National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Compounded
Topical Pain Creams

Review of Select Ingredients for Safety, Effectiveness, and Use

Debra A. Schwinn and Leigh Miles Jackson, Editors

Committee on the Assessment of the Available Scientific Data
Regarding the Safety and Effectiveness of Ingredients
Used in Compounded Topical Pain Creams

Board on Health Sciences Policy

Health and Medicine Division

A Consensus Study Report of

images

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by a contract between the National Academy of Sciences and the U.S. Food and Drug Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-67215-3
International Standard Book Number-10: 0-309-67215-5
Digital Object Identifier: https://doi.org/10.17226/25689
Library of Congress Control Number: 2020937383

Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

Copyright 2020 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Compounded topical pain creams: Review of select ingredients for safety, effectiveness, and use. Washington, DC: The National Academies Press. https://doi.org/10.17226/25689.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Image

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.

The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.

The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.

Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Image

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.

Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.

For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

COMMITTEE ON THE ASSESSMENT OF THE AVAILABLE SCIENTIFIC DATA REGARDING THE SAFETY AND EFFECTIVENESS OF INGREDIENTS USED IN COMPOUNDED TOPICAL PAIN CREAMS

DEBRA A. SCHWINN (Chair), President, Palm Beach Atlantic University (from April 2020); Professor, University of Iowa Carver College of Medicine (until April 2020)

STEPHEN BYRN, Professor, Purdue University

DIANA D. CARDENAS, Emeritus Professor and Chair, University of Miami Miller School of Medicine

BARBARA INSLEY CROUCH, Professor and Executive Director, Utah Poison Control Center, College of Pharmacy, University of Utah

EDMUND J. ELDER, Director, Zeeh Pharmaceutical Experiment Station, University of Wisconsin–Madison

JOHN T. FARRAR, Associate Professor of Epidemiology and Neurology, University of Pennsylvania Perelman School of Medicine

CARMEN GREEN, Professor, University of Michigan

FRIEDHELM SANDBRINK, National Program Director for Pain Management, U.S. Department of Veterans Affairs

VINOD P. SHAH, Expert Consultant, NDA Partners

JOYCE S. TSUJI, Principal Scientist, Exponent

CAROL S. WOOD, Research Staff Scientist, Oak Ridge National Laboratory

National Academy of Medicine Fellow

DIMA QATO, Assistant Professor, University of Illinois at Chicago

Study Staff

LEIGH MILES JACKSON, Study Director

CLAIRE GIAMMARIA, Associate Program Officer

ANDREW MARCH, Research Associate

JUSTIN JONES, Senior Program Assistant

DANIEL CESNALIS, Financial Officer (until June 2019)

ANNA ISABEL CAMILO JAVIER, Financial Officer (until January 2020)

VICTOR STEWART, Financial Officer (from February 2020)

MARIAM SHELTON, Program Coordinator (until August 2019)

BRIDGET BOREL, Program Coordinator (from October 2019)

ANDREW M. POPE, Senior Director, Board on Health Sciences Policy

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Consultants

S. NARASIMHA MURTHY, Professor of Pharmaceutics and Drug Delivery, University of Mississippi

ANNA NICHOLSON, Science Writer, Doxastic LLC

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by ELI Y. ADASHI, Brown University, and DAVID L. EATON, University of Washington. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Preface

Pain is complex and often hard to treat. Acute and/or chronic pain affects millions of individuals each year and is associated with morbidity and increased health care use. Once pain became regarded as the “fifth vital sign,” clinicians, patients, hospitals, and health systems began to more vigorously treat all types of pain in order to meet a “no pain” patient satisfaction standard, often with increasing use of medications (e.g., opioid analgesics, nonsteroidal anti-inflammatories, adjuvants) and other modalities. In retrospect, return to functional activity is a better goal because zero pain is unrealistic in many medical situations.

