Amelia L. Perscio, PharmD, MBA

Abuse-deterrent formulations (ADFs) of opioid medications were first marketed in 2010 when a reformulated version of OxyContin (extended-release oxycodone) was

released at the mandate of the FDA in an effort to address the nationwide opioid epidemic.

This product was created with both chemical and physical barriers to its manipulation.

 The intention was to reformulate traditional opioid medications in ways that would make it more difficult to chemically and physically alter the delivery of their active pharmaceutical ingredient in an effort to reduce the potential for abuse. These efforts were particularly directed at extended-release and long-acting formulations, which are especially attractive to abusers of opioid medications because of the high-milligram content in a single-dose unit.

Prescription opioid abuse is not limited to taking intact tablets by mouth. Rather, those who abuse prescription opioids chew, crush, dissolve, and otherwise manipulate the tablets to take them intranasally, intravenously, orally, via inhalation, and by other routes of administration. By altering the route of administration and delivery systems, users are able to achieve different pharmacokinetics with preference toward increasing peak concentration and decreasing time to peak. Manipulation causes a “dose-dumping” effect in which higher serum levels are achieved more rapidly, resulting in enhanced psychoactive effects.

 Because of this, abuse via intranasal and intravenous routes is associated with more severe individual and societal risks.

Abuse-deterrent formulations have been created with alternate bases or harder outer shells, or coformulated with opioid antagonists to make manipulation and abuse more difficult.

 No amount of reformulation can completely deter all forms of manipulation, eliminate the potential for drug diversion, or deter users from taking more medication than prescribed. But the creation of ADFs was intended only as 1 component of a multifaceted approach to reducing opioid abuse and misuse.

Since the introduction of ADFs, the products have only gradually seen enough use in the market to preliminarily demonstrate decreased diversion and rates of intentional abuse.

 However, there is a dearth of knowledge regarding patients with chronic pain and their experiences with and opinions about ADFs. Further, those patients and their caregivers have historically reported concerns regarding the stigma associated with chronic opioid therapy. There is potential for further apprehension

and stigma associated with opioids in general and with the prescription of ADFs in particular—specifically, being labeled or thought of as an abuser. Health care providers, in turn, may be concerned about patients having a false sense of security when they issue a prescription for an ADF instead of a traditional opioid formulation.

The American Chronic Pain Association (ACPA), with support from Collegium Pharmaceutical, conducted an anonymous needs assessment/survey of ACPA members to gather information on patient experience with ADFs and their knowledge and perceptions about the medications. Until this point, patients’ knowledge and opinions regarding ADFs had not been explored. Of the 1154 respondents to the survey, 936 completed it in full. As participants were recruited through the ACPA and more than 98% of them were people living with chronic pain, it is likely that they had a higher baseline knowledge regarding opioids and safe medication practices than the general population. Therefore, conclusions about the generalizability of survey results should be filtered through this lens.

The survey addressed patients’ knowledge on topics ranging from the existence of ADFs to safety and tampering. Further questions assessed patients’ behaviors and beliefs associated with ADFs. Respondents were stratified based on whether they were currently prescribed an ADF, and additional questions were posed to those patients with the goal of assessing their actual use. More than half of the survey respondents had never heard of an ADF. Therefore, 1 of the most significant findings of this study is a large knowledge gap regarding ADFs in the community of people living with pain.

Notably, the vast majority of respondents from both groups believed that it is not safe to take more ADFs than prescribed or to share an ADF with others. Most respondents who are currently prescribed an ADF reported that they do not crush, cut, or dissolve their tablets in water, whereas respondents not currently prescribed an ADF were more likely to report that they did not know whether tablets could be crushed, cut, or dissolved. Importantly, most respondents who are prescribed an ADF answered that they did not feel their prescriber was concerned about possible abuse when they prescribed the ADF. Those who take an ADF were divided as to

whether it is as effective as other opioids they have been prescribed.

This survey and an educational video have begun to fill a void in the literature regarding patients with chronic pain and their beliefs, experiences, and knowledge about ADF opioid medications. Certainly, some respondents voiced negative attitudes about incurring additional costs for ADFs when they do not personally think they are at risk for abuse or manipulation of the dose form. Others worried about the stigma, wondering if their physicians felt they were abusers. These views were not universal, however, and some respondents understood the potential need for ADFs in the context of continuing concerns related to the opioid epidemic. Thus, a potential takeaway for those who prescribe or dispense ADFs is that these patients are not uniformly concerned with stigma or as negatively inclined toward ADFs as some clinicians have thought. Rather, any apprehension or misgivings on the part of patients could be attributable to a lack of knowledge. This can be managed through individualized education and sensitivity to the patients’ pre-existing attitudes.

Clinicians can also be advised that both groups of patients were largely aware that they should not take more ADFs than prescribed nor should they share their ADFs with others. This advice could serve to assuage some concern for the potential false sense of security that some providers fear when prescribing ADFs.

The authors conclude that, concerning ADFs, patients who suffer from chronic pain have neither a commonly held negative view nor a commonly held positive view, and that this population respects and understands opioid safety, overall. These findings support the notion that ADFs can be a valuable part of a comprehensive approach to managing the opioid epidemic. As practitioners on the frontlines of both patient and provider education, pharmacists are poised to impart this important information regarding ADFs to their medical colleagues and patients alike.

, is a PGY-2 pain and palliative care pharmacy resident at the Albany Stratton VA Medical Center in Albany, New York.

Jeffrey Fudin, PharmD, FCCP, FASHP, FFSMB

, is chief executive officer and founder of Remitigate, LLC and the owner and managing editor of paindr.com. He is also an adjunct associate professor at Western New England University College of Pharmacy and Health Sciences in Springfield, Massachusetts, an adjunct associate professor of pharmacy practice and pain management at Albany College of Pharmacy and Health Sciences in Albany, New York, and the director of the PGY-2 pain residency at Albany Stratton VA Medical Center.

 is the founder and chief executive officer of the American Chronic Pain Association in Rocklin, California.

, is a research assistant and evaluations specialist at the Native American Rehabilitation Association of the Northwest, Inc, in Portland, Oregon.

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Articles

Pharmacists can extend education to prescribers and provide important guidance on abuse-deterrent opioid formulations.