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Abuse-deterrent opioid formulations: Are they a pipe dream?

  • Nathaniel Katz
Article

Abstract

The continued need for opioids to treat pain and their unavoidable link to abuse and addiction create a need for risk mitigation approaches that optimize their risk-benefit ratio. Abuse-deterrent formulations (ADFs) have emerged as a means for supporting opioid access while limiting abuse and its consequences. Several different types of ADFs have emerged including physical barriers to tampering, agonist-antagonist formulations, aversion, prodrugs, and alternative methods of administration. Each of these types has the potential to reduce specific forms of prescription opioid abuse. ADFs have the potential to reduce the public health burden of prescription opioid abuse, but they will require not only technically successful formulations, but also appropriate scientific assessment, widespread market penetration, and rational expectations of their benefits.

Keywords

Buprenorphine Naltrexone Oxycodone Methadone Maintenance Treatment Prescription Opioid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Katz NP, Adams EH, Benneyan JC, et al.: Foundations of opioid risk management. Clin J Pain 2007, 23:103–118.PubMedCrossRefGoogle Scholar
  2. 2.
    Savage S, Covington EC, Heit HA, et al.: Definitions related to the use of opioids for the treatment of pain. American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, 2007. Available at http://www.ampainsoc.org/advocacy/opioids2.htm. Accessed November 28, 2007.
  3. 3.
    Katz NP, Adams EH, Chilcoat H, et al.: Challenges in the development of prescription opioid abuse-deterrent formulations. Clin J Pain 2007, 23:648–660.PubMedCrossRefGoogle Scholar
  4. 4.
    Substance Abuse and Mental Health Services Administration: Results from the 2006 National Survey on Drug Use and Health: National Findings. (Office of Applied Studies, NSDUH Series H-32, DHHS Publication No. SMA 07-4293). Rockville, MD: Department of Health and Human Services; 2007.Google Scholar
  5. 5.
    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4 edn, text revision.Google Scholar
  6. 6.
    O’Brien CP, Volkow N, Li TK: What’s in a word? Addiction vs. dependence in DSM-V. Am J Psychiatry 2006, 163:764–765.PubMedCrossRefGoogle Scholar
  7. 7.
    Hays LR: A profile of OxyContin addiction. J Addict Dis 2004, 23:1–9.PubMedCrossRefGoogle Scholar
  8. 8.
    White AG, Birnbaum HG, Mareva MN, et al.: Direct costs of opioid abuse in an insured population in the United States. J Manag Care Pharm 2005, 11:469–479.PubMedGoogle Scholar
  9. 9.
    Compton WM, Volkow ND: Abuse of prescription drugs and the risk of addiction. Drug Alcohol Depend 2006, 83(Suppl 1):S4–S7.PubMedCrossRefGoogle Scholar
  10. 10.
    Marsch LA, Bickel WK, Badger GJ, et al.: Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans. J Pharmacol Exp Ther 2001, 299:1056–1065.PubMedGoogle Scholar
  11. 11.
    Rosenblum A, Parrino M, Schnoll SH, et al.: Prescription opioid abuse among enrollees into methadone maintenance treatment. Drug Alcohol Depend 2007, 90:64–71.PubMedCrossRefGoogle Scholar
  12. 12.
    Butler S, Budman S, Villapiano A, et al.: The NAVIPPRO System: new data on the feasibility of real-time, product specific opioid surveillance. Presented at the American Pain Society Annual Meeting. Washington, DC; May 2–7, 2007.Google Scholar
  13. 13.
    Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE: Monitoring the future national results on adolescent drug use: overview of key findings, 2006. (NIH Publication No. 07-6202). Bethesda, MD: National Institute on Drug Abuse; 2007.Google Scholar
  14. 14.
    Watson WA, Litovitz TL, Rodgers GC Jr, et al.: 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2005, 23:589–666.PubMedCrossRefGoogle Scholar
  15. 15.
    Substance Abuse and Mental Health Services Administration, Office of Applied Studies: Drug Abuse Warning Network, 2005: National estimates of drug-related emergency department visits. (DAWN Series D-29, DHHS Publication No. SMA 07-4256.) Rockville, MD: Department of Health and Human Services; 2007.Google Scholar
  16. 16.
    Passik SD, Kirsh KL, Donaghy KB, Portenoy RK: Pain and aberrant drug-related behaviors in medically ill patients with and without histories of substance abuse. Clin J Pain 2006, 22:173–181.PubMedCrossRefGoogle Scholar
  17. 17.
    Paulozzi LJ, Ryan GW: Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med 2006, 31:506–511.PubMedCrossRefGoogle Scholar
  18. 18.
    Substance Abuse and Mental Health Services Administration, Office of Applied Studies: Drug Abuse Warning Network, 2003: area profiles of drug-related mortality. (DAWN Series D-27, DHHS Publication No. SMA 05-4023.) Rockville, MD: Department of Health and Human Services; 2005.Google Scholar
  19. 19.