Clinicians who treat pain recognize that elucidation of the specific mechanism underlying an individual’s pain is essential for rational pain therapy. As a result, a variety of oral medications have been developed over the years to target various pain mechanisms. However, not everyone can tolerate specific oral medications, given coexisting diseases and age-related changes, and there is a general desire to limit systemic effects of drugs whenever possible. In addition, currently available oral medications do not effectively treat all pain scenarios. In recent years this has led to emergence of a host of alternative approaches to treating pain (providing analgesia). One such approach is topical analgesia.

Topical application of analgesics has two possible roles. First, skin-based drug application provides an alternative approach to achieve systemic levels of medication, exemplified by the fentanyl patch; however, this first approach is not the focus of this report. A second role involves topical analgesics in the form of gels, patches, or creams applied to the skin to deliver pain medication to a localized area of the body. In theory, topically

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

applied pain medication provides analgesia near the skin (locally) while minimizing systemic absorption (uptake into the blood with circulation to the entire body). There are many potential advantages of using topical approaches to treating pain, although it would be an error to consider a drug safe simply because it is being delivered through the skin; this was elegantly demonstrated in a recent study showing sunscreen lotion chemicals applied to the skin are absorbed systemically at potentially high enough levels to be of concern,1 as well as in an older study2 that demonstrated how permeable skin can be to organic compounds. Nonetheless, skin does provide a formidable barrier to entry of active ingredients for pain therapy, so these drugs are often applied in much higher concentrations than would be used orally. While this is not a problem for healthy intact skin in most adults, it can create life-threatening situations in cases where pain therapies are topically applied to skin that is not normal (e.g., skin or diaper rash, thin skin at extremes of age, burns) or when applied to large areas relative to body size. Because skin is such a formidable barrier, topical pain creams often contain enhancers, or chemicals specifically designed to help move a drug from the surface through the skin (epidermis and dermis) to regional areas below with a goal of reaching a muscle group or joint for treating pain. Of note, when active drug ingredients move beyond the skin to subdermal regional locations, they are brought in contact with the systemic circulation and some amount of drug will be absorbed into the central circulation.

Because the U.S. Food and Drug Administration (FDA) has only approved a few topical analgesics, pharmacies have filled in the gap by providing compounded topical pain creams. Compounding is a traditional part of pharmacy practice where pharmacists prepare drugs in alternate dosages or vehicles to support the specific clinical need of individual patients; for example, a cancer patient who cannot swallow tablets or capsules might have a pharmacist produce or compound a liquid form of the drug that could be swallowed more easily. Because of the long historical roots centered on small independent compounding pharmacies, the U.S. Congress has permitted most compounded preparations to be made with minimal FDA oversight, as compared to FDA-approved drug products.3

___________________

1 Matta, M. K., R. Zusterzeel, N. R. Pilli, V. Patel, D. A. Volpe, J. Florian, L. Oh, E. Bashaw, I. Zineh, C. Sanabria, S. Kemp, A. Godfrey, S. Adah, S. Coelho, J. Want, L. A. Furlong, C. Ganley, T. Michele, and D. G. Srauss. 2019. Effect of sunscreen application under maximal use conditions on plasma concentration of sunscreen active ingredients: A randomized clinical trial. JAMA 321(21):2082–2091.

2 Feldmann, R. J., and H. I. Maibach. 1970. Absorption of some organic compounds through the skin in man. Journal of Investigative Dermatology 54(5):399–404.

3 This text has changed since the prepublication release of this report. Here and in other instances throughout the report, “commercially available product(s)” was replaced with “FDA-approved drug product(s).”

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

However, over the past two decades, there has been a substantial increase in both supply and demand for compounded medications. Consequently, an increasing fraction of drugs used in the United States are created without FDA oversight for quality, safety, efficacy, labeling, and/or postmarketing surveillance. Moreover, a growing number of reports of patients who have encountered harm using compounded preparations, including topical pain creams, highlights growing concerns.

