Joseph V. PERGOLIZZI, Gül TALU KÖKNEL, Gianpetrio ZMPONGA, Serdar ERDİNE, Robert TAYLOR, Burak AYAN, Robert BRAFFA

Maximizing value in opioid utilization: Is oxycodone immediate release a good option for pain management?

Ağrı tedavisine modern yaklaşım sürecin her yönüyle optimal düzeye getirilmesinden geçer. Bu yaklaşım farmakolojik olan ve ol- mayan yöntemlerin kullanılmasını, hastanın karakteristik özelliklerinin göz önüne alınmasını, ağrı fzyolojisinin analjeziğin etki mekanizması (farmakodinamisi), etkisinin başlama anı ve süresi (farmakokinetiği) ile uygun biçimde eşleştirilmesini içerir. Her- hangi bir tek ajan veya formülasyon hastaların tümünün her gereksinmesini karşılayamaz. Aspirin ve diğer steroit yapısında ol- mayan antienfamatuvar ilaçlar (NSAİİler) infamatuvar ağrı, asetaminofen haff ağrıda etkilidir. Özel ilaçlar migren baş ağrısı gibi spesifk ağrılarda etkilidir. Opioidler şiddetli ağrıda standart seçenek olmayı sürdürmektedir. Genellikle güvenli ve etkili seçenek olmalarına rağmen opioidler dozla sınırlı advers etkilere neden olabildikleri gibi, kötüye kullanım potansiyele de sahiptirler. O halde ağrı tedavisinin amacı en düşük opioid dozuyla ağrının maksimum düzeyde yok edilmesini sağlamaktır. Bu analjezik kullanımına ilişkin yaklaşım temelinde, dozun ağrı düzeyiyle zamansal eşleşmesini maksimize edebilen ve ilaca total maruziyet seviyesini düşüren bilinen opioid oksikodonun hızlı salımlı (IR) ve hemen titre edilen oral formülasyonu geliştirilmiştir. Bu makale ağrı tedavisinde hızlı salımlı oral formülasyon (IR) seçeneğini göz önüne almaktadır.

Opioid kullanımının değerini maksimize etmek: Hızlı salımlı oksikodon ağrı tedavisinde iyi bir seçenek midir?Gianpetrio

Te modern approach to the management of pain involves optimizing all aspects of the process. Tis includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiol- ogy of the pain with the analgesics mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfes all of the requirements for all patients. Aspirin and other non-steroidal anti-infammatory drugs (NDAIDs) are efective options for infammatory pain and, as is acetaminophen, for mild pain. Specialized agents are helpful for particular pains, such as for migraine headache. Opioids remain the standard op- tion for severe pain. Although they are generally a safe and efective option, opioids can produce dose-limiting adverse efects and have abuse potential. Te goal of pain therapy is thus to achieve the maximum pain relief with the least amount of opioid exposure. Against this background of measured approach to the use of analgesics, an immediate release (IR) oral formulation of the established opioid oxycodone has been developed to provide rapid onset of action and rate of titration, both of which could maximize temporal matching of dose with pain level and reduce total exposure to drug. Tis article considers the option of an immediate release (IR) oral formulation for the management of pain.

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1. World Health Organization. WHOs pain ladder for adults. 1988; http://www.who.int/cancer/palliative/painladder/ en/. Accessed 7 May, 2013.
2. Kalso E. Oxycodone. J Pain Symptom Manage 2005;29(5 Suppl):47-56.
3. Smith H. Introduction to Opioids. New York: Oxford Univer- sity Press; 2013.
4. Stamer UM, Zhang L, Book M, Lehmann LE, Stuber F, Muss- hof F. CYP2D6 genotype dependent oxycodone metabo- lism in postoperative patients. PLoS One 2013;8(3):60239.
5. Smith H, Bruckenthal P. Implications of opioid analge- sia for medically complicated patients. Drugs Aging 2010;27(5):417-33.