    Substance Abuse and Mental Health Services Administration, Office of Applied Studies: Disposition of emergency department visits for drug-related suicide attempts by adolescents: 2004. The New DAWN Report. Issue 6. Rockville, MD: Department of Health and Human Services; 2006.Google Scholar
  20. 20.
    Booth M: Opium: A History. New York: St. Martins Press; 1996.Google Scholar
  21. 21.
    Fudala PJ, Johnson RE: Development of opioid formulations with limited diversion and abuse potential. Drug Alcohol Depend 2006, 83(Suppl 1):S40–S47.PubMedCrossRefGoogle Scholar
  22. 22.
    Katz NP, Buse DC, Budman SH, et al.: Development and preliminary experience with an ease of extractability rating system for prescription opioids. Drug Dev Ind Pharm 2006, 32:727–746.PubMedCrossRefGoogle Scholar
  23. 23.
    Cone EJ: Ephemeral profiles of prescription drug and formulation tampering: evolving pseudoscience on the Internet. Drug Alcohol Depend 2006, 83(Suppl 1):S31–S39.PubMedCrossRefGoogle Scholar
  24. 24.
    Webster LR: PTI-821: sustained-release oxycodone using gel-cap technology. Expert Opin Investig Drugs 2007, 16:359–366.PubMedCrossRefGoogle Scholar
  25. 25.
    Bartholomaeus J, Arkenau E, Ashworth JB: A new technology to increase the mechanical stability of matrix tablets to prevent abuse by crushing or chewing. Presented at the College of Problems in Drug Dependency. Bethesda, MD; April 19–20, 2005.Google Scholar
  26. 26.
    Collegium Pharmaceutical: Central nervous system. Available at http://www.collegiumpharma.com/products/cns.html. Accessed November 28, 2007.
  27. 27.
    Parasrampuria DA, Schoedel KA, Schuller R, et al.: Do formulation differences alter abuse liability of methylphenidate? A placebo-controlled, randomized, double-blind, crossover study in recreational drug users. J Clin Psychopharmacol 2007, 27:459–467.PubMedCrossRefGoogle Scholar
  28. 28.
    Teter CJ, McCabe SE, LaGrange K, et al.: Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration. Pharmacotherapy 2006, 26:1501–1510.PubMedCrossRefGoogle Scholar
  29. 29.
    Lahmeyer HW, Craig RJ: Pentazocine-naloxone: another “addiction-proof” drug of abuse. Int J Addict 1987, 22:1163–1166.PubMedGoogle Scholar
  30. 30.
    Alho H, Sinclair D, Vuori E, Holopainen A: Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend 2007, 88:75–78.PubMedCrossRefGoogle Scholar
  31. 31.
    US Food and Drug Administration, Center for Drug Evaluation and Research: Subutex and Suboxone: questions and answers. Available at http://www.fda.gov/cder/drug/infopage/subutex_suboxone/subutex-qa.htm. Accessed November 28, 2007.
  32. 32.
    Katz N, Sun S, Fox L, et al.: Treatment of osteoarthritis pain with extended-release morphine sulfate plus sequestered naltrexone ASA 2007 Annual Meeting [abstract #652984]. Presented at the American Society of Anesthesiologists. San Francisco, CA; October 15, 2007.Google Scholar
  33. 33.
    Elite Pharmaceuticals Inc.: Home page. Available at www.elitepharma.com. Accessed November 28, 2007.Google Scholar
  34. 34.
    Woolf CJ, Hashmi M: Use and abuse of opioid analgesics: potential methods to prevent and deter non-medical consumption of prescription opioids. Curr Opin Investig Drugs 2004, 5:61–66.PubMedGoogle Scholar
  35. 35.
    Gershell L, Goater JJ: From the analyst’s couch: making gains in pain. Nat Rev Drug Discov 2006, 5:889–890.PubMedCrossRefGoogle Scholar
  36. 36.
    Acura Pharmaceuticals Inc.: Home page. Available at http://www.acurapharm.com. Accessed November 28, 2007.
  37. 37.
    Vyvanse [package insert]. Hampshire, UK: Shire Pharmaceuticals; 2007.Google Scholar
  38. 38.
    Rosenblum A, Parrino M, Schnoll SH, et al.: Prescription opioid abuse among enrollees into methadone maintenance treatment. Drug Alcohol Depend 2007, 90:64–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Butler SF, Benoit CM, Budman SH, et al.: Development and validation of an opioid attractiveness scale: a novel measure of the attractiveness of opioid products to potential abusers. Harm Reduct J 2006, 3:5.PubMedCrossRefGoogle Scholar
  40. 40.
    Bell J, White J, Saunders J, et al.: PROBUPHINE (buprenorphine implant) provides sustained serum buprenorphine concentrations and long-term control of withdrawal symptoms and cravings [poster]. Presented at the College on Problems of Drug Dependence 66th Annual Scientific Meeting. San Juan, Puerto Rico; June 12–17, 2004.Google Scholar
  41. 41.
    Sobel BF, Sigmon SC, Walsh SL, et al.: Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification. Drug Alcohol Depend 2004, 73:11–22.PubMedCrossRefGoogle Scholar
  42. 42.
    Katz N, Fanciullo GJ: Role of urine toxicology testing in the management of chronic opioid therapy. Clin J Pain 2002, 18(4 Suppl):S76–S82.PubMedCrossRefGoogle Scholar
  43. 43.
    Ives TJ, Chelminski PR, Hammett-Stabler CA, et al.: Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Serv Res 2006, 6:46.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Analgesic ResearchNeedhamUSA

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