Adding further complexity, given the global nature of drug and chemical production and distribution today, sources and quality of many products have become significant issues. As such, each individual compounding pharmacy is tasked with checking active ingredients used in compounded products for potency, quality, and lack of contaminants, a process that is impractical for many smaller pharmacies. Current compounded pain creams often contain more than one active ingredient, with many containing four to six drugs, creating the potential for combined toxicity and drug-to-drug interactions. It has been suggested by proponents of topical pain creams that combinations of active ingredients are present in order to target different underlying mechanisms of pain; however, it is interesting to note that some ingredients used today are primarily effective on central nervous system (CNS) pain pathways and not skin or localized regions near skin. Moreover, patients are often charged by the number of active ingredients included in their compounded preparations, which has led to insurance-related concerns regarding cost inflation and possible fraud.

In addition to considering active pharmaceutical ingredients to be compounded into a topical pain cream, the formulation of a topical product requires selection of an appropriate vehicle. There are a growing number of ointments and creams that can be used, with very little publicly available data to distinguish one from another. To facilitate ease of pharmacists compounding topical pain creams, several cream bases are now commercially available, some of which contain proprietary ingredients such as skin penetration enhancers and other chemicals designed to enhance ease of application and attractiveness of the final product to patients. The result is that pharmacists, prescribers, and patients are often not aware of all that is present in the cream and the potential side effects of its components. Because pain drug efficacy depends on relative penetration of active drugs through the skin, in addition to drug concentration, efficacy may vary depending on the cream base used. For best efficacy, each active ingredient concentration should be optimized and tested within a given cream base, an effort that would be costly and time consuming to do for every additional ingredient added to such a preparation.

Finally, given the interprofessional nature of clinical practice today, the pharmacist is often viewed by clinicians as the expert on the team in terms of drug therapy. So, when lists of prefilled prescription forms or

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

menus for compounded pain creams are faxed to clinicians for marketing purposes, there is a general expectation on the clinician’s part that testing has occurred and that each combination has been shown to be effective. Even when this is not the case, once the clinician signs the form requesting a set of active ingredients and base cream for a patient, his or her signature provides the legal prescription that guides creation of the compounded pain cream; hence, ultimately it is the clinician who bears responsibility for having chosen to include specific or numerous ingredients. In this setting, there have also been cases of fraudulent prescribing.

Given this complicated backdrop, and the increasing use of these products, FDA requested that the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine (the National Academies) assess available scientific data regarding safety and effectiveness of ingredients used in compounded topical pain creams. Specifically, this committee was charged with identifying individual ingredients that scientific data support as being safe and effective to treat pain topically, describing concentrations and combinations of ingredients that may raise significant safety issues, and defining the level of expected benefit for various ingredients given their likelihood of being absorbed through the skin. Based on this information, the committee was ultimately tasked with making recommendations for how the available scientific data on safety and efficacy informs use of compounded topical pain creams to treat patients going forward. In making its deliberations, the committee specifically sought information and comments from the general public, as well as various stakeholders (including, but not limited to, patients, clinicians, compounding pharmacists, regulators, pain advocacy organizations, and government payers) as well as examining the scientific literature.

The committee is composed of an outstanding panel of national experts with broad related scientific expertise. In addition to the committee, such a detailed exploration of scientific literature and generation of the final consensus study report would not have been possible without the strong support of outstanding staff members from the National Academies, specifically Leigh Miles Jackson (study director), Claire Giammaria (associate program officer), Andrew March (research associate), Justin Jones (senior program assistant), and Anna Nicholson, our talented editor and writer. Thank you to everyone who participated in this timely and important report.

Debra A. Schwinn, Chair
Committee on the Assessment of the Available
Scientific Data Regarding the Safety and Effectiveness of Ingredients Used in Compounded Topical Pain Creams

Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Acknowledgments

The committee takes this opportunity to recognize the many individuals and organizations who so generously gave their time and expertise to inform its work.

To begin, the committee would like to thank the sponsor of this study, the U.S. Food and Drug Administration (FDA), for its guidance and support. The committee also greatly benefited from the discussions with individuals who attended and made their public presentations (see Appendix B). The committee is thankful for the many contributions of these individuals.

