|Theresa A. Cassidy, Jared Beaumont, Veronica Urdaneta, Simon H. Budman, Stephen F. Butler|
Presented at PAINWeek 2014
FDA Guidelines released in January 2013 on evaluating abuse-deterrent formulations (ADFs) recommend direct comparison of prevalence of abuse for the ADF against historical baseline levels of non-ADF comparators. This analysis assumes a level of stability in the prescription opioid market prior to and following introduction of the ADF. However, introduction of ADF opioid products occurred in conjunction with the introduction of new non-ADF opioids (including brand and generic formulations) creating a dynamic landscape or “abuse ecology” in which abusers adapt and respond to new products as well as ADF vs. non-ADF alternatives for abuse. A reformulated version of extended-release (ER) oxymorphone designed to be crush-resistant (OPANA® ER – oxymorphone hydrochloride extended-release tablets; Endo Pharmaceuticals Inc., Malvern, PA) became commercially available in February 2012, concurrent with the cessation of production and diminishing supply of the original (non-ADF) brand formulation of this product.
Existence of the original brand as well as new generic ER and immediate-release (IR) oxymorphone formulations offer potential non-ADF alternatives for abuse of oxymorphone ER. A simple pre-post comparison of abuse and route of administration (ROA) profiles assumes that abuse of the original product would remain unchanged in the time period following introduction of the ADF. To examine this assumption, we reviewed abuse and route of administration patterns for both original and reformulated ER oxymorphone, and generics after introduction of crush-resistant ER oxymorphone during an 18-month period (October 2012 through March 2014).
Data were collected during October 2012 through March 2014 from a sample of 77,175 adults assessed for substance abuse problems and treatment planning at centers in the U.S. using surveillance data from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®). Individuals were assessed using the Addiction Severity Index-Multimedia Version (ASI-MV®), a standardized clinical interview that collects self-reported data on past 30-day abuse of illegal substances and prescription medications from adults during treatment admission and planning.
Estimates of abuse prevalence for reformulated crush-resistant oxymorphone ER and other categories
of oxymorphone (both ER and IR formulations) were measured as the proportion of abuse reported within the past 30 days among the total study sample of those assessed for substance abuse treatment and adjusted for prescription volume. ROA patterns were examined via calculating the percentage of individuals who reported abuse via a specific ROA among only those individuals who reported past 30-day abuse of the product or compound of interest (i.e., reformulated oxymorphone ER, original oxymorphone ER, generic oxymorphone ER). Abuse was defined as any nonmedical use of a prescription opioid product.
During the 18-month period examined (October 2012 – March 2014), abuse of reformulated oxymorphone ER per assessments and per prescriptions dispensed was higher than historical baseline abuse for original oxymorphone ER (1.03 versus 0.81 cases per 100 assessments; 86.76 versus 70.84 cases per 100,000 prescriptions). After market introduction of an ADF oxycodone ER product, abuse of original oxymorphone ER increased to a maximum of 1.94 cases per 100 assessments in Q4 2011 and then started to decline coinciding with introduction of reformulated oxymorphone ER. Also, during the past 18 months, abuse prevalence for reformulated oxymorphone ER was lower than generic formulations of oxymorphone ER (0.98 versus 1.03 cases per 100 assessments) and for any non-ADF
brand or generic formulations of oxymorphone ER (1.44 cases per 100 assessments). Per prescriptions dispensed, abuse prevalence for reformulated oxymorphone ER (83.43 cases per 100,000 prescriptions dispensed) was lower than non-ADF generic formulations of oxymorphone ER (264.88 cases per 100,000 prescriptions dispensed) and any non-ADF brand and generic oxymorphone ER (336.03 cases per 100,000 prescriptions dispensed). ROA patterns indicate that reformulated oxymorphone ER was mostly abused via injection (64%) with lower percentages of oral
abuse (22%) and snorting (21%) while non-ADF ER oxymorphone formulations (both brand and generic) indicated lower injection (36%) and a greater frequency of snorting (63%).
Evaluating the public health impact of ADFs should take into account the current market environment and dynamic “abuse ecology” for prescription opioids. Given market changes for oxymorphone products, comparison of abuse patterns of reformulated oxymorphone ER to historical baseline levels alone may not provide the most meaningful evaluation of abuse of this product. In the current environment, data indicate abuse of reformulated oxymorphone ER is lower than non-ADF oxymorphone ER formulations with changes in ROA patterns suggesting lower frequency of snorting but a higher percentage of abuse via injection for reformulated oxymorphone ER compared to other nonADF oxymorphone ER products.