A Guide for Cancer Pain Management in Latin America
Keywords:Cancer pain, Latin America cancer pain, opioids, opioid therapy.
Cancer prevalence in Latin America (LATAM) is increasing and represents a major cause of morbidity and mortality. Managing cancer patients—who live longer than ever before—requires appropriate management of cancer pain, described by the World Health Organization (WHO) in 1988 with its now famous “pain ladder,” the rungs of which represented nonopioids, weak opioids, and strong opioids as pain relievers. Yet even today much cancer pain is undertreated. Cancer pain can be multimechanistic with a neuropathic component which may complicate pain control. Acute pain should be treated aggressively to avoid the potential transition to chronic pain, a maladaptive form of pain that can be particularly challenging to treat. Although opioids have been recognized by WHO in 1988 and since then as a safe, effective form for treating moderate to severe cancer pain, opioid consumption in LATAM nations is very low. LATAM countries make up about 9% of the world’s population but represent only about 1% of global opioid consumption. Better education about pain control in cancer and opioid therapy is needed by both healthcare providers and patients to better treat cancer pain in LATAM. But opioid-associated side effects and the risk of abuse and diversion are important risks of opioid therapy that are to be fully understood by both healthcare providers and patients before commencing therapy. Opioid risk management plans balance the need for access to opioids for appropriate patients with the mitigation of opioid-related risks of abuse and addiction. Risks as well as benefits should be clearly understood in order to consider opioid therapy. Combining education, prescription drug monitoring plans, and other risk mitigation strategies may be useful tools. Abuse-deterrent formulations, such as fixed-dose combination products of an opioid with naloxone, have been designed to resist abuse. LATAM may benefit from such new products in efforts to bring better pain control to cancer patients in a rational and responsible manner.
Bray F, Pineros M. Cancer patterns, trends and projections in Latin America and the Caribbean: a global context. Salud publica de Mexico 2016; 58(2): 104-117. https://doi.org/10.21149/spm.v58i2.7779
Pan American Health Organization. Health in the Americas. Washington, DC: World Health Organization; 2002.
Raez LE, Santos ES, Rolfo C, et al. Challenges in Facing the Lung Cancer Epidemic and Treating Advanced Disease in Latin America. Clinical lung cancer 2016.
Goss PE, Lee BL, Badovinac-Crnjevic T, et al. Planning cancer control in Latin America and the Caribbean. The lancet oncology 2013; 14(5): 391-436. https://doi.org/10.1016/S1470-2045(13)70048-2
Pow-Sang M, Destefano V, Astigueta JC, et al. Prostate cancer in Latin America. Actas urologicas espanolas 2009; 33(10): 1057-1061. https://doi.org/10.1016/S0210-4806(09)73181-X
van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2007; 18(9): 1437-1449. https://doi.org/10.1093/annonc/mdm056
Gupta M, Sahi MS, Bhargava AK, Talwar V. A Prospective Evaluation of Symptom Prevalence and Overall Symptom Burden Among Cohort of Critically Ill Cancer Patients. Indian journal of palliative care 2016; 22(2): 118-124. https://doi.org/10.4103/0973-1075.179601
Alifrangis C, Koizia L, Rozario A, et al. The experiences of cancer patients. QJM: monthly journal of the Association of Physicians 2011; 104(12): 1075-1081. https://doi.org/10.1093/qjmed/hcr129
Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro-oncology 2012; 14 Suppl 4: iv45-54.
LeQuang J, Pergolizzi J. Chemotherapy-induced peripheral neuropathy: review of clinical studies. Boca Raton, Florida: CRC Press; 2012.
World Health Organization. WHO's pain ladder for adults 1988; http/:/www.who.int/cancer/palliative/painladder/en/. Accessed 7 May, 2013.
