Advances in Therapy

, Volume 31, Issue 3, pp 264–275

Tamper-Resistant Opioid Formulations in the Treatment of Acute Pain

Review

Abstract

Introduction

Pain—including acute or persistent acute pain—is a common condition that is increasingly being treated with opioids in the United States. The acute pain treatment setting may represent a key target for addressing the growing epidemic of prescription drug abuse occurring hand in hand with the rise in opioid prescribing. Balancing the needs of pain treatment with abuse prevention can be challenging for clinicians.

Methods

This article identified efforts to balance opioid abuse risks with opioid availability through the extensive experience of the author in this field. In addition, PubMed literature searches using terms such as “prescription opioid abuse”, “abuse-deterrent opioids”, and “tamper-resistant opioids”; and inspection of the bibliographies of relevant articles were used to identify relevant sources.

Results

These multifaceted efforts have included: improving assessment of patient risk for drug misuse, abuse, or diversion; funding of and encouraging referral to addiction treatment programs; access to and widespread use of prescription monitoring programs (PMPs); public knowledge of prescription opioid abuse; proper storage of opioid medications; and development of new formulations designed to resist tampering and deter abuse. This review discusses the problem of prescription opioid abuse and strategies to minimize risk within the context of acute pain treatment, and explores the potential role of tamper-resistant opioid formulations and other abuse deterrence strategies in the area of acute or persistent acute pain management.

Conclusion

In order to stem the tide of prescription opioid abuse and preserve the availability of opioids as a much needed analgesic option, a multifaceted approach that includes tamper-resistant opioid formulations—for chronic or acute pain—along with strategies such as improved patient risk assessment, funding for and referral to addiction treatment programs, greater use of PMPs, and raised awareness of prescription opioid abuse is needed.

Keywords

Acute pain Opioid abuse Opioids Pain Pain medications Tamper-resistant formulations 

Supplementary material

12325_2014_99_MOESM1_ESM.pdf (266 kb)
Supplementary material 1 (PDF 266 kb)