6. Pergolizzi J, Böger RH, Budd K, Dahan A, Erdine S, Hans G, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Ex- pert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxyco- done). Pain Pract 2008;8(4):287-313.
7. Chan S, Edwards SR, Wyse BD, Smith MT. Sex diferences in the pharmacokinetics, oxidative metabolism and oral bio- availability of oxycodone in the Sprague-Dawley rat. Clin Exp Pharmacol Physiol 2008;35(3):295-302.
8. Han H, Kass PH, Wilsey BL, Li CS. Age, gender, and earlier opioid requirement associations with the rate of dose es- calation in long-term opioid therapy. J Opioid Manag 2013;9(2):129-38.
9. Zacny JP. Morphine responses in humans: a retrospec- tive analysis of sex diferences. Drug Alcohol Depend 2001;63(1):23-8.
10. Christo PJ, Grabow TS, Raja SN. Opioid efectiveness, addic- tion, and depression in chronic pain. Adv Psychosom Med 2004;25:123-37.
11. Chou R. 2009 Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: what are the key messages for clinical practice? Pol Arch Med Wewn 2009;119(7-8):469-77.
12. Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol 2012;13(2):58-68.
13. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the manage- ment of hip and knee osteoarthritis, Part II: OARSI evidence- based, expert consensus guidelines. Osteoarthritis Carti- lage 2008;16(2):137-62.
14. Basurto Ona X, Rigau Comas D, Urrútia G. Opioids for acute pancreatitis pain. Cochrane Database Syst Rev 2013;7:CD009179.
15. King SJ, Reid C, Forbes K, Hanks G. A systematic review of oxycodone in the management of cancer pain. Palliat Med 2011;25(5):454-70.
16. Wang YM, Liu ZW, Liu JL, Zhang L. Efcacy and tolerability of oxycodone in moderate-severe cancer-related pain: A me- ta-analysis of randomized controlled trials. Exp Ther Med 2012;4(2):249-54.
17. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efcacy and safety. Pain 2004;112(3):372-80.
18. Mercadante S. Prospects and challenges in opioid analgesia for pain management. Curr Med Res Opin 2011;27(9):1741- 3.
19. Abramowitz L, Béziaud N, Labreze L, Giardina V, Caussé C, Chuberre B, et al. Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross- sectional survey of 520 patients with cancer pain: DYON- ISOS study. J Med Econ 2013;16(12):1423-33.
20. Kokki H, Kokki M, Sjövall S. Oxycodone for the treat- ment of postoperative pain. Expert Opin Pharmacother 2012;13(7):1045-58.
21. Klimas R, Witticke D, El Fallah S, Mikus G. Contribution of oxycodone and its metabolites to the overall analgesic ef- fect after oxycodone administration. Expert Opin Drug Metab Toxicol 2013;9(5):517-28.
22. Medline Plus. Oxycodone. 2013; http://www.nlm.nih.gov/ medlineplus/druginfo/meds/a682132.html. Accessed 3 July, 2014.
23. Duthey B, Scholten W. Adequacy of opioid analgesic con- sumption at country, global, and regional levels in 2010, its relationship with development level, and changes com- pared with 2006. J Pain Symptom Manage 2014;47(2):283- 97.
24. Group PPS. Opioid Consumption Data, Countries. 2013; http://www.painpolicy.wisc.edu/countryprofles. Accessed Feb 8, 2014.
25. Kotlinska-Lemieszek A, Paulsen O, Kaasa S, Klepstad P. Poly- pharmacy in patients with advanced cancer and pain: a Eu- ropean cross-sectional study of 2282 patients. J Pain Symp- tom Manage 2014;48(6):1145-59.
