Sustained Risk Reduction of Severe Clinical Outcomes Following Misuse/Abuse of XTAMPZA ER as Compared to Other Prescription Opioids

Treatment plans for pain therapy must address clinical needs while minimizing risk of potential misuse/abuse of prescription opioids. Currently available prescription opioid medications include immediate-release (IR) and extended-release (ER) formulations, some of which have abuse deterrent properties as determined by FDA. ER opioid medications are of particular concern for misuse/abuse because these formulations contain higher concentrations of active drug, which is especially dangerous when used via nonoral routes of administration (snorting or injecting)¹. Recent studies suggest decreased risk of misuse/abuse via non-oral routes are associated with the use of abuse deterrent formulations (ADFs)^2-5. Ongoing surveillance is necessary to monitor the sustainability of both the reduced risk of misuse/abuse and improved clinical outcomes found with ADFs as they become more commonly used in pain treatment plans.

Purpose/Objectives: The purpose of this study was to evaluate the prevalence of misuse/abuse, route of administration, and clinical outcomes among exposure data reported to the National Poison Data System (NPDS) for four different groups of prescription opioids: XTAMPZA ER, other ER oxycodone, other ER opioids for analgesia, and IR oxycodone. XTAMPZA ER is an ER oxycodone medication with ADF labeling. Other ER oxycodone products are also ADF medications but use a different technology/platform than XTAMPZA ER. The other ER opioids for analgesia and IR oxycodone groups are comprised almost exclusively of non-ADF medications.

Method:

Using NPDS data (01January2019 - 31December2022), frequency of misuse/abuse exposures and clinical outcomes were compared between XTAMPZA ER, other ER oxycodone (oral solid dosage forms of ER oxycodone excluding XTAMPZA ER), other ER opioids for analgesia (oral solid dosage forms of ER formulations of hydrocodone, oxymorphone, hydromorphone, morphine), and IR oxycodone (oral solid dosage forms). For purposes of this study, misuse/abuse exposures included any case documented as intentional misuse (therapeutic intent), intentional abuse (to get high or for other psychotropic effect), or intentional unknown (intentional exposure but not known if misuse or abuse). Demographics, route of administration, hospital admission, and medical outcome were evaluated with frequencies and rates. Relative risk of major (life-threatening) effect/death and hospital admission (with 95% confidence intervals) were calculated using XTAMPZA ER as the reference medication.

Results:

Misuse/abuse was reported in 32/301(10.6%) of XTAMPZA ER, 668/2,159(30.9%) of other ER oxycodone, 249/1,487(16.7%) of other ER opioids for analgesia, and 5,149/17,694(29.1%) of IR oxycodone cases. No XTAMPZA ER case involved a nonoral route compared to 19.3% of other ER oxycodone, 11.2% of other ER opioids for analgesia, and 18.9% of IR oxycodone. Compared to XTAMPZA ER, the relative risk of a major effect/death was 3.51 (CI 1.19-10.37) higher for other ER oxycodone and 3.59 (CI 1.22-10.54) higher for IR oxycodone and the relative risk of hospitalization was 2.60 (CI 1.14-5.89) higher for other ER opioids for analgesia.

Conclusions: This study suggests that XTAMPZA ER (an ADF ER oxycodone medication) may have a reduced risk of misuse/abuse than opioid medications compared in this study. Exposures to XTAMPZA ER reported to US poison centers were less likely to involve misuse/abuse than the opioid medications included in the other three study groups and no XTAMPZA ER exposure reported use by a nonoral route of administration, the routes associated with the highest risk for severe clinical outcomes. Life-threatening events and death were significantly less likely to occur with exposure to XTAMPZA ER than for exposure to other ER oxycodone and IR oxycodone medications. Opioid overdose has placed a significant burden on the US healthcare system. These data suggest that hospitalization is significantly less likely following an exposure to XTAMPZA ER as compared to other ER opioids used for analgesia. Consistent with previous reports, selection of opioid medications, taking into account their therapeutic effectiveness as well as their associated abuse profiles, may help healthcare providers balance patient needs for pain therapy and mitigation of opioid misuse/abuse in the clinical setting.

References: 1Green JL, Bucher Bartelson B, Le Lait MC, Roland CL, Masters ET, Mardekian J, Bailey JE, Dart RC (2017). Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alc Dependence. 175, 140-145. https://doi.org//10.1016/j.drugalcdep.2017.01.039
2Green JL, Robbins RS, Dailey-Govoni T, Butler SF (2021). 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. 14:1773-1783. https://doi.org/10.2147/JPR.S304805
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5Rodriguez RD, Dailey Govoni T, Rajagopal V, Green JL. Evaluating the effectiveness of reformulated extended-release oxycodone with abuse-deterrent properties on reducing non-oral abuse among individuals assessed for substance abuse treatment with the Addiction Severity Index-Multimedia Version (ASI-MV). Current Medical Research and Opinion 2023. http://doi.org/10.1080/03007995.2023.2178080