Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties

Gudin, Jeffrey; Levy‐Cooperman, Naama; Kopecky, Ernest A.; Fleming, Alison B.

doi:10.1111/pme.12834

Cited by 38 publications

(59 citation statements)

References 21 publications

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“…These results were similar to previously published data on the comparative PK of Xtampza ER and OxyContin administered intact and after crushing and chewing [8,13], confirming the results from a similar previously published study [10] and establishing the consistency of the PK of Xtampza ER (Supplementary Table), further demonstrating the ability of Xtampza ER to retain its ER characteristics after manipulation, unlike OxyContin [8,10,13,14]. Similar to previously published data [10], the safety profiles of crushed and intact Xtampza ER were comparable. The reported AEs in both studies were mild to moderate in intensity, not clinically significant and were all common AEs associated with opioid administration.…”

Section: Discussionsupporting

confidence: 83%

“…Studies with Xtampza ER indicate that it retains its ER characteristics after crushing or chewing [8,10]; as a result, Xtampza ER is the first and only ER opioid formulation that does not include language in the boxed warning about potential dangers of crushing or chewing before ingestion [26]. Based on published data [8,10,13,14], including this study, crushed OxyContin results in a rapid increase in serum oxycodone concentrations and thus, a higher AQ. This fact may reveal why oral abuse after manipulation remains prevalent for hard-to-crush tablet formulations.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were recruited at a clinical research unit (Frontage, NJ, USA) similar to a previous study [10]. Subjects were either already part of the site's database and were contacted by telephone or they were recruited using studyspecific advertisements.…”

Section: Methodsmentioning

confidence: 99%

“…This second, confirmatory study was designed to replicate a previous study that compared the PK profile of Xtampza ER with the currently marketed OxyContin [10].…”

mentioning

confidence: 99%

“…Xtampza ER was designed to resist extraction and to retain its ER characteristics following tampering with commonly available utensils. Previous in vitro [8,9] and in vivo [8,10] studies have assessed the effect of manipulation of Xtampza ER, demonstrating that despite aggressive manipulation, Xtampza ER microspheres retain their ER characteristics. An added benefit of Xtampza ER is the microsphere-in-capsule design.…”

mentioning

confidence: 99%

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

Brennan¹,

Kopecky

Marseilles

et al. 2017

Pain Manag.

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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.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…This second, confirmatory study was designed to replicate a previous study that compared the PK profile of Xtampza ER with the currently marketed OxyContin [10].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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

Brennan¹,

Kopecky

Marseilles

et al. 2017

Pain Manag.

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Oral Human Abuse Potential of Oxycodone DETERx^® (Xtampza^® ER)

Kopecky

Fleming

Levy‐Cooperman³

et al. 2016

The Journal of Clinical Pharma

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Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate‐release oxycodone.

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Drug Formulation Advances in Extended-Release Medications for Pain Control

Jones

Carney

Kaye

et al. 2016

Curr Pain Headache Rep

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Prescription opioid abusers frequently tamper with opioid tablets in order to either accelerate the delivery of the euphoria-inducing agent or to alter the route of delivery, such that it may be delivered intranasally or intravenously. As one strategy to combat the opioid epidemic in the USA, drug manufacturers have begun to explore formulations which resist such tampering by abusers. Techniques to prevent tampering consist of physical barriers to crushing, chewing, and drug extraction, or aversive or antagonistic agents, incorporated within the formulation itself. Recent years have seen the development of numerous extended-release opioid agents, which are described in this review. This article provides a comprehensive summary of the pharmacology, benefits, risks, and processes behind the development of currently available extended-release opioid drugs, as well as a glimpse into promising future formulations.

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Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties

Cited by 38 publications

References 21 publications

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

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

Oral Human Abuse Potential of Oxycodone DETERx^® (Xtampza^® ER)

Drug Formulation Advances in Extended-Release Medications for Pain Control

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Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties

Cited by 38 publications

References 21 publications

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

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

Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

Drug Formulation Advances in Extended-Release Medications for Pain Control

Contact Info

Product

Resources

About

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

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

Oral Human Abuse Potential of Oxycodone DETERx^® (Xtampza^® ER)