P-051 - Nonmedical Use and Route of Administration of XTAMPZA® ER versus Other Oxycodone Medications (Extended- and Immediate-Release) in Adults Evaluated for Substance Use with the Addiction Severity Index-Multimedia Version (ASI-MV®)

Abstract Title: Nonmedical Use and Route of Administration of XTAMPZA^® ER versus Other Oxycodone Medications (Extended- and Immediate-Release) in Adults Evaluated for Substance Use with the Addiction Severity Index-Multimedia Version (ASI-MV^®)

Background: Prescription opioid medications with abuse-deterrent properties are products designated by the US Food and Drug Administration (FDA) as products that may meaningfully deter abuse, even if they do not fully prevent abuse¹. Opioid medications with abuse deterrent formulations (ADF) include technology expected to make manipulation more difficult and reduce use via nonoral routes (intranasal, inhalation, injection) which are associated with higher risk of life-threatening events/death². Compared with immediate-release (IR) formulations, extended-release (ER) products contain higher amounts of the active drug ingredient as the drug is intended to be released in the body over an extended period of time (up to 12 hours). When an ER mechanism is defeated, most or all of the active ingredient becomes immediately available, making the product particularly attractive for abuse. While all ER oxycodone products are required to be an ADF, not all products use the same formulation and may have different abuse deterrence effectiveness. A previous study compared oxycodone-containing products and found lower rates of XTAMPZA ER nonmedical use (NMU) and abuse via nonoral routes as compared to other ER oxycodone and IR oxycodone in adults evaluated for substance use after three years postmarket experience³. However, continued monitoring is warranted to ensure sustained effectiveness.

Purpose/Objectives: The purpose of this study was to estimate the real-world rate of nonmedical use (NMU) of XTAMPZA ER (an oxycodone ER opioid analgesic with abuse-deterrent properties) and comparator prescription oxycodone-containing products (other oxycodone ER products with abuse deterrent properties and oxycodone IR products) in a population of adult patients evaluated for substance abuse treatment with the standardized Addiction Severity Index – Multimedia Version (ASI-MV®) assessment tool.


Methods: This study compares NMU rates of XTAMPZA ER and other oxycodone medications among adults assessed for substance use with the ASI-MV. The ASI-MV is a validated computerized clinical intake assessment used to evaluate substance use and inform treatment planning within a network of substance abuse treatment centers and other evaluation settings. The study included ASI-MV assessments completed from 01 July 2016 (Q3 2016) through 31 December 2023 (Q4 2023). XTAMPZA ER was added to the ASI-MV tool on 17 September 2017. The primary outcome of the study was past 30-day NMU, overall and by routes of administration. NMU is defined as use in any way or for any other reason than as prescribed or use without the user’s own prescription. NMU includes misuse (used for therapeutic benefit but used in ways other than prescribed) and abuse (used for psychotropic effect or to get high).

Demographics, NMU rates, and route of administration were compared between the following study groups: (1) XTAMPZA ER, (2) other ER oxycodone, and (3) IR oxycodone. NMU rates were adjusted for drug utilization (per 1,000,000 dosage units dispensed) using data from IQVIA. Confidence intervals (95% CI) were used to determine statistically significant differences between study groups.


Results: Of the 341,851 assessments completed, 67,855 reported past 30-day NMU of any prescription opioid medication. Of those, 141 (0.2%) reported past 30-day NMU of XTAMPZA ER, 4,935 (7.3%) reported past 30-day NMU of other ER oxycodone, and 20,394 (30.1%) reported past 30-day NMU of an IR oxycodone product (groups are not mutually exclusive as NMU of more than one product can be reported in any given assessment). Study groups were similar in gender distribution (49-53% male) and age (greatest proportion 25-34 years).

Quarterly NMU drug utilization-adjusted rates of XTAMPZA ER ranged from 0.17 (95% CI 0.02-1.17) to 5.32 (95% CI 2.77-10.22) mentions per 1m dosage units dispensed, however only three quarterly rates were greater than 2.0 mentions per 1m dosage units dispensed. Quarterly NMU drug utilization-adjusted rates of other ER oxycodone ranged from 4.58 (95% CI 3.68-5.69) to 9.86 (95% CI 8.64-11.25) mentions per 1m dosage units dispensed. Other ER oxycodone quarterly NMU drug utilization-adjusted rates were statistically significantly higher than those of XTAMPZA ER from Q2 2018 through Q4 2023 and statistically significantly higher than IR oxycodone the duration of the study. Quarterly NMU drug utilization-adjusted rates of IR oxycodone ranged from 0.99 (95% CI 0.90-1.09) to 4.86 (95% CI 4.70-5.01) mentions per 1m dosage units dispensed. IR oxycodone quarterly rates were statistically significantly higher than XTAMPZA ER in 7 quarters. In no instance was the quarterly NMU rate of XTAMPZA ER significantly higher than the comparator groups.

Of the 141 reports of XTAMPZA ER NMU, 110 (78.0%) involved oral use: 75 (53.2%) reported swallowing intact and 35 (24.8%) chewing or dissolving prior to ingestion. Only 36 involved nonoral use: 24 (17.0%) intranasal, 4 (2.8%) inhalation, and 8 (5.7%) injection. Oral use was similar for other ER oxycodone (4,281; 80.1%) and lower for IR oxycodone (29,655; 71.2%). In contrast, nonoral use was significantly higher than XTAMPZA ER for other ER oxycodone (3,004; 56.2%) and IR oxycodone (25,006; 60.1%). Nonoral use for other ER oxycodone included 31.8% intranasal, 4.5% inhalation, and 20.0% injection. Nonoral use for IR oxycodone included 40.8% intranasal, 5.1% inhalation, and 14.1% injection.

Conclusions/Implications for future research and/or clinical care: This study demonstrates that after seven years on the US market, XTAMPZA ER continues to have a lower rate of NMU in a population of substance users compared to IR oxycodone and other ER oxycodone products which also have abuse deterrent labeling. Furthermore, the likelihood of high-risk nonoral use is over twice as high for other ER oxycodone and IR oxycodone products compared to XTAMPZA ER. These real-world data support the findings from premarket studies suggestive of effective XTAMPZA ER abuse deterrent properties in the postmarket setting.

References: ¹ United States Food and Drug Administration CDER: Abuse Deterrent Opioids—Evaluation and Labeling, Guidance for Industry. April 2015. Available at https://www.fda.gov/downloads/Drugs/Guidances/UCM334743.pdf. Accessed 03 June 2023.

²Green JL, Bucher Bartelson B, Le Lait MC, Roland CL, Masters ET, Mardekian J, Bailey JE, Dart RC. Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alc Dependence. 2017;175:140-145. https://doi.org//10.1016/j.drugalcdep.2017.01.039

³Green JL, Robbins RS, Dailey-Govoni T, Butler SF. Nonmedical use of Xtampza® ER and other oxycodone medications in adults evaluated for substance abuse treatment: real-world data from the Addiction Severity Index-Multimedia Version (ASI-MV®). Journal of Pain Research. 2021;14:1773-1783. https://doi.org/10.2147/JPR.S304805