References

  1. 1.
    US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Health, United States, 2006. With chartbook on trends in the health of Americans. Hyattsville: National Center for Health Statistics; 2006. DHHS Publication No. 2006-1232. http://www.cdc.gov/nchs/data/hus/hus06.pdf. Accessed January 10, 2013.
  2. 2.
    Sinatra R. Causes and consequences of inadequate management of acute pain. Pain Med. 2010;11:1859–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Pletcher MJ, Kertesz SG, Kohn MA, Gonzales R. Trends in opioid prescribing by race/ethnicity for patients seeking care in US emergency departments. JAMA. 2008;299:70–8.PubMedGoogle Scholar
  4. 4.
    Manchikanti L, Helm S, Fellows B, Janata JW, Pampati V, Grider JS, et al. Opioid epidemic in the United States. Pain Physician. 2012;15:ES9–38.PubMedGoogle Scholar
  5. 5.
    Volkow ND, McLellan TA, Cotto JH, Karithanom M, Weiss SR. Characteristics of opioid prescriptions in 2009. JAMA. 2011;305:1299–301.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Prescription painkiller overdoses in the US. November, 2011. http://www.cdc.gov/VitalSigns/pdf/2011-11-vitalsigns.pdf. Accessed December 9, 2012.
  7. 7.
    Volkow ND, McLellan TA. Curtailing diversion and abuse of opioid analgesics without jeopardizing pain treatment. JAMA. 2011;305:1346–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Jones CM. Frequency of prescription pain reliever nonmedical use: 2002–2003 and 2009–2010. Arch Intern Med. 2012;172:1–2.CrossRefGoogle Scholar
  9. 9.
    Cai R, Crane E, Poneleit K, Paulozzi L. Emergency department visits involving nonmedical use of selected prescription drugs—United States, 2004–2008. MMWR Morb Mortal Wkly Rep. 2010;59:705–9.Google Scholar
  10. 10.
    Paulozzi LJ, Jones CM, Mack KA, Rudd RA. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR Morb Mortal Wkly Rep. 2011;60:1487–92.Google Scholar
  11. 11.
    Paulozzi L, Baldwin G, Franklin G, et al. CDC grand rounds: prescription drug overdoses—a US epidemic. MMWR Morb Mortal Wkly Rep. 2012;61:10–3.Google Scholar
  12. 12.
    Perrone J, Nelson LS. Medication reconciliation for controlled substances—an “ideal” prescription-drug monitoring program. N Engl J Med. 2012;366:2341–3.PubMedCrossRefGoogle Scholar
  13. 13.
    Chapman CR, Nakamura Y. A passion of the soul: an introduction to pain for consciousness researchers. Conscious Cogn. 1999;8:391–422.PubMedCrossRefGoogle Scholar
  14. 14.
    The Joint Commission on Accreditation of Healthcare Organizations, The National Pharmaceutical Council. Pain: current understanding of assessment, management and treatments. Washington, DC: The National Pharmaceutical Council; 2001. http://www.npcnow.org/system/files/research/download/Pain-Current-Understanding-of-Assessment-Management-and-Treatments.pdf. Accessed January 16, 2014.
  15. 15.
    Butler SF, Black RA, Cassidy TA, Dailey TM, Budman SH. Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm Reduct J. 2011;8:29.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Dart R. RADARS® System Sixth Annual Meeting. April 24, 2012. http://www.radars.org/Portals/1/01_DartR_RADARS_System_Annual_Meeting_2012_distribution_20120502.pdf. Accessed December 9, 2012.
  17. 17.
    Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System. RADARS® System data indicate immediate release opioids responsible for higher proportion of misuse, abuse and diversion than extended release opioids. RADARS Syst News. 2009;4:1–4.Google Scholar
  18. 18.
    US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. Rockville: Substance Abuse and Mental Health Services Administration; September 2011. NSDUH Series H-41, HHS Publication No. (SMA) 11-4658. http://oas.samhsa.gov/NSDUH/2k10NSDUH/2k10Results.pdf. Accessed January 10, 2013.
  19. 19.
    Sproule B, Brands B, Li S, Catz-Biro L. Changing patterns in opioid addiction: characterizing users of oxycodone and other opioids. Can Fam Physician. 2009;55:68–9.e5.Google Scholar
  20. 20.
    Bates C, Laciak R, Southwick A, Bishoff J. Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 2011;185:551–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Tanabe P, Paice JA, Stancati J, Fleming M. How do emergency department patients store and dispose of opioids after discharge? A pilot study. J Emerg Nurs. 2012;38:273–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Arria AM, Garnier-Dykstra LM, Caldeira KM, Vincent KB, O’Grady KE. Prescription analgesic use among young adults: adherence to physician instructions and diversion. Pain Med. 2011;12:898–903.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I—evidence assessment. Pain Physician. 2012;15:S1–66.PubMedGoogle Scholar
