Due to the lack of evidence on the safety or effectiveness of the ingredients used in compounded topical pain cream products, caution should be exercised when prescribing or dispensing these preparations, according to a consensus study report of the National Academies of Sciences, Engineering, and Medicine (NASEM).
To get a better understanding of which ingredients are supported by scientific evidence and which may be associated with significant safety concerns, the FDA requested that the NASEM analyze available data to evaluate the safety and effectiveness of compounded topical pain creams.
According to the report, the majority of these products contain multiple active pharmaceutical ingredients (APIs). Although at least 1 ingredient in these preparations is typically found in a topical pain cream that has been approved by the Food and Drug Administration (FDA), other ingredients included in these products may have only been approved for non-topical administration or non-pain-related indications.
Additionally, similar to other compounded drugs, compounded topical pain creams have not been assessed for safety, efficacy, and quality or approved by the FDA. “NASEM’s report concludes, among other things, that there is limited evidence to support the use of compounded topical pain creams in the general adult population, and inadequate data to support conclusions regarding the safety of ingredients in these products gives rise to a substantial public health concern,” the Agency stated.
While compounded topical pain preparations may play a limited role in pain management for certain patients with specific needs, the authors of the report noted several “critical areas of concern” surrounding the safety and efficacy of these agents for general use. The first area of concern highlights the lack of both evidence supporting efficacy claims as well as knowledge regarding the potential for systemic absorption/toxicity for the majority of APIs used in topical pain cream products.
A review of 20 active APIs often used in the preparation of topical pain creams showed that only 3 single agents (doxepin, lidocaine, naproxen) and 1 drug combination (high dose pentoxifylline/clonidine) had some evidence demonstrating effectiveness. However, the authors stated that additional research is needed to support the claim and conclusions on safety could not be made due to inadequate data.
The second area of concern, which involves the formulation and dispensing of these preparations, highlights the inadequacy in training, protocols, and guidance for pharmacists and prescribing clinicians to guarantee the safe and effective delivery of these products. To improve upon this, the expert panel recommended continued training and a revision of current educational requirements for those who compound.
The third area of concern discussed in the report highlights the gaps between state and federal regulation, management, and surveillance of products not approved by the FDA. Here, the authors recommended additional state-level oversight over compounding pharmacies.
“In context of the recent rise in supply and demand of compounded preparations, lack of evidence regarding systemic absorption of ingredients used in compounded topical pain creams gives rise to a substantial public health concern,” the authors concluded. They added that, “the few APIs that show potential effectiveness in compounded topical pain creams […] are already available in FDA-approved topical products used to treat pain.”
Schwinn DA, Jackson LM, et al; National Academies of Sciences, Engineering, and Medicine. Compounded topical pain creams: Review of select ingredients for safety, effectiveness, and use (Uncorrected proofs published online May 13, 2020). Washington, DC: The National Academies Press. doi: org/10.17226/25689.