Maxwell JC. The prescription drug epidemic in the United States: a perfect storm. Drug and alcohol review 2011; 30(3): 264-270. https://doi.org/10.1111/j.1465-3362.2011.00291.x
Dowell D, Haegerich T, R C. CDC Guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm Rep 2016; 65(1): 1-49. https://doi.org/10.15585/mmwr.rr6501e1
Daher M. Pain relief is a human right. Asian Pacific journal of cancer prevention: APJCP 2010; 11 Suppl 1: 97-101.
Brennan F, Carr DB, Cousins M. Pain management: a fundamental human right. Anesthesia and analgesia 2007; 105(1): 205-221. https://doi.org/10.1213/01.ane.0000268145.52345.55
Fisch MJ, Lee JW, Weiss M, et al. Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2012; 30(16): 1980-1988. https://doi.org/10.1200/JCO.2011.39.2381
Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. The New England journal of medicine 1994; 330(9): 592-596. https://doi.org/10.1056/NEJM199403033300902
Pergolizzi JV, Gharibo C, Ho KY. Treatment Considerations for Cancer Pain: A Global Perspective. Pain practice: the official journal of World Institute of Pain 2014.
Ferris FD, Bruera E, Cherny N, et al. Palliative cancer care a decade later: accomplishments, the need, next steps -- from the American Society of Clinical Oncology. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2009; 27(18): 3052-3058. https://doi.org/10.1200/JCO.2008.20.1558
Twycross R. [Pain treatment in cancer patients.]. Schmerz (Berlin, Germany) 1990; 4(2): 65-74. https://doi.org/10.1007/BF02527837
Pergolizzi J. Chronic pain--moving from symptom control to mechanism-based treatment. Current medical research and opinion 2011; 27(10): 2079-2080. https://doi.org/10.1185/03007995.2011.619446
Leon MX, De Lima L, Florez S, et al. Improving availability of and access to opioids in Colombia: description and preliminary results of an action plan for the country. Journal of pain and symptom management 2009; 38(5): 758-766. https://doi.org/10.1016/j.jpainsymman.2009.03.007
Montgomery K, Hurley R. Nerve destruction for the alleviation of visceral pain. Vol 4. Philadelphia: Elsevier Saunders; 2013.
Rocha AP, Kraychete DC, Lemonica L, et al. Pain: current aspects on peripheral and central sensitization. Revista brasileira de anestesiologia 2007; 57(1): 94-105. https://doi.org/10.1590/S0034-70942007000100011
Pergolizzi JV, Jr., Raffa RB, Taylor R, Jr. Treating acute pain in light of the chronification of pain. Pain management nursing: official journal of the American Society of Pain Management Nurses 2014; 15(1): 380-390. https://doi.org/10.1016/j.pmn.2012.07.004
Apkarian AV, Baliki MN, Farmer MA. Predicting transition to chronic pain. Current opinion in neurology 2013; 26(4): 360-367. https://doi.org/10.1097/WCO.0b013e32836336ad
Deumens R, Steyaert A, Forget P, et al. Prevention of chronic postoperative pain: cellular, molecular, and clinical insights for mechanism-based treatment approaches. Progress in neurobiology 2013; 104: 1-37. https://doi.org/10.1016/j.pneurobio.2013.01.002
Woolf CJ. Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life sciences 2004; 74(21): 2605-2610. https://doi.org/10.1016/j.lfs.2004.01.003
Bulkley J, McMullen CK, Hornbrook MC, et al. Spiritual well-being in long-term colorectal cancer survivors with ostomies. Psycho-oncology 2013; 22(11): 2513-2521. https://doi.org/10.1002/pon.3318
Lacasse A, Bourgault P, Choiniere M. Fibromyalgia-related costs and loss of productivity: a substantial societal burden. BMC musculoskeletal disorders 2016; 17: 168. https://doi.org/10.1186/s12891-016-1027-6