  24. 24.
    Governale L. Outpatient prescription opioid utilization in the U.S., years 2000–2009. Silver Spring: U.S. Food and Drug Administration; July 2010. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProductsAdvisoryCommittee/UCM220950.pdf. Accessed August 1, 2012.
  25. 25.
    Tufts Health Care Institute. The role of dentists in preventing opioid abuse. Tufts Health Care Institute Program on Opioid Risk Management. 12th Summit Meeting. Executive Summary. Boston: Tufts Health Care Institute; 2010. http://www.thci.org/opioid/mar10docs/executivesummary.pdf Accessed January 10, 2013.
  26. 26.
    Chapman CR, Fosnocht D, Donaldson GW. Resolution of acute pain following discharge from the emergency department: the acute pain trajectory. J Pain. 2012;13:235–41.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Wang CK, Myunghae HJ, Carroll I. Factors contributing to pain chronicity. Curr Pain Headache Rep. 2009;13:7–11.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Hermos JA, Young MM, Gagnon DR, Fiore LD. Characterizations of long-term oxycodone/acetaminophen prescriptions in veteran patients. Arch Intern Med. 2004;164:2361–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Webster LR, Bath B, Medve RA. Opioid formulations in development designed to curtail abuse: who is the target? Expert Opin Investig Drugs. 2009;18:255–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Mastropietro DJ, Omidian H. Current approaches in tamper-resistant and abuse-deterrent formulations. Drug Dev Ind Pharm. 2013;39:611–24.PubMedCrossRefGoogle Scholar
  31. 31.
    Hays LR. A profile of OxyContin addiction. J Addict Dis. 2004;23:1–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Med. 2005;6:432–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Oxecta™ (oxycodone HCl, USP) tablets for oral use only—CII [package insert]. Palatine: Acura Pharmaceuticals Inc.; 2013. http://labeling.pfizer.com/showlabeling.aspx?id=620. Accessed January 16, 2014.
  34. 34.
    Schoedel KA, Rolleri RL, Faulknor JY, et al. Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta) tablets in nondependent recreational opioid users. J Opioid Manag. 2012;8:315–27.PubMedCrossRefGoogle Scholar
  35. 35.
    Devarakonda K, Morton T, Giuliani M, et al. Single-dose pharmacokinetics of 1 and 2 tablets of MNK-795 controlled-release oxycodone/acetaminophen tablets (CR OC/APAP) compared with immediate-release oxycodone and acetaminophen. Presented at: PAINWeek; September 4–7, 2013; Las Vegas, NV. Poster 19.Google Scholar
  36. 36.
    Mallinckrodt Pharmaceuticals Announces Positive Phase 3 Efficacy Results for MNK-795, an Extended-Release Oxycodone/Acetaminophen Combination [press release]. Sept. 5, 2013. Las Vegas: Mallinckrodt Pharmaceuticals. http://news.mallinckrodt.com/press-release/company/mallinckrodt-pharmaceuticals-announces-positive-phase-3-efficacy-results-mnk-7. Accessed January 14, 2014.
  37. 37.
    Singla N, Barrett T, Sisk L, Kostenbader K, Young J, Giuliani M. A randomized, double-blind, placebo-controlled study of the efficacy and safety of MNK-795, a dual-layer, biphasic, IR and ER combination analgesic for acute pain. Curr Med Res Opin. 2014. (Epub ahead of print).Google Scholar
  38. 38.
    Morton T, Kostenbader K, Montgomery J, et al. Comparison of subjective drug effects of orally administered MNK-795 controlled-release oxycodone/acetaminophen tablets (CR OC/APAP) vs immediate-release oxycodone/acetaminophen tablets in recreational users of prescription opioids. Presented at: PAINWeek; September 4–7, 2013; Las Vegas, NV. Poster 69.Google Scholar
  39. 39.
    Pande P, Hines JW, Brogan P. Tamper-resistant properties of once-daily hydromorphone ER (OROS hydromorphone ER). Presented at: American Pain Society 30th Annual Scientific Meeting; May 19–21, 2011; Austin, TX. Poster 331.Google Scholar
  40. 40.