26. Treat the Pain. Treat the Pain. 2014; http://www.treatthe- pain.org/. Accessed 23 June, 2014.
27. Treat the Pain. Data. 2014; http://www.treatthepain.org/ data.html. Accessed 23 June, 2014.
28. Treat the Pain. Turkey. Country Snapshot 2014; http://www. treatthepain.org/Assets/CountryReports/Turkey.pdf. Ac- cessed 23 June, 2014.
29. Fisch MJ, Lee JW, Weiss M, Wagner LI, Chang VT, Cella D, et al. Prospective, observational study of pain and anal- gesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. J Clin Oncol 2012;30(16):1980-8.
30. Mercadante S. Opioid titration in cancer pain: a critical re- view. Eur J Pain 2007;11(8):823-30.
31. Gilson AM, Maurer MA, Joranson DE. State medical board members beliefs about pain, addiction, and diversion and abuse: a changing regulatory environment. J Pain 2007;8(9):682-91.
32. Primm BJ, Perez L, Dennis GC, Benjamin L, Clark W, Keough K, et al. Managing pain: The Challenge in Underserved Populations: Appropriate Use Versus Abuse and Diversion. J Natl Med Assoc 2004;96(9):1152-61.
33. Glajchen M. Chronic pain: treatment barriers and strategies for clinical practice. J Am Board Fam Pract 2001;14(3):211-8.
34. Manchikanti L. Prescription drug abuse: what is being done to address this new drug epidemic? Testimony before the Subcommittee on Criminal Justice, Drug Policy and Human Resources. Pain Physician 2006;9(4):287-321.
35. McCracken LM, Hoskins J, Eccleston C. Concerns about medication and medication use in chronic pain. J Pain 2006;7(10):726-34.
36. Rhodin A. The rise of opiophobia: is history a barrier to pre- scribing? J Pain Palliat Care Pharmacother 2006;20(3):31-2.
37. Rupp T, Delaney KA. Inadequate analgesia in emergency medicine. Ann Emerg Med 2004;43(4):494-503.
38. Brennan MJ, Stanos S. Strategies to optimize pain manage- ment with opioids while minimizing risk of abuse. PM R 2010;2(6):544-58.
39. Manchikanti L, Giordano J, Boswell MV, Fellows B, Manchu- konda R, Pampati V. Psychological factors as predictors of opioid abuse and illicit drug use in chronic pain patients. J Opioid Manag 2007;3(2):89-100.
40. Sullivan MD, Von Korf M, Banta-Green C, Merrill JO, Saun- ders K. Problems and concerns of patients receiving chronic opioid therapy for chronic non-cancer pain. Pain 2010;149(2):345-53.
41. Compton WM, Volkow ND. Abuse of prescription drugs and the risk of addiction. Drug Alcohol Depend 2006;83 Suppl 1:4-7.
42. Passik SD. Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc 2009;84(7):593-601.
43. Del Fabbro E. Assessment and management of chemical cop- ing in patients with cancer. J Clin Oncol 2014;32(16):1734-8.
44. Passik SD, Lowery A. Psychological variables potentially im- plicated in opioid-related mortality as observed in clinical practice. Pain Med 2011;12 Suppl 2:36-42.
45. Butler SF, Black RA, Cassidy TA, Dailey TM, Budman SH. Abuse risks and routes of administration of diferent pre- scription opioid compounds and formulations. Harm Re- duct J 2011;8:29.
46. Freud T, Sherf M, Battat E, Vardy D, Shvartzman P. Patterns of opioid consumption in cancer patients. Isr Med Assoc J 2013;15(2):89-93.
47. Gimbel J, Ahdieh H. The efcacy and safety of oral imme- diate-release oxymorphone for postsurgical pain. Anesth Analg 2004;99(5):1472-7.
48. Ahmedzai SH, Nauck F, Bar-Sela G, Bosse B, Leyendecker P, Hopp M. A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efcacy of oxycodone/naloxone prolonged- release tablets in patients with moderate/severe, chronic cancer pain. Palliat Med 2012;26(1):50-60.
