Prescription Opioid Misuse: Effective Methods for Reducing the Epidemic

Center for Disease Control and Prevetion (CDC). Vital signs: overdoses of prescription opioid pain relievers—United States, 1999-2008. MMWR. 2011;60:1487–92. Center for Disease Control and Prevetion (CDC). Emergency department visits involving nonmedical use of selected prescription drugs—United States, 2004-2008. MMWR. 2010;59:705–9. http://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabsPDFWHTML2013/Web/PDFW/NSDUH-DetTabsSect1peTabs11to18-2013.pdf. [cited December, 2014]; Available from:. Zosel A, Bartelson BB, Bailey E, Lowenstein S, Dart R. Characterization of adolescent prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-related Surveillance (RADARS®) System. J Am Acad Child Adolesc Psychiatry. 2013;52:196–204.e2. Brandt SA, Taverna EC, Hallock RM. A survey of nonmedical use of tranquilizers, stimulants, and pain relievers among college students: patterns of use among users and factors related to abstinence in non-users. Drug Alcohol Depend. 2014;143:272–6. Schepis TS, Krishnan-Sarin S. Sources of prescriptions for misuse by adolescents: differences in sex, ethnicity, and severity of misuse in a population-based study. J Am Acad Child Adolesc Psychiatry. 2009;48:828–36. Shei A, Rice JB, Kirson NY, Bodnar K, Birnbaum HG, Holly P, Ben-Joseph R. Sources of prescription opioids among diagnosed opioid abusers. Curr Med Res Opin. Published online: February 24, 2015. doi:10.1185/03007995.2015.1016607. McCabe SE, West BT, Boyd CJ. Leftover prescription opioids and nonmedical use among high school seniors: a multi-cohort national study. J Adolesc Health. 2013;52:480–5. 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. This article compiles data on the abuse risk and routes of administration of 11 commonly prescribed opioid formulations, including hydrocodone, IR and ER oxycodone, methadone, IR and ER morphine, hydromorphone, IR and ER fentanyl, IR and ER oxymorphone. It specifically examined the adjusted risk of each substance based upon their prescription volume. The authors' findings speak to the abuse potential for these compounds in order to facilitate specific approaches to address their abuse. Butler SF, Budman SH, Licari A, Cassidy TA, Lioy K, Dickinson J, et al. National addictions vigilance intervention and prevention program (NAVIPPRO): a real-time, product-specific, public health surveillance system for monitoring prescription drug abuse. Pharmacoepidemiol Drug Saf. 2008;17:1142–54. Hays LR. A profile of OxyContin addiction. J Addict Dis. 2004;23:1–9. Katz N, Dart RC, Bailey E, Trudeau J, Osgood E, Paillard F. Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions. Am J Drug Alcohol Abuse. 2011;37:205–17. Butler SF, Black RA, Serrano JM, Wood ME, Budman SH. Characteristics of prescription opioid abusers in treatment: prescription opioid use history, age, use patterns, and functional severity. J Opioid Manag. 2009;6:239–41. Young AM, Havens JR. Transition from first illicit drug use to first injection drug use among rural Appalachian drug users: a cross-sectional comparison and retrospective survival analysis. Addiction. 2012;107:587–96. Van Zee A. The promotion and marketing of Oxycontin: commercial triumph, public health tragedy. Am J Public Health. 2009;99:221–7. Cone EJ, Giordano J, Weingarten B. An iterative model for in vitro laboratory assessment of tamper deterrent formulations. Drug Alcohol Depend. 2013;131:100–5. Sellers EM, Perrino PJ, Colucci SV, Harris SC. Attractiveness of reformulated OxyContin® tablets: assessing comparative preferences and tampering potential. J Psychopharmacol. 2013;27:808–16. 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. Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of OxyContin. N Engl J Med. 2012;367:187–9. This is an important article that raised the concern of replacement of OxyContin by other opioids and heroin. It also mentions the importance of non-pharmacological strategies for reducing prescription opioid epidemic. Butler SF, Cassidy TA, Chilcoat H, Black RA, Landau C, Budman SH, 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;14:351–8. Havens JR, Leukefeld CG, DeVeaugh-Geiss AM, Coplan P, Chilcoat HD. The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers. Drug Alcohol Depend. 