Prescribing drugs of dependence in general practice

Part C1 - Opioids

Patient selection for opioid therapy

Part C1 - Opioids
    6. Patient selection for opioid therapy
Download PDF

Last revised: 22 Jun 2020

GPs should be aware that certain patient groups have increased risks of harm in association with opioid use. As part of a patient selection and risk stratification approach, the following patient group attributes should be considered.

Most drugs that are used for pain management cross the placenta. The Australian Drug Evaluation Committee (ADEC) classifies drugs according to fetal risk and notes that there are particular times of concern during pregnancy: weeks 4–10 (organogenesis), and just before delivery. Opioid analgesics taken just before delivery may cause respiratory depression in the newborn, and withdrawal effects may occur in neonates of dependent mothers.

It is always better to avoid drugs during pregnancy. If medication for constant pain relief is required during pregnancy, consultation should occur with a specialist obstetrician or pain physician.

In practice

Prescribers should avoid initiating opioid therapy in pregnant women whenever possible. It is accepted that prescription of ORT for pregnant women with opioid-related substance misuse is a harm minimisation strategy.
For pregnant women already on opioids, opioid therapy should be tapered to the lowest effective dose slowly enough to avoid withdrawal symptoms and then discontinued if possible.194 GPs should access appropriate expertise if considering tapering opioids because of possible risk to the woman and to the fetus if withdrawal occurs.15

During breastfeeding, occasional doses of opioids are considered safe, but codeine should be avoided. Use repeated doses with caution, especially if the infant is premature or under four weeks of age. The infant should be monitored for sedation and other adverse effects.77

Patients on workers’ compensation are at risk of being prescribed high-dose opioids, because of higher levels of psychological distress, poorer surgical outcomes and protracted involvement in legal proceedings.195

It is well recognised that patients who are psychologically distressed after a work injury have poorer outcomes.196,197 Therefore, as soon as distress is recognised (even at the first consultation), the patient should be referred to an appropriate health professional (commonly a psychologist) and therapeutic steps undertaken to minimise opioid use.

Evidence also shows that, where possible and appropriate, returning to work has substantial benefits in improving patient morbidity and decreasing mortality.198 When assessing the capacity of the patient to return to work, patient self-assessment of ability is usually reliable, if it matches clinician impression. Activity is not limited to work but includes the usual activities that the patient undertakes in sport, recreation and at home.

For low back pain, patients are most at risk of developing chronic pain syndrome in the period between 8–12 weeks following the date of pain onset.199,200 However, recovery rates are not improved by commencing a new activity program in the first 4–6 weeks after injury.201,202

In practice

Clinicians and patients should be aware of the risks involved with workers’ compensation patients, and focus rehabilitation on increasing function, non-pharmacological approaches and keeping opioid analgesia to a minimum.

Returning to as much usual activity as soon as possible is the most important treatment for musculoskeletal injuries. For cases of increased complexity multidisciplinary involvement is beneficial, (refer to Prescribing drugs of dependence in general practice, Part C2: The role of opioids in general practice – Section 3.2 Multidisciplinary approach) including teamwork with specialists and a physiotherapist (refer to Prescribing drugs of dependence in general practice, Part C2: The role of opioids in general practice – Section 4.2 Activity and exercise interventions) with pain management experience.

Opioids can interfere with complex tasks such as driving due to sedation; diminished reaction times, reflexes and coordination; reduced peripheral vision due to the persistent miotic effects;203 and decreased ability to concentrate.204

There is little direct evidence that opioid analgesics (eg hydromorphone, morphine or oxycodone) have direct adverse effects on driving behaviour.205 The risk of accidents appears to increase in the first weeks of starting opioid therapy or after increasing the dose.204,206,207 This may be dose dependent.14

There does not appear to be evidence that any one opioid has less impact than another.208 However, stable doses of sustained-release opioids do not appear to impair driving activity.204,206,209–211

According to Austroads, a person is not fit to hold an unconditional licence if they have an alcohol disorder or other SUD (eg substance dependence, heavy frequent alcohol or other substance use) that is likely to impair safe driving.205,212

The state or territory driver licensing authority may consider a conditional licence. This is subject to periodic review, taking into account the nature of the driving task and information provided by the treating doctor as to whether the following criteria are met:212

  • The person is involved in a treatment program and has been in remission for at least three months
  • There is an absence of cognitive impairments relevant to driving
  • There is absence of end-organ effects that impact on driving

In practice

Each patient should be considered individually and it is ultimately the prescriber’s judgement that determines opioid prescription.207,213–215 Where there are concerns about a patient’s ability to drive (eg high doses of opioids or opioids plus other sedative medication), a formal driving assessment may be considered.

When starting opioid therapy, patients should be advised that they are likely to be impaired and should not drive until a stable regime has been obtained for at least two weeks.