The committee could not have done its work without the support and guidance provided by the National Academies of Sciences, Engineering, and Medicine (the National Academies) project staff: Leigh Miles Jackson, study director; Claire Giammaria, associate program officer; Andrew March, research associate; and Justin Jones, senior program assistant. We appreciate Victor Stewart for his financial assistance on this project, and gratefully acknowledge Carolyn Shore and Andrew Pope of the Board on Health Sciences Policy for the guidance he provided throughout this important study.

Many other staff within the National Academies provided support to this project in various ways. The committee would like to thank the executive office staff of the Health and Medicine Division, as well as Dorothy Zolandz, Bettina Seliber, and Taryn Young for the management of the report review and publication process. We would like to thank Jorge Mendoza-Torres, Rebecca Morgan, and the National Academies Research Center staff for their assistance in the committee’s research efforts, as well as the National Academies Press staff.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

This committee is grateful to the research and writing consultants that generously contributed to this body of work. We thank the committee’s consultant S. Narasimha Murthy (University of Mississippi) for his invested time and support of this study. We thank American Association of Poison Control Centers, American Chronic Pain Association, American Pharmacists Association, FDA, Institute for Neuropathic Pain, Massachusetts Boards of Pharmacy, National Association of Boards of Pharmacy, and Professional Compounding Centers of America for their generous submission of data and resources, and for the context and perspective they provided.

Finally, the committee is indebted to Anna Nicholson (Doxastic LLC) for her valuable commissioned work, and Mark Goodin for his editorial assistance in preparing this report.

Page xviii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

This page intentionally left blank.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

6-2 Summary of Research Findings on Clonidine in Compounded Topical Pain Creams

6-3 Summary of Research Findings on Carbamazepine in Compounded Topical Pain Creams

6-4 Summary of Research Findings on Gabapentin in Compounded Topical Pain Creams

6-5 Summary of Research Findings on Topiramate in Compounded Topical Pain Creams

6-6 Summary of Research Findings on Baclofen in Compounded Topical Pain Creams

6-7 Summary of Research Findings on Cyclobenzaprine in Compounded Topical Pain Creams

6-8 Summary of Research Findings on Orphenadrine in Compounded Topical Pain Creams

6-9 Summary of Research Findings on Nifedipine in Compounded Topical Pain Creams

6-10 Summary of Research Findings on Cannabidiol in Compounded Topical Pain Creams

6-11 Summary of Research Findings on Ketamine in Compounded Topical Pain Creams

6-12 Summary of Research Findings on Bupivacaine in Compounded Topical Pain Creams

6-13 Summary of Research Findings on Lidocaine in Compounded Topical Pain Creams

6-14 Summary of Research Findings on Memantine in Compounded Topical Pain Creams

6-15 Summary of Research Findings on Meloxicam in Compounded Topical Pain Creams

6-16 Summary of Research Findings on Naproxen in Compounded Topical Pain Creams

6-17 Summary of Research Findings on the Use of Tramadol in Compounded Topical Pain Creams

6-18 Summary of Research Findings on Dexamethasone in Compounded Topical Pain Creams

6-19 Summary of Research Findings on Amitriptyline in Compounded Topical Pain Creams

6-20 Summary of Research Findings on Doxepin in Compounded Topical Pain Creams

6-21 Summary of Research Findings on Pentoxifylline in Compounded Topical Pain Creams

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

FIGURES

2-1 Process of developing an integrative pain treatment plan

4-1 Comparison of select steps within the statutory and regulatory processes for FDA-approved drug products and compounded drug preparations

4-2 Geographic distribution of 503B outsourcing facilities throughout the United States

4-3 Variability in state requirements for 503A compounding pharmacy compliance with USP <795> and <797> standards

5-1 Anatomy of skin

5-2 Routes of systemic absorption after topical application of a drug

5-3 Structure of stratum corneum

5-4 Transport of drugs through the layers of the skin

7-1 Sample prescription form distributed by a local pharmacy to physician offices in February 2019