49. Gatti A, Sabato E, Di Paolo AR, Mammucari M, Sabato AF. Oxycodone/paracetamol: a low-dose synergic combination useful in diferent types of pain. Clin Drug Investig 2010;30 Suppl 2:3-14.
50. Gatti A, Sabato AF, Occhioni R, Colini Baldeschi G, Reale C. Controlled-release oxycodone and pregabalin in the treat- ment of neuropathic pain: results of a multicenter Italian study. Eur Neurol 2009;61(3):129-37.
51. Hanna M, OBrien C, Wilson MC. Prolonged-release oxy- codone enhances the efects of existing gabapentin ther- apy in painful diabetic neuropathy patients. Eur J Pain 2008;12(6):804-13.
52. Zare MA, Ghalyaie AH, Fathi M, Farsi D, Abbasi S, Hafezi- moghadam P. Oral oxycodone plus intravenous acetamino- phen versus intravenous morphine sulfate in acute bone fracture pain control: a double-blind placebo-controlled randomized clinical trial. Eur J Orthop Surg Traumatol 2014;24(7):1305-9.
53. Mercadante S, Giarratano A. Combined oral prolonged- release oxycodone and naloxone in chronic pain manage- ment. Expert Opin Investig Drugs 2013;22(1):161-6.
54. Scharnagel R, Kaiser U, Schütze A, Heineck R, Gossrau G, Sabatowski R. Chronic non-cancer-related pain. Long-term treatment with rapid-release and short-acting opioids in the context of misuse and dependency. [Article in German] Schmerz 2013;27(1):7-19. [Abstract]
55. Taylor R Jr, Rafa RB, Pergolizzi JV Jr. Controlled release for- mulation of oxycodone in patients with moderate to severe chronic osteoarthritis: a critical review of the literature. J Pain Res 2012;5:77-87.
56. Friedman BW, West J, Vinson DR, Minen MT, Restivo A, Galla- gher EJ. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambula- tory Medical Care Survey. Cephalalgia 2014 Jun 19.
57 Pergolizzi JV. Quantifying the impact of drug-drug interac- tions associated with opioids. Am J Manag Care 2011;17 Suppl 11:288-92.
58. Pergolizzi JV Jr, Labhsetwar SA, Puenpatom RA, Joo S, Ben- Joseph RH, Summers KH. Prevalence of exposure to po- tential CYP450 pharmacokinetic drug-drug interactions among patients with chronic low back pain taking opioids. Pain Pract 2011;11(3):230-9.
59. Heiskanen T, Kalso E. Non-analgesic efects of opioids: inter- actions between opioids and other drugs. Curr Pharm Des 2012;18(37):6079-89.
60. Söderberg Löfdal KC, Andersson ML, Gustafsson LL. Cyto- chrome P450-mediated changes in oxycodone pharmaco- kinetics/pharmacodynamics and their clinical implications. Drugs 2013;73(6):533-43.
61. Pedersen KV, Olesen AE, Drewes AM, Osther PJ. Morphine versus oxycodone analgesia after percutaneous kidney stone surgery: a randomised double blinded study. Uroli- thiasis 2013;41(5):423-30.
62. Reid CM, Martin RM, Sterne JA, Davies AN, Hanks GW. Oxy- codone for cancer-related pain: meta-analysis of random- ized controlled trials. Arch Intern Med 2006;166(8):837-43.
63. Koyyalagunta D, Bruera E, Solanki DR, Nouri KH, Burton AW, Toro MP, et al. A systematic review of randomized trials on the efectiveness of opioids for cancer pain. Pain Physician 2012;15(3 Suppl):ES39-58.
64. Rothwell MP, Pearson D, Hunter JD, Mitchell PA, Graham-Woollard T, Goodwin L, et al. Oral oxycodone ofers equivalent analgesia to intravenous patient-controlled analgesia after total hip replacement: a randomized, single- centre, non-blinded, non-inferiority study. Br J Anaesth 2011;106(6):865-72.