    Perrino PJ, Colucci SV, Apseloff G, Harris SC. Pharmacokinetics, tolerability, and safety of intranasal administration of reformulated OxyContin(®) tablets compared with original OxyContin (®) tablets in healthy adults. Clin Drug Investig. 2013;33:441–9.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Benedek IH, Jobes J, Xiang Q, Fiske WD. Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone extended release. Drug Des Devel Ther. 2011;5:455–63.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Szalavitz M. Abuse-proof OxyContin pushes addicts to heroin and other opioids, survey finds. Time Web site. July 12, 2012. http://healthland.time.com/2012/07/12/new-abuse-proof-oxycontin-formula-pushed-addicts-to-heroin-and-other-opioids-survey-finds/. Accessed January 10, 2013.
  43. 43.
    Leinwand Leger D. Opana abuse in USA overtakes OxyContin. USA Today Web site. July 10, 2012. http://usatoday30.usatoday.com/news/nation/story/2012-07-10/opana-painkiller-addiction/56137086/1. Accessed January 10, 2013.
  44. 44.
    Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of OxyContin. N Engl J Med. 2012;367:187–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Passik SD, Kirsh KL. The interface between pain and drug abuse and the evolution of strategies to optimize pain management while minimizing drug abuse. Exp Clin Psychopharmacol. 2008;16:400–4.PubMedCrossRefGoogle Scholar
  46. 46.
    Chou R, Fanciullo GJ, Fine PG, Miaskowski C, Passik SD, Portenoy RK. Opioids for chronic noncancer pain: prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain. 2009;10:131–46.PubMedCrossRefGoogle Scholar
  47. 47.
    Reisfield GM, Salazar E, Bertholf RL. Rational use and interpretation of urine drug testing in chronic opioid therapy. Ann Clin Lab Sci. 2007;37:301–14.PubMedGoogle Scholar
  48. 48.
    Center for Lawful Access and Abuse Deterrence. National prescription drug abuse prevention strategy: 2011–2012 update. Arlington, VA: Center for Lawful Access and Abuse Deterrence; 2011. http://www.claad.org/downloads/CLAAD_Strategy2011_v3.pdf. Accessed January 14, 2013.
  49. 49.
    Passik SD, Kirsh KL. Addictions in pain clinics and pain treatment. Ann N Y Acad Sci. 2011;1216:138–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Cordy C, Kelly P. Patterns of prescribing—the Rhode Island prescription monitoring program. R I Med J. 2013;96:36–7.Google Scholar
  51. 51.
    Reifler LM, Droz D, Bailey JE, et al. Do prescription monitoring programs impact state trends in opioid abuse/misuse? Pain Med. 2012;13:434–42.PubMedCrossRefGoogle Scholar
  52. 52.
    United States General Accounting Office. Prescription drugs: state monitoring programs provide useful tool to reduce diversion. May 2002. GAO-02-634. http://www.gao.gov/assets/240/234687.pdf. Accessed January 16, 2014.
  53. 53.
    Worley J. Prescription drug monitoring programs, a response to doctor shopping: purpose, effectiveness, and directions for future research. Issues Ment Health Nurs. 2012;33:319–28.PubMedCrossRefGoogle Scholar
  54. 54.
    Passik SD, Kirsh KL, Casper D. Addiction-related assessment tools and pain management: instruments for screening, treatment planning, and monitoring compliance. Pain Med. 2008;9:S145–66.CrossRefGoogle Scholar
  55. 55.
    Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2—guidance. Pain Physician. 2012;15:S67–116.PubMedGoogle Scholar
  56. 56.
    Inciardi JA, Surratt HL, Cicero TJ, Beard RA. Prescription opioid abuse and diversion in an urban community: the results of an ultrarapid assessment. Pain Med. 2009;10:537–48.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Executive Office of the President of the United States. Epidemic: responding to America’s prescription drug abuse crisis. Washington, DC: Executive Office of the President of the United States; 2011. http://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/rx_abuse_plan.pdf. Accessed January 14, 2013.
  58. 58.
    US Department of Health and Human Services, US Food and Drug Administration. FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. Silver Spring: US Food and Drug Administration; July 2012. http://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm277916.pdf. Accessed January 14, 2013.
  59. 59.
    Nelson LS, Perrone J. Curbing the opioid epidemic in the United States: the risk evaluation and mitigation strategy (REMS). JAMA. 2012;308:457–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2014

Authors and Affiliations

  1. 1.Millennium Laboratories, Inc. and Millennium Research InstituteSan DiegoUSA

Personalised recommendations