require compounding pharmacies to provide a standardized insert for all compounded topical pain creams, clearly outlining how much should be used, the APIs and inactive ingredients used, and the potential adverse effects.

Increasing Federal and State Regulation and Oversight

The NABP should require 503A compounding pharmacies – which produce compounded preparations for individual patients or in limited batch quantities – to report adverse events at the state level and to FDA’s MedWatch, the report recommends. In addition, FDA and a global standards-setting organization (such as U.S. Pharmacopeia, or USP) should collaboratively develop standard processes for testing APIs and inactive ingredients commonly used in compounded topical pain creams. Further, 503A compounding pharmacies should uniformly adopt USP standards to ensure the quality of dispensed preparations and minimize variation in practices. 

Improving Data Collection and Surveillance

Funding agencies, including the National Institutes of Health, and relevant patient advocacy organizations should support research initiatives to examine the safety and effectiveness of compounded topical pain creams. Priority research should include randomized, double-blind, placebo-controlled clinical trials with sufficient numbers of patients to study APIs and inactive ingredients used — both individually and combined — in compounded topical pain creams. More robust epidemiological data are also needed to identify the demographics of consumers, particularly geriatric, pediatric, and pregnant populations; the frequency of medication use; the medical conditions for which the preparations are used; and adverse events. 

Strengthening Training and Education for Prescribers
State boards of pharmacy and relevant health professional societies should support and incentivize more in-depth training on compounding in schools of medicine and pharmacy, as well as continuing education, the report says. Clinicians who prescribe topical pain creams should also seek state-level certification.

The study — undertaken by the Committee on the Assessment of the Available Scientific Data Regarding the Safety and Effectiveness of Ingredients Used in Compounded Topical Pain Creams — was sponsored by the U.S. Food and Drug Administration. The National Academies are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. 

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Stephanie Miceli, Media Officer
Office of News and Public Information
202-334-2138; e-mail news@nas.edu