Alsaadi SM, McAuley JH, Hush JM, Maher CG. Prevalence of sleep disturbance in patients with low back pain. European spine journal: official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 2011; 20(5): 737-743. https://doi.org/10.1007/s00586-010-1661-x
Sun V, Grant M, Wendel CS, et al. Sexual Function and Health-Related Quality of Life in Long-Term Rectal Cancer Survivors. The journal of sexual medicine 2016; 13(7): 1071-1079. https://doi.org/10.1016/j.jsxm.2016.05.005
Verrocchio MC, Carrozzino D, Marchetti D, Andreasson K, Fulcheri M, Bech P. Mental Pain and Suicide: A Systematic Review of the Literature. Frontiers in psychiatry 2016; 7: 108. https://doi.org/10.3389/fpsyt.2016.00108
Fassberg MM, Cheung G, Canetto SS, et al. A systematic review of physical illness, functional disability, and suicidal behaviour among older adults. Aging & mental health 2016; 20(2): 166-194. https://doi.org/10.1080/13607863.2015.1083945
Mohler MJ, Coons SJ, Hornbrook MC, et al. The health-related quality of life in long-term colorectal cancer survivors study: objectives, methods and patient sample. Current medical research and opinion 2008; 24(7): 2059-2070. https://doi.org/10.1185/03007990802118360
Liedgens H, Obradovic M, De Courcy J, Holbrook T, Jakubanis R. A burden of illness study for neuropathic pain in Europe. ClinicoEconomics and outcomes research: CEOR 2016; 8: 113-126.
Chopra I, Kamal KM. A systematic review of quality of life instruments in long-term breast cancer survivors. Health and quality of life outcomes 2012; 10: 14. https://doi.org/10.1186/1477-7525-10-14
NCCN. Adult Cancer Pain. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014; Version 2.2014. Available at: http/:/www.nccn.org/professionals/ physician_gls/PDF/pain.pdf. Accessed 4 July, 2014.
Trescot AM. Review of the role of opioids in cancer pain. Journal of the National Comprehensive Cancer Network: JNCCN 2010; 8(9): 1087-1094. https://doi.org/10.6004/jnccn.2010.0077
Hastie BA, Gilson AM, Maurer MA, Cleary JF. An examination of global and regional opioid consumption trends 1980-2011. Journal of pain & palliative care pharmacotherapy 2014; 28(3): 259-275. https://doi.org/10.3109/15360288.2014.941132
Gilson AM, Maurer MA, Ryan KM, Rathouz PJ, Cleary JF. Using a morphine equivalence metric to quantify opioid consumption: examining the capacity to provide effective treatment of debilitating pain at the global, regional, and country levels. Journal of pain and symptom management 2013; 45(4): 681-700. https://doi.org/10.1016/j.jpainsymman.2012.03.011
Berterame S, Erthal J, Thomas J, et al. Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 2016; 387(10028): 1644-1656. https://doi.org/10.1016/S0140-6736(16)00161-6
Duthey B, Scholten W. Adequacy of opioid analgesic consumption at country, global, and regional levels in 2010, its relationship with development level, and changes compared with 2006. Journal of pain and symptom management 2014; 47(2): 283-297. https://doi.org/10.1016/j.jpainsymman.2013.03.015
Moyano JR, Figueras A. The medical consumption of opioids in Colombia, 1997-2007. Journal of pain & palliative care pharmacotherapy 2010; 24(4): 367-373. https://doi.org/10.3109/15360288.2010.523067
Florez-Rojas S, Delgado M. [Availability and barriers to opioid access in Colombia: the experience of an academic institution]. Universitas Medica 2011; 52(2): 140-148.
