The Comparative Pharmacokinetics of Physical Manipulation by Crushing of Xtampza ^® ER Compared with OxyContin ^®

Abstract

Aim:To further characterize the pharmacokinetics of Xtampza R ER. Subjects & methods:This was an openlabel, randomized, active-controlled, five-treatment, five-period, naltrexone-blocked, cross-over study. Healthy subjects received five equivalent oxycodone doses: Xtampza ER (intact or crushed), OxyContin R (intact or crushed) or immediate-release (IR) oxycodone (crushed). Blood samples were collected to assess oxycodone concentrations. Results: Crushed and intact Xtampza ER resulted in lower peak plasma concentrations compared with crushed oxycodone IR; crushed and intact Xtampza ER were bioequivalent. Crushed OxyContin exhibited a rapid increase in plasma oxycodone and was bioequivalent to crushed oxycodone IR. Conclusion: This second pharmacokinetic study demonstrated that Xtampza ER maintains its ER properties after crushing, unlike OxyContin, which failed to retain its ER properties after crushing.

Abuse-Deterrent Opioid Analgesics: A Guide for Clinicians

“…Table 1 summarizes the abuse-deterrence claims from the prescribing information for commercially available abuse-deterrent opioids [18][19][20][21][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. All abuse-deterrent opioid labels include a statement saying that abuse (by oral, intranasal and/or IV routes) is still possible.…”

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®)

“…Premarket in vitro and in vivo testing of Xtampza ER is well documented and demonstrates the difficulties in manipulating the product as well as the product's pharmacokinetic profile and human abuse potential. [7][8][9][10][11][12][13][14] Published postmarket data is limited to a recent publication comparing Xtampza ER to IR oxycodone, other ADF ER opioids, and non-ADF ER opioids which suggested that Xtampza ER has low relative abuse rates and low relative likelihood of non-oral use. 15 While these results were consistent across several data sources, additional real-world data are needed to further understand the relative risk of abuse of currently available opioid medications.…”

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza® ER (oxycodone DETERx® formulation): A review of published studies

“…17 The effects of drug manipulation on the PK profile of Xtampza ER after oral administration were evaluated in five studies (Table 1). 8,20,[22][23][24] The effects of crushing (based on the most effective crushing methods using household utensils [common household items that crush, cut, or grate by manual or mechanical means] that could be easily accessed by abusers) and chewing (one of the most common prescription opioid tampering methods 16 ) on the PK profile of Xtampza ER capsule contents were compared with the PK profile of IR oxycodone solution in one category 2 study. 20 In addition, the effects of chewing on the PK profile of Xtampza ER were compared with that of crushed IR oxycodone as part of two category 3 (human abuse potential) studies in nondependent, recreational opioid users.…”

“…23,24 Two additional category 2 studies compared the effects of crushing on the PK profile of Xtampza ER capsule contents with the PK profile of crushed IR oxycodone and crushed reformulated OxyContin. 8,22 Because food consumption may alter drug availability, FDA guidance recommends modified-release drugs be evaluated under fasted and fed conditions when characterizing bioequivalence. 25 The Xtampza ER PK profile was therefore assessed in fasted 23,24 and fed 8,20,[22][23][24] conditions in these studies, in line with FDA guidance.…”

“…8,22 Because food consumption may alter drug availability, FDA guidance recommends modified-release drugs be evaluated under fasted and fed conditions when characterizing bioequivalence. 25 The Xtampza ER PK profile was therefore assessed in fasted 23,24 and fed 8,20,[22][23][24] conditions in these studies, in line with FDA guidance.…”