2014;139:9–17. Severtson SG, Bartelson BB, Davis JM, Munoz A, Schneider MF, Chilcoat H, et al. Reduced abuse, therapeutic errors, and diversion following reformulation of extended-release oxycodone in 2010. J Pain. 2013;14:1122–30. Coplan PM, Kale H, Sandstrom L, Landau C, Chilcoat HD. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22:1274–82. Sessler NE, Downing JM, Kale H, Chilcoat HD, Baumgartner TF, Coplan PM. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation. Pharmacoepidemiol Drug Saf. 2014;23:1238–46. Bartholomaeus JH, Arkenau-Maric E, Galia E. Opioid extended-release tablets with improved tamper-resistant properties. Expert Opin Drug Deliv. 2012;9:879–91. Vosburg SK, Jones JD, Manubay JM, Ashworth JB, Benedek IH, Comer SD. Assessment of a formulation designed to be crush-resistant in prescription opioid abusers. Drug Alcohol Depend. 2012;126:206–15. Center for Disease Control and Prevetion (CDC). Thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse--Tennessee, 2012. MMWR. 2013;62:1–4. Kapila A, Chhabra L, Chaubey VK, Summers J. Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users. BMJ Case Rep 2014; 2014. Ambruzs JM, Serrell PB, Rahim N, Larsen CP. Thrombotic microangiopathy and acute kidney injury associated with intravenous abuse of an oral extended-release formulation of oxymorphone hydrochloride: kidney biopsy findings and report of 3 cases. Am J Kidney Dis. 2014;63:1022–6. Vosburg SK, Jones JD, Manubay JM, Ashworth JB, Shapiro DY, Comer SD. A comparison among tapentadol tamper-resistant formulations (TRF) and OxyContin® (non-TRF) in prescription opioid abusers. Addiction. 2013;108:1095–106. Hanna M. Thipphawong J,118 Study Group. A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain. BMC Palliat Care. 2008;7:17. Hanna M, Tuca A, Thipphawong J. An open-label, 1-year extension of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain. BMC Palliat Care. 2009;8:14. Gardner-Nix J, Mercadante S. The role of OROS hydromorphone in the management of cancer pain. Pain Pract. 2010;10:72–7. Palangio M, Northfelt DW, Portenoy RK, Brookoff D, Doyle Jr RT, Dornseif BE, et al. Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. J Pain Symptom Manage. 2002;23:355–68. Moorman-Li R, Motycka CA, Inge LD, Congdon JM, Hobson S, Pokropski B. A review of abuse-deterrent opioids for chronic nonmalignant pain. P T. 2012;37:412–8. Raffa RB, Pergolizzi Jr JV. Opioid formulations designed to resist/deter abuse. Drugs. 2010;70:1657–75. Setnik B, Roland CL, Cleveland JM, Webster L. The abuse potential of Remoxy®, an extended-release formulation of oxycodone, compared with immediate- and extended-release oxycodone. Pain Med. 2011;12:618–31. Butler SF, Black R, Grimes Serrano JM, Folensbee L, Chang A, Katz N. Estimating attractiveness for abuse of a not-yet-marketed "abuse-deterrent" prescription opioid formulation. Pain Med. 2010;11:81–91. FDA Complete Response Letter Received for Remoxy. Jun 24, 2011. Available at: http://www.drugs.com/nda/remoxy_110624.html. Accessed January 8, 2015. Xartemis XR receives FDA approval: May reduce opioid abuse. March 28, 2014. Available at: http://formularyjournal.modernmedicine.com/formulary-journal/content/tags/acetaminophen/xartemis-xr-receives-fda-approval-may-reduce-opioid-abu. Accessed January 8, 2015. Morton T, Kostenbader K, Montgomery J, Devarakonda K, Barrett T, Webster L. Comparison of subjective effects of extended-release versus immediate-release oxycodone/acetaminophen tablets in healthy nondependent recreational users of prescription opioids: a randomized trial. Postgrad Med. 2014;126:20–32. Singla N, A randomized, double-blind, placebo-controlled, Phase 3 study of the safety and analgesic efficacy of MNK-795 controlled-release oxycodone/acetaminophen tablets (CR OC/APAP) in an acute pain model. Oral poster presentation at Pain Week 2013. September 4-7, 2013. Available at: http://www.lotuscr.com/lotus-pdf/Mallinckrodt-MNK795-PainWeek2013-OralPresentation_101.pdf. Egalet Product Pipeline. 