Dalal S, Bruera E. Access to opioid analgesics and pain relief for patients with cancer. Nat Rev Clin Oncol 2013; 10(2): 108-116. https://doi.org/10.1038/nrclinonc.2012.237
Breuer B, Fleishman SB, Cruciani RA, Portenoy RK. Medical oncologists' attitudes and practice in cancer pain management: a national survey. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2011; 29(36): 4769-4775. https://doi.org/10.1200/JCO.2011.35.0561
Zhang Q, Yu C, Feng S, et al. Physicians' Practice, Attitudes Toward, and Knowledge of Cancer Pain Management in China. Pain medicine (Malden, Mass) 2015; 16(11): 2195-2203. https://doi.org/10.1111/pme.12819
Srisawang P, Harun-Or-Rashid M, Hirosawa T, Sakamoto J. Knowledge, attitudes and barriers of physicians, policy makers/regulators regarding use of opioids for cancer pain management in Thailand. Nagoya journal of medical science 2013; 75(3-4): 201-212.
Kim MH, Park H, Park EC, Park K. Attitude and knowledge of physicians about cancer pain management: young doctors of South Korea in their early career. Japanese journal of clinical oncology 2011; 41(6): 783-791. https://doi.org/10.1093/jjco/hyr043
De Silva BS, Rolls C. Attitudes, beliefs, and practices of Sri Lankan nurses toward cancer pain management: an ethnographic study. Nursing & health sciences 2011; 13(4): 419-424. https://doi.org/10.1111/j.1442-2018.2011.00635.x
Kaki AM. Medical students' knowledge and attitude toward cancer pain management in Saudi Arabia. Saudi medical journal 2011; 32(6): 628-632.
Liang SY, Tung HH, Wu SF, et al. Concerns about pain and prescribed opioids in Taiwanese oncology outpatients. Pain management nursing: official journal of the American Society of Pain Management Nurses 2013; 14(4): 336-342. https://doi.org/10.1016/j.pmn.2011.08.004
Akiyama M, Takebayashi T, Morita T, et al. Knowledge, beliefs, and concerns about opioids, palliative care, and homecare of advanced cancer patients: a nationwide survey in Japan. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer 2012; 20(5): 923-931. https://doi.org/10.1007/s00520-011-1161-5
Ogboli-Nwasor E, Makama J, Yusufu L. Evaluation of knowledge of cancer pain management among medical practitioners in a low-resource setting. Journal of pain research 2013; 6: 71-77. https://doi.org/10.2147/JPR.S38588
Chen CH, Tang ST, Chen CH. Meta-analysis of cultural differences in Western and Asian patient-perceived barriers to managing cancer pain. Palliative medicine 2012; 26(3): 206-221. https://doi.org/10.1177/0269216311402711
Martinez KA, Aslakson RA, Wilson RF, et al. A systematic review of health care interventions for pain in patients with advanced cancer. The American journal of hospice & palliative care 2014; 31(1): 79-86. https://doi.org/10.1177/1049909113476129
Tateno Y, Ishikawa S. Clinical pathways can improve the quality of pain management in home palliative care in remote locations: retrospective study on Kozu Island, Japan. Rural and remote health 2012; 12: 1992.
Torres Vigil I, Aday LA, De Lima L, Cleeland CS. What predicts the quality of advanced cancer care in Latin America? A look at five countries: Argentina, Brazil, Cuba, Mexico, and Peru. Journal of pain and symptom management 2007; 34(3): 315-327. https://doi.org/10.1016/j.jpainsymman.2006.11.015
Breivik H, Cherny N, Collett B, et al. Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2009; 20(8): 1420-1433. https://doi.org/10.1093/annonc/mdp001
Caraceni A, Martini C, Zecca E, et al. Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliative medicine 2004; 18(3): 177-183. https://doi.org/10.1191/0269216304pm890oa
Davies A, Buchanan A, Zeppetella G, et al. Breakthrough cancer pain: an observational study of 1000 European oncology patients. Journal of pain and symptom management 2013; 46(5): 619-628. https://doi.org/10.1016/j.jpainsymman.2012.12.009
Swarm RA, Abernethy AP, Anghelescu DL, et al. Adult cancer pain. Journal of the National Comprehensive Cancer Network: JNCCN 2013; 11(8): 992-1022. https://doi.org/10.6004/jnccn.2013.0119
Nalamachu SR. Opioid rotation in clinical practice. Advances in therapy 2012; 29(10): 849-863. https://doi.org/10.1007/s12325-012-0051-7
Cleary J, De Lima L, Eisenchlas J, Radbruch L, Torode J, Cherny NI. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Latin America and the Caribbean: a report from the Global Opioid Policy Initiative (GOPI). Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2013; 24 Suppl 11: xi41-50.