7-2 Growth in Medicare Part D spending on compounded drugs by form (2006–2015)

TABLES

3-1 Sample of Reported Pain Conditions Treated with Compounded Topical Pain Creams

3-2 FDA-Approved and Off-Label Indications Limited to Pain Indications for Which Topical Pain Creams Are Often Used

5-1 Summary of the Physiochemical Properties Affecting Skin Absorption of Select Active Ingredients Commonly Used in Compounded Topical Pain Creams

5-2 The Amount of Drug Absorbed Across the Human Cadaver Skin from Topical Pain Creams

5-3 The Amount of Drug Absorbed Across the Human Cadaver Skin from Topical Pain Creams with Lipoderm and Lipoderm ActiveMax

5-4 Compendial Excipients from USP-National Formulary 19

5-5 Listed Excipients in Select Compounded Topical Pain Cream Formulations Described on Public Websites

5-6 Listed Components in Lipoderm ActiveMax from Patent US2013/0085171

Page xxii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page xxiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×

Acronyms and Abbreviations

ACCP American College of Clinical Pharmacy
API active pharmaceutical ingredient
CBD cannabidiol
CDC Centers for Disease Control and Prevention
CIPN chemotherapy-induced peripheral neuropathy
CNS central nervous system
CRPS complex regional pain syndrome
DESI Drug Efficacy Study Implementation
DMSO dimethyl sulfoxide
FAERS FDA’s Adverse Event Reporting System
FDA U.S. Food and Drug Administration
FDCA Federal Food, Drug, and Cosmetic Act
GTN glyceryl trinitrate
HCl hydrochloride
HHS U.S. Department of Health and Human Services
MRI magnetic resonance imaging
NABP National Association of Boards of Pharmacy
NF National Formulary
Page xxiv Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
NPDS National Poison Data System
NSAID nonsteroidal anti-inflammatory drug
PCCA Professional Compounding Centers of America
PLC piroxicam, lidocaine, and cyclobenzaprine hydrochloride
PLO pluronic lecithin organogel
PWT paw withdrawal threshold
RCT randomized controlled trial
THC tetrahydrocannabinol
USP United States Pharmacopeia
VAS visual analog scale
w/w weight per weight
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R1
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R2
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R3
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R4
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R5
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R6
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R8
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R9
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R10
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R11
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R13
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R14
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R15
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R16
Page xvii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R17
Page xviii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R18
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R19
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R20
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R21
Page xxii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R22
Page xxiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R23
Page xxiv Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Page R24
Next: Summary »
Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use Get This Book
×
Buy Paperback | $85.00 Buy Ebook | $69.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Pain is both a symptom and a disease. It manifests in multiple forms and its treatment is complex. Physical, social, economic, and emotional consequences of pain can impair an individual’s overall health, well-being, productivity, and relationships in myriad ways. The impact of pain at a population level is vast and, while estimates differ, the Centers for Disease Control and Prevention reported that 50 million U.S. adults are living in pain. In terms of pain’s global impact, estimates suggest the problem affects approximately 1 in 5 adults across the world, with nearly 1 in 10 adults newly diagnosed with chronic pain each year.

In recent years, the issues surrounding the complexity of pain management have contributed to increased demand for alternative strategies for treating pain. One such strategy is to expand use of topical pain medications—medications applied to intact skin. This nonoral route of administration for pain medication has the potential benefit, in theory, of local activity and fewer systemic side effects. Compounding is an age-old pharmaceutical practice of combining, mixing, or adjusting ingredients to create a tailored medication to meet the needs of a patient. The aim of compounding, historically, has been to provide patients with access to therapeutic alternatives that are safe and effective, especially for people with clinical needs that cannot otherwise be met by commercially available FDA-approved drugs.

Compounded Topical Pain Creams explores issues regarding the safety and effectiveness of the ingredients in these pain creams. This report analyzes the available scientific data relating to the ingredients used in compounded topical pain creams and offers recommendations regarding the treatment of patients.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!