65. Yu S, Yu L, Hou Y, Han JH, Richards H. Safety and efcacy of once-daily hydromorphone extended-release versus twice- daily oxycodone HCl controlled release in cancer pain: a phase 3, randomized, double-blind, multi-center study in Chinese patients. Singapore: 5th Assoication of South-East Asian Pain Societies Conference; 2013;2-5.
66. Dieterich M, Müller-Jordan K, Stubert J, Kundt G, Wagner K, Gerber B. Pain management after cesarean: a randomized controlled trial of oxycodone versus intravenous piritra- mide. Arch Gynecol Obstet 2012;286(4):859-65.
67. Lenz H, Sandvik L, Qvigstad E, Bjerkelund CE, Raeder J. A comparison of intravenous oxycodone and intrave- nous morphine in patient-controlled postoperative an- algesia after laparoscopic hysterectomy. Anesth Analg 2009;109(4):1279-83.
68. Ho HS. Patient-controlled analgesia versus oral controlled- release oxycodone - are they interchangeable for acute postoperative pain after laparoscopic colorectal surgeries? Oncology 2008;74 Suppl 1:61-5.
69. Pergolizzi JV Jr, Taylor R Jr, Nalamachu S, Rafa RB, Carlson DR, Varanasi RK, 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.
70. Lugo RA, Kern SE. The pharmacokinetics of oxycodone. J Pain Palliat Care Pharmacother 2004;18(4):17-30.
71. Anastassopoulos KP, Chow W, Ackerman SJ, Tapia C, Benson C, Kim MS. Oxycodone-related side efects: impact on de- gree of bother, adherence, pain relief, satisfaction, and qual- ity of life. J Opioid Manag 2011;7(3):203-15.
72. Salzman RT, Roberts MS, Wild J, Fabian C, Reder RF, Golden- heim PD. Can a controlled-release oral dose form of oxyco- done be used as readily as an immediate-release form for the purpose of titrating to stable pain control? J Pain Symp- tom Manage 1999;18(4):271-9.
73. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: char- acteristics and impact in patients with cancer pain. Pain 1999;81(1-2):129-34.
74. Portenoy RK, Bennett DS, Rauck R, Simon S, Taylor D, Bren- nan M, et al. Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain. J Pain 2006;7(8):583-91.
75. Højsted J, Nielsen PR, Eriksen J, Hansen OB, Sjøgren P. Break- through pain in opioid-treated chronic non-malignant pain patients referred to a multidisciplinary pain centre: a pre- liminary study. Acta Anaesthesiol Scand 2006;50(10):1290-6.
76. Kurita GP, Tange UB, Farholt H, Sonne NM, Strömgren AS, Ankersen L, et al. Pain characteristics and manage- ment of inpatients admitted to a comprehensive cancer centre: a cross-sectional study. Acta Anaesthesiol Scand 2013;57(4):518-25.
77. Gatti A, Mediati RD, Reale C, Cuomo A, Vellucci R, Russo G, et al. Breakthrough pain in patients referred to pain clin- ics: the Italian pain network retrospective study. Adv Ther 2012;29(5):464-72.
78. Gatti A, Gentili M, Iorno V, Mammucari M, Tufaro G, Lazzari M, et al. Beyond the traditional defnition of breakthrough pain: an observational study. Adv Ther 2013;30(3):298-305.
79. Davies A, Zeppetella G, Andersen S, Damkier A, Vejlgaard T, Nauck F, et al. Multi-centre European study of breakthrough cancer pain: pain characteristics and patient perceptions of current and potential management strategies. Eur J Pain 2011;15(7):756-63.
80. Webber K, Davies AN, Cowie MR. Breakthrough pain: a qual- itative study involving patients with advanced cancer. Sup- port Care Cancer 2011;19(12):2041-6.