Bandieri E, Romero M, Ripamonti CI, et al. Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2016; 34(5): 436-442. https://doi.org/10.1200/JCO.2015.61.0733
Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. The New England journal of medicine 2009; 361(8): 827-828. https://doi.org/10.1056/NEJMc0904266
Corli O, Floriani I, Roberto A, et al. Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2016; 27(6): 1107-1115. https://doi.org/10.1093/annonc/mdw097
Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. The lancet oncology 2012; 13(2): e58-68. https://doi.org/10.1016/S1470-2045(12)70040-2
Maltoni M, Scarpi E, Modonesi C, et al. A validation study of the WHO analgesic ladder: a two-step vs three-step strategy. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer 2005; 13(11): 888-894. https://doi.org/10.1007/s00520-005-0807-6
Raffa RB, Pergolizzi JV, Jr. A modern analgesics pain 'pyramid'. Journal of clinical pharmacy and therapeutics 2014; 39(1): 4-6. https://doi.org/10.1111/jcpt.12110
Noble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane database of systematic reviews (Online) 2010(1): CD006605.
Abramowitz L, Beziaud N, Labreze L, et al. Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS study. Journal of medical economics 2013; 16(12): 1423-1433. https://doi.org/10.3111/13696998.2013.851082
Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. The American journal of gastroenterology 2011; 106(5): 835-842; quiz 843. https://doi.org/10.1038/ajg.2011.30
Leppert W. Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction. Drug design, development and therapy 2015; 9: 2215-2231. https://doi.org/10.2147/DDDT.S32684
International Pain Summit Of The International Association For The Study Of P. Declaration of Montreal: declaration that access to pain management is a fundamental human right. Journal of pain & palliative care pharmacotherapy 2011; 25(1): 29-31. https://doi.org/10.3109/15360288.2010.547560
U.S. Congress. One hundred eleventh Congress of the United States of America at the Second SessionL An Act Entitled the Patient Protection and Affordable Care Act 2010; H.R. 3590: https/:/www.gpo.gov/fdsys/pkg/BILLS-111hr3590enr/pdf/BILLS-111hr3590enr.pdf. Accessed 31 March, 2016.
Aston G. Smart pain management makes good business sense. Hospitals & health networks / AHA 2012; 86(6): 38-40, 49-50, 31.
Manchikanti L, Helm S, 2nd, Fellows B, et al. Opioid epidemic in the United States. Pain physician 2012; 15(3 Suppl): ES9-38.
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. https://doi.org/10.1001/jamapsychiatry.2014.3043
Benak LD, Eccher D, McKinney RE, Smith CM. Prescription drug monitoring through the Maine Office of Substance Abuse. Journal of forensic nursing 2007; 3(3-4): 141-145. https://doi.org/10.1111/j.1939-3938.2007.tb00102.x
CDC. Prescription Drug Monitoring Programs (PDMPs). Injury Prevention & Control: Prescription Drug Overdose 2015; http/:/www.cdc.gov/drugoverdose/pdmp/. Accessed 11 January, 2016.