2015. Available at: http://www.egalet.com/products-and-pipeline/pipeline/. Accessed January 8, 2015. Darwish M, Yang R, Tracewell W, Robertson Jr P, Bond M. Single- and multiple-dose pharmacokinetics of a hydrochloride bitartrate extended-release tablet formulated with abuse-deterrence technology in healthy, naltrexone-blocked volunteers. Clin Ther. 2014. doi:10.1016/j.clinthera.2014.11.014. Darwish M, Bond M, Tracewell W, Robertson Jr P, Yang R. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects. Clin Drug Investig. 2015;35:13–22. Buer LM, Havens JR, Leukefeld C. Does the new formulation of OxyContin(R) deter misuse? A qualitative analysis. Subst Use Misuse. 2014;49:770–4. Cassidy TA, DasMahapatra P, Black RA, Wieman MS, Butler SF. Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation. Pain Med. 2014;15:440–51. Daniels SE, Spivey R, Golf M, Clark FJ, Robson M, Diamond EL, Zimmerman JC, Singla S. Acurox® (Oxycodone HCl/niacin) tablets for the treatment of acute, moderate to severe pain following bunionectomy surgery in adult patients. Poster presented at American Pain Society Annual Meeting. May 7-9, 2009. Available at: http://www.lotuscr.com/lotus-pdf/Acura-Acurox-APS2009-Poster.pdf. Accessed: January 8, 2015. Feuerstein A. Pfizer, Acura Painkiller Approved by FDA. June 20, 2011. Available at: http://www.thestreet.com/story/11157620/1/pfizer-acura-painkiller-approved-by-fda.html. Accessed: January 8, 2015. Leibowitz MT, Zamora CA, Brzeczko AW, Stark JG. A single-dose, 3-way crossover pharmacokinetic comparison between immediate-release oxycodone hydrochloride with aversion technology (IRO-A, Oxecta), IRO-a with niacin, and oxycodone hydrochloride (Roxicodone) in healthy adults under fasting conditions. Am J Ther. 2014;21:99–105. Schoedel KA, Rolleri RL, Faulknor JY, Pixton GC, Chen N, Bass A, et al. Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (OxectaTM) tablets in nondependent recreational opioid users. J Opioid Manag. 2012;8:315–27. Acuracet tablets. Acura. Available at: http://acurapharm.com/products/acuracet-tablets/. Accessed: January 8, 2015. Physician Prescribing Information: EMBEDA - morphine sulfate and naltrexone hydrochloride capsule, extended release. Pfizer Laboratories Div. Pfizer Inc. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=694. Accessed: January 9, 2015. Ruan X, Chen T, Gudin J, Couch JP, Chiravuri S. Acute opioid withdrawal precipitated by ingestion of crushed Embeda (morphine extended release with sequestered naltrexone): case report and the focused review of the literature. J Opioid Manag. 2010;6:300–3. Setnik B, Roland CL, Goli V, Sommerville K, Webster L. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients. J Opioid Manag. 2013;9:139–50. Webster LR, Johnson FK, Stauffer J, Setnik B, Ciric S. Impact of intravenous naltrexone on intravenous morphine-induced high, drug liking, and euphoric effects in experienced, nondependent male opioid users. Drugs R&D. 2011;11:259–75. FDA approves abuse deterrent labeling for EMBEDA® (morphine sulfate and naltrexone hydrochloride) extended-release (ER) capsules CII. Pfizer. Available at: http://www.pfizer.com/news/press-release/press-release-detail/fda_approves_abuse_deterrent_labeling_for_embeda_morphine_sulfate_and_naltrexone_hydrochloride_extended_release_er_capsules_cii. Accessed: January 9, 2015. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2:CD002207. This Cochrane review evaluated 31 randomized controlled trials on the efficacy of buprenorphine in treating opioid addiction, compared to methadone and placebo. It is a thorough review and critical evaluation on this topic. Chiang CN, Hawks RL. Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug Alcohol Depend. 2003;70:S39–47. Middleton LS, Nuzzo PA, Lofwall MR, Moody DE, Walsh SL. The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers. Addiction. 2011;106:1460–73. Fudala PJ, Yu E, Macfadden W, Boardman C, Chiang CN. Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts. Drug Alcohol Depend. 1998;50:1–8. Preston KL, Bigelow GE, Liebson IA. Buprenorphine and naloxone alone and in combination in opioid-dependent humans. Psychopharmacology (Berl). 1988;94:484–90. Alho H, Sinclair D, Vuori E, Holopainen A. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007;88:75–8. Furst RT. Suboxone misuse along the opiate maintenance treatment pathway. J Addict Dis. 2013;32:53–67. Smith MY, Bailey JE, Woody GE, Kleber HD. Abuse of buprenorphine in the United States: 2003–2005. J Addict Dis. 2007;26:107–11. Soyka M. Buprenorphine and buprenorphine/naloxone intoxication in children—how strong is the risk? Curr Drug Abuse Rev. 2013;6:63–70. Das NG, Das SK. Development of mucoadhesive dosage forms of buprenorphine for sublingual drug delivery. Drug Deliv. 2004;11:89–95. Strain EC, Harrison JA, Bigelow GE. Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble films. Clin Pharmacol Ther. 2011;89:443–9. Lintzeris N, Leung SY, Dunlop AJ, Larance B, White N, Rivas GR, et al. A randomised controlled trial of sublingual buprenorphine-naloxone film versus tablets in the management of opioid dependence. Drug Alcohol Depend. 2013;131:119–26. Sobel BF, Sigmon SC, Walsh SL, Johnson RE, Liebson IA, Nuwayser ES, et al. Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification. Drug Alcohol Depend. 2004;73:11–22. Sigmon SC, Wong CJ, Chausmer AL, Liebson IA, Bigelow GE. Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Addiction. 2004;99:1439–49. Ling W, Mooney L, Zhao M, Nielsen S, Torrington M, Miotto K. Selective review and commentary on emerging pharmacotherapies for opioid addiction. Subst Abuse Rehabil. 2011;2:181–8. White J, Bell J, Saunders JB, Williamson P, Makowska M, Farquharson A, et al. Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. Drug Alcohol Depend. 2009;103:37–43. Ling W. Buprenorphine implant for opioid addiction. Pain Manag. 2012;2:345–50. Rosenthal RN, Ling W, Casadonte P, Vocci F, Bailey GL, Kampman K, et al. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013;108:2141–9. Johnson H, Paulozzi L, Porucznik C, Mack K, Herter B. Decline in drug overdose deaths after state policy changes—Florida, 2010-2012. MMWR. 2014;63:569–74. Surratt HL, O'Grady C, Kurtz SP, Stivers Y, Cicero TJ, Dart RC, et al. Reductions in prescription opioid diversion following recent legislative interventions in Florida. Pharmacoepidemiol Drug Saf. 2014;23:314–20. Curtis LH, Stoddard J, Radeva JI, Hutchison S, Dans PE, Wright A, et al. Geographic variation in the prescription of schedule II opioid analgesics among outpatients in the United States. Health Serv Res. 2006;41:837–55. Reifler LM, Droz D, Bailey JE, Schnoll SH, Fant R, Dart RC, et al. Do prescription monitoring programs impact state trends in opioid abuse/misuse? Pain Med. 2012;13:434–42. Wang J, Christo PJ. The influence of prescription monitoring programs on chronic pain management. Pain Physician. 2009;12:507–15. Fischer B, Bibby M, Bouchard M. The global diversion of pharmaceutical drugsnon-medical use and diversion of psychotropic prescription drugs in North America: a review of sourcing routes and control measures. Addiction. 2010;105:2062–70. McCabe SE, West BT, Boyd CJ. Leftover prescription opioids and nonmedical use among high school seniors: a multi-cohort national study. J Adolesc Health. 2013;52:480–5. 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. Fain KM, Alexander GC. Disposing of medicines safely. Am J Public Health. 2014;104:e2–3. Manchikanti L, Manchukonda R, Damron KS, Brandon D, McManus CD, Cash K. Does adherence monitoring reduce controlled substance abuse in chronic pain patients? Pain Physician. 2006;9:57–60. Manchikanti L, Manchukonda R, Pampati V, Damron KS, Brandon DE, Cash KA, et al. Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids? Pain Physician. 2006;9:123–9. Bujold E, Huff J, Staton EW, Pace WD. Improving use of narcotics for nonmalignant chronic pain: a lesson from Community Care of North Carolina. J Opioid Manag. 2012;8:363–7. Gatchel RJ, Okifuji A. Evidence-based scientific data documenting the treatment effectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain. 2006;7:779–93. Sletten CD, Kurklinsky S, Chinburapa V, Ghazi S. Economic analysis of a comprehensive pain rehabilitation program: a collaboration between Florida Blue and Mayo Clinic Florida. Pain Med. Published online: February 3, 2015. DOI: 10.1111/pme.12679.