Open Access Open Access  Restricted Access Subscription or Fee Access

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

Jeffrey Gudin, MD

Abstract


Opioids can be an effective treatment option for appropriate patients with chronic pain for whom nonpharmacological or nonopioid treatment does not provide adequate pain relief. However, extended-release (ER) opioid formulations, because of their high drug content, are attractive options for nonmedical use and abuse. Xtampza® ER (oxycodone DETERx®) capsules, an ER abuse-deterrent formulation (ADF), contain microspheres that combine oxycodone with inactive ingredients to increase the difficulty of tampering with the ER mechanism. The aim of this article is to review five previously published studies highlighting the impact of physical manipulation (ie, crushing and chewing) on the pharmacokinetic (PK) properties of orally administered Xtampza ER compared with immediate-release (IR) oxycodone and/or reformulated OxyContin® (the first approved oxycodone ER ADF). Across five studies, manipulated (crushed or chewed) Xtampza ER retained an ER PK profile similar to that of intact Xtampza ER, with respect to maximum plasma concentration (Cmax) and time to Cmax. Additionally, bioequivalence was established between manipulated and intact Xtampza ER, based on Cmax and area under the concentration-time curve values in healthy volunteers and nondependent recreational opioid users. In contrast, crushed OxyContin failed to retain the ER PK profile of intact OxyContin and was bioequivalent to IR oxycodone, based on Cmax in healthy volunteers. The retention of ER PK properties when capsule contents are physically manipulated before oral administration suggests Xtampza ER has lower potential to be manipulated for oral abuse when compared with IR oxycodone or OxyContin.


Keywords


abuse, abuse-deterrent, extended-release, Oxycodone DETERx, OxyContin, opioid analgesics, tamper, Xtampza

Full Text:

PDF

References


Institute of Medicine Committee on Advancing Pain Research Care and Education: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: The National Academies Press; 2011.

Furlan AD, Sandoval JA, Mailis-Gagnon A, et al.: Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. CMAJ. 2006; 174(11): 1589-1594.

Kalso E, Edwards JE, Moore RA, et al.: Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004; 112(3): 372-380.

Brennan MJ: Update on prescription extended-release opioids and appropriate patient selection. J Multidiscip Healthcare. 2013; 6: 265-280.

Graziottin A, Gardner-Nix J, Stumpf M, et al.: Opioids: how to improve compliance and adherence. Pain Pract. 2011; 11(6): 574-581.

Webster L: Update on abuse-resistant and abuse-deterrent approaches to opioid formulations. Pain Med. 2009; 10(Suppl 2): S124-S133.

Gudin J: Oxycodone DETERx®: A novel abuse-deterrent, extended-release analgesic option for the treatment of patients with chronic pain. Pain Ther. 2016; 5(2): 171-186.

Gudin J, Levy-Cooperman N, Kopecky EA, et al.: Comparing the effect of tampering on the oral pharmacokinetic profiles of two extended-release oxycodone formulations with abuse-deterrent properties. Pain Med. 2015; 16(11): 2142-2151.

Substance Abuse and Mental Health Services Administration. Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. Rockville, Maryland: Substance Abuse and Mental Health Services Administration; 2013. HHS Publication No. (SMA) 13-4760, DAWN Series D-39.

Scholl L, Seth P, Kariisa M, et al.: Drug and opioid-involved overdose deaths-United States, 2013-2017. MMWR Morb Mortal Wkly Rep. 2018; 67(5152): 1419-1427.

Loeser KC, Rodriguez R: Regulatory and evidence-based considerations for abuse-deterrent opioids. Am J Health Syst Pharm. 2019; 76(2): 114-118.

Pergolizzi JV, Jr, Raffa RB, Taylor R, Jr, et al.: Abuse-deterrent opioids: An update on current approaches and considerations. Curr Med Res Opin. 2018; 34(4): 711-723.

Cicero TJ, Ellis MS: Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: Lessons learned from OxyContin. JAMA Psychiatry. 2015; 72(5): 424-430.

Coplan PM, Chilcoat HD, Butler SF, et al.: The effect of an abuse-deterrent opioid formulation (OxyContin) on opioid abuse-related outcomes in the postmarketing setting. Clin Pharmacol Ther. 2016; 100(3): 275-286.

McNaughton EC, Coplan PM, Black RA, et al.: Monitoring of internet forums to evaluate reactions to the introduction of reformulated OxyContin to deter abuse. J Med Internet Res. 2014; 16(5): e119.