Buchman DZ, Ho A. What's trust got to do with it? Revisiting opioid contracts. Journal of medical ethics 2014; 40(10): 673-677. https://doi.org/10.1136/medethics-2013-101320
McGee S, Silverman RD. Treatment agreements, informed consent, and the role of state medical boards in opioid prescribing. Pain medicine (Malden, Mass) 2015; 16(1): 25-29. https://doi.org/10.1111/pme.12580
Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain medicine (Malden, Mass) 2005; 6(2): 107-112. https://doi.org/10.1111/j.1526-4637.2005.05031.x
Pergolizzi JV, Jr., Gharibo C, Passik S, et al. Dynamic risk factors in the misuse of opioid analgesics. Journal of psychosomatic research 2012; 72(6): 443-451. https://doi.org/10.1016/j.jpsychores.2012.02.009
Anghelescu DL, Ehrentraut JH, Faughnan LG. Opioid misuse and abuse: risk assessment and management in patients with cancer pain. Journal of the National Comprehensive Cancer Network: JNCCN 2013; 11(8): 1023-1031. https://doi.org/10.6004/jnccn.2013.0120
Akbik H, Butler SF, Budman SH, Fernandez K, Katz NP, Jamison RN. Validation and clinical application of the Screener and Opioid Assessment for Patients with Pain (SOAPP). Journal of pain and symptom management 2006; 32(3): 287-293. https://doi.org/10.1016/j.jpainsymman.2006.03.010
Butler SF, Budman SH, Fernandez KC, Fanciullo GJ, Jamison RN. Cross-Validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R). Journal of addiction medicine 2009; 3(2): 66-73. https://doi.org/10.1097/ADM.0b013e31818e41da
Barry DT, Irwin KS, Jones ES, et al. Opioids, chronic pain, and addiction in primary care. The journal of pain: official journal of the American Pain Society 2010; 11(12): 1442-1450. https://doi.org/10.1016/j.jpain.2010.04.002
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. Pharmacoepidemiology and drug safety 2013; 22(12): 1274-1282. https://doi.org/10.1002/pds.3522
Alexander L, Mannion RO, Weingarten B, Fanelli RJ, Stiles GL. Development and impact of prescription opioid abuse deterrent formulation technologies. Drug and alcohol dependence 2014; 138: 1-6. https://doi.org/10.1016/j.drugalcdep.2014.02.006
FDA. Guidance for Industry: abuse-deterrent opioids, evaluation and labeling 2013; http/:/www.fda.gov/downloads/ Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Accessed 25 April, 2013.
Pergolizzi JV, Jr., LeQuang JA. Abuse-deterrent formulations of opioid analgesics. Pain practice: the official journal of World Institute of Pain 2014; 14(3): 204-206. https://doi.org/10.1111/papr.12093
Pergolizzi JV, Jr., Zampogna G, Taylor R, Jr., Raffa RB. Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain. Expert review of neurotherapeutics 2015; 15(3): 231-238. https://doi.org/10.1586/14737175.2015.1015418
Raffa RB, Pergolizzi JV, Jr. Opioid formulations designed to resist/deter abuse. Drugs 2010; 70(13): 1657-1675. https://doi.org/10.2165/11537940-000000000-00000
Raffa RB, Pergolizzi JV, Jr., Muniz E, Taylor R, Jr., Pergolizzi J. Designing opioids that deter abuse. Pain research and treatment 2012; 2012: 282981. https://doi.org/10.1155/2012/282981
Raffa RB, Taylor R, Jr., Pergolizzi JV, Jr. Sequestered naltrexone in sustained release morphine or oxycodone - a way to inhibit illicit use? Expert opinion on drug safety 2014; 13(2): 181-190. https://doi.org/10.1517/14740338.2013.841136
Mercadante S, Giarratano A. Combined oral prolonged-release oxycodone and naloxone in chronic pain management. Expert opinion on investigational drugs 2013; 22(1): 161-166. https://doi.org/10.1517/13543784.2013.752460
Bell T, Annunziata K, Leslie JB. Opioid-induced constipation negatively impacts pain management, productivity, and health-related quality of life: findings from the National Health and Wellness Survey. Journal of opioid management 2009; 5(3): 137-144.
Burness CB, Keating GM. Oxycodone/Naloxone prolonged-release: a review of its use in the management of chronic pain while counteracting opioid-induced constipation. Drugs 2014; 74(3): 353-375. https://doi.org/10.1007/s40265-014-0177-9