81. Zeppetella G, Davies AN. Opioids for the management of breakthrough pain in cancer patients. Cochrane Database Syst Rev 2013 Oct 21;10:CD004311.
82. Portenoy RK, Bruns D, Shoemaker B, Shoemaker SA. Break- through pain in community-dwelling patients with cancer pain and noncancer pain, part 2: impact on function, mood, and quality of life. J Opioid Manag 2010;6(2):109-16.
83. Portenoy RK, Bruns D, Shoemaker B, Shoemaker SA. Break- through pain in community-dwelling patients with cancer pain and noncancer pain, part 1: prevalence and character- istics. J Opioid Manag 2010;6(2):97-108.
84. NCCN. Adult Cancer Pain. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014; Version 2.2014. Avail- able at: http://www.nccn.org/professionals/physician_gls/ PDF/pain.pdf. Accessed 4 July, 2014.
85. Dumas EO, Pollack GM. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J 2008;10(4):537-51.
86. Bell K, Salmon A. Pain, physical dependence and pseudo- addiction: redefning addiction for nice people? Int J Drug Policy 2009;20(2):170-8.
87. Portenoy RK, Savage SR. Clinical realities and economic considerations: special therapeutic issues in intrathecal therapy--tolerance and addiction. J Pain Symptom Manage 1997;14(3 Suppl):27-35.
88. Pergolizzi JV Jr, Gharibo C, Passik S, Labhsetwar S, Taylor R Jr, Pergolizzi JS, et al. Dynamic risk factors in the misuse of opioid analgesics. J Psychosom Res 2012;72(6):443-51.
89. Pergolizzi J, Pappagallo M, Staufer J, Gharibo C, Fortner N, De Jesus MN, et al. The role of urine drug testing for patients on opioid therapy. Pain Pract 2010;10(6):497-507.
90. Chou R, Fanciullo GJ, Fine PG, Miaskowski C, Passik SD, Portenoy RK. Opioids for chronic noncancer pain: predic- tion and identifcation 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(2):131-46.
91. Back SE, Payne RA, Waldrop AE, Smith A, Reeves S, Brady KT. Prescription opioid aberrant behaviors: a pilot study of sex diferences. Clin J Pain 2009;25(6):477-84.
92. Butler SF, Fernandez K, Benoit C, Budman SH, Jamison RN. Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). J Pain 2008;9(4):360-72.
93. Koyyalagunta D, Bruera E, Aigner C, Nusrat H, Driver L, Novy D. Risk stratifcation of opioid misuse among patients with cancer pain using the SOAPP-SF. Pain Med 2013;14(5):667-75.
94. Anghelescu DL, Ehrentraut JH, Faughnan LG. Opioid misuse and abuse: risk assessment and management in patients with cancer pain. J Natl Compr Canc Netw 2013;11(8):1023- 31.
95. Boscarino JA, Rukstalis M, Hofman SN, Han JJ, Erlich PM, Gerhard GS, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction 2010;105(10):1776-82.
96. Baldacchino A, Gilchrist G, Fleming R, Bannister J. Guilty un- til proven innocent: a qualitative study of the management of chronic non-cancer pain among patients with a history of substance abuse. Addict Behav 2010;35(3):270-2.
97. Compton P. Should opioid abusers be discharged from opi- oid-analgesic therapy? Pain Med 2008;9(4):383-90.
98. Compton P. Managing a drug abusers pain. Nursing 1999;29(5):26-8.
99. 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(2):173-81.
100. Passik SD, Portenoy RK, Ricketts PL. Substance abuse issues in cancer patients. Part 1: Prevalence and diagnosis. Oncol- ogy (Williston Park) 1998;12(4):517-24.
101. LeQuang J, Pergolizzi J. Chemotherapy-induced peripheral neuropathy: review of clinical studies. Boca Raton, Florida: CRC Press; 2012.