Butler SF, Black RA, Fleming AB: Relative abuse of crush-resistant prescription opioid tablets via alternative oral modes of administration. Pain Med. 2018; 19: 1613-1627.

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Abuse-Deterrent Opioids--Evaluation and Labeling: Guidance for Industry. Silver Spring, Maryland: U.S. Food and Drug Administration; 2015.

Fleming AB, Scungio TA, Grima MP, et al.: In vitro assessment of the potential for abuse via the intravenous route of oxycodone DETERx® microspheres. J Opioid Manag. 2016; 12(1): 57-65.

Patheon Pharmaceuticals: Xtampza® ER (oxycodone) extended-release capsules, for oral use, CII [package insert]. Cincinnati, Ohio: Patheon Pharmaceuticals; 2018.

Kopecky EA, Fleming AB, Noonan PK, et al.: Impact of physical manipulation on in vitro and in vivo release profiles of Oxycodone DETERx®: An extended-release, abuse-deterrent formulation. J Opioid Manag. 2014; 10(4): 233-246.

Raffa RB, Pergolizzi JV, Jr: Opioid formulations designed to resist/deter abuse. Drugs. 2010; 70(13): 1657-1675.

Brennan MJ, Kopecky EA, Marseilles A, et al.: The comparative pharmacokinetics of physical manipulation by crushing of Xtampza® ER compared with OxyContin®. Pain Manag. 2017; 7(6): 461-472.

Kopecky EA, Fleming AB, Levy-Cooperman N, et al.: Oral human abuse potential of oxycodone DETERx® (Xtampza® ER). J Clin Pharmacol. 2017; 57(4): 500-512.

Meske D, Kopecky EA, Passik S, et al.: Evaluation of the oral human abuse potential of oxycodone DETERx® formulation (Xtampza® ER). J Opioid Manag. 2018; 14(5): 359-372.

US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research: Food-Effect Bioavailability and Fed Bioequivalence Studies. Rockville, Maryland: Food and Drug Administration; 2002.

Benziger DP, Kaiko RF, Miotto JB, et al.: Differential effects of food on the bioavailability of controlled-release oxycodone tablets and immediate-release oxycodone solution. Pharm Sci. 1996; 85(4): 407-410.

Webster J, Schenk S, Harper D: The differential role of DA and 5-HT in the discriminative stimulus properties of high vs. low doses of ± 3,4-methylenedioxymethamphetamine. Drug Alcohol Dependence. 2015; 156: e183-e245.

Gasior M, Bond M, Malamut R: Routes of abuse of prescription opioid analgesics: A review and assessment of the potential impact of abuse-deterrent formulations. Postgrad Med. 2016; 128(1): 85-96.

Pergolizzi JV, Jr, Taylor R, Jr, Nalamachu S, et al.: Challenges of treating patients with chronic pain with dysphagia (CPD): Physician and patient perspectives. Curr Med Res Opin. 2014; 30(2): 191-202.

Butler SF, Cassidy TA, Chilcoat H, et al.: Abuse rates and routes of administration of reformulated extended-release oxycodone: Initial findings from a sentinel surveillance sample of individuals assessed for substance abuse treatment. J Pain. 2013; 14(4): 351-358.

Purdue Pharma L.P.: OxyContin® (oxycodone hydrochloride) extended release tablets, for oral use, CII [package insert]. Stamford, Connecticut: Purdue Pharma L.P.; 2013.

Carter LP, Griffiths RR: Principles of laboratory assessment of drug abuse liability and implications for clinical development. Drug Alcohol Depend. 2009; 105(Suppl 1): S14-S25.

Webster LR, Kopecky EA, Smith MD, et al.: A randomized, double-blind, double-dummy study to evaluate the intranasal human abuse potential and pharmacokinetics of a novel extended-release abuse-deterrent formulation of oxycodone. Pain Med. 2016; 17(6): 1112-1130.

McCarberg BH, Kopecky EA, O'Connor M, et al.: An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: Alternative modes of administration to facilitate pain management in patients with dysphagia. Curr Med Res Opin. 2016; 32(12): 1975-1982.

Katz N, Kopecky EA, O'Connor M, et al.: A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain. Pain. 2015; 156(12): 2458-2467.




DOI: https://doi.org/10.5055/jom.2020.0559

Refbacks

  • There are currently no refbacks.