There is moderate, generally consistent evidence that driving performance of patients on long-term opioids for chronic pain may not be negatively affected by their medication.204,211 Driving at night may be a problem due to the persistent miotic effects of opioid drugs reducing peripheral vision.203
 

Sleep-disordered breathing describes a spectrum of disorders, including obstructive sleep apnoea (OSA). One in 15 adults has moderate or more severe OSA, experiencing partial or complete cessation of breathing many times during sleep, and around 80% of those who could benefit from treatment remain undiagnosed.216

Compared to people without OSA, people with OSA are at higher risk of increased sensitivity to opioid analgesia and decreased sensitivity to pain.217 Administration of opioids may also exacerbate OSA.218,219

Experts in this area recommend non-opioid analgesics, and other pain management techniques should be used as either an alternative to opioids or to help limit the amount of opioid required.220–222

In practice

If opioids are prescribed for patients with mild sleep-disordered breathing, careful monitoring and cautious dose titration should be used. Prescribing opioids to patients with moderate or severe sleep-disordered breathing should be avoided whenever possible to minimise risks for opioid overdose.15,223

The use of opioids in patients with severe untreated sleep apnoea is not recommended.54

As the population ages the challenge of safe and appropriate pain management increases. Management challenges include age-related changes in physiology, increased risk of falls,224,225 pharmacodynamics and pharmacokinetics, higher prevalence of comorbidities and concurrent medications, altered responses to pain, and difficulties with assessment of pain severity and response to treatment, including problems related to cognitive impairment.

Consider the use of non-drug strategies such as movement, exercise, physiotherapy and psychological therapies as alternatives to, or in combination with, medication.226 Where opioids are used, consider risk assessment for falls and interventions to mitigate common risks of opioid therapy such as constipation. Also, monitor older patients for the presence of cognitive impairment.15,226

Despite the higher incidence of side effects with drug therapy in older people, analgesics may still be safely and effectively used if tailored for the individual patient and comorbidity and other medications are considered.226 However, analgesics should be:226

  • initiated one at a time using a low dose
  • monitored regularly and adjusted as needed to improve efficacy and limit adverse events • titrated slowly according to response
  • used in combination where synergistic effects provide improved pain relief with fewer side effects than higher doses of a single drug.

When prescribing opioids to older adults, it is important to provide education about risky medication-related behaviours such as obtaining controlled medications from multiple prescribers and saving or stockpiling unused medications.15

Opioid therapy

Appropriate precautions must be taken when considering opioid therapy for older patients.227 These precautions include lower starting doses, slower titration, longer dosing intervals, more frequent monitoring and tapering of benzodiazepines.194,227 There is an increased risk of adverse effects including cognitive impairment, sedation, respiratory depression and falls.228,229 The risk of respiratory depression is minimised by monitoring the patient for sedation and reducing the dose of opioid if this occurs.228

While there are large individual differences, older patients are more sensitive to opioids and dose requirement decreases progressively with age, often reduced by 50% or more. There may be fewer pharmacokinetic differences between older and younger patients with fentanyl,81 morphine, oxycodone230 and buprenorphine.108 However, in the clinical setting, there is evidence of an age-related 2–4-fold decrease in morphine and fentanyl requirements.231,232 In patients older than 75 years, the elimination half-life of tramadol is slightly prolonged233 and lower daily doses have been suggested.234

In practice

Older patients require less opioid medication than younger patients to achieve the same degree of pain relief; harms can also occur at lower doses than they occur in younger patients.231,232,235 However, inter-patient variability exists in all age groups and doses must be titrated to effect in all patients.

  1. 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):1644–56.
  2. The Pharmaceutical Benefits Scheme (PBS) Drug Utilisation Sub-committee (DUSC). Opioid analgesics: Overview. Canberra: Department of Health, 2014 [Accessed 11 July 2017].
  3. Roxburgh A, Ritter A, Slade T, Burns L. Trends in drug use and related harms in Australia, 2001 to 2013. Sydney: National Drug and Alcohol Research Centre, University of New South Wales, 2013.
  4. Degenhardt L, Gisev N, Cama E, et al. The extent and correlates of community-based pharmaceutical opioid utilisation in Australia. Pharmacoepidemiol Drug Saf 2016;25(5):521–38.
  5. Therapeutic Goods Administration. Update on the proposal for the rescheduling of codeine products: Codeine containing medicines to move to prescription only. Canberra: TGA, 2016 [Accessed 20 December 2016].
  6. Rogers KD, Kemp A, McLachlan AJ, Blyth F. Adverse selection? A multi-dimensional profile of people dispensed opioid analgesics for persistent non-cancer pain. PLoS One 2013;8(12):e80095.
  7. Vowles KE, McEntee ML, Julnes PS, et al. Rates of opioid misuse, abuse, and addiction in chronic pain: A systematic review and data synthesis. Pain 2015;156(4):569–76.
  8. Fleming MF, Balousek SL, Klessig CL, Mundt MP, Brown DD. Substance use disorders in a primary care sample receiving daily opioid therapy. J Pain 2007;8(7):573–82.
  9. Chou R, Deyo R, Devine E, et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Rockville, MD: Agency for Healthcare Research and Quality, 2014 ehc/products/557/1971/chronic-pain-opioid-treatmentreport-141007.pdf [Accessed 11 July 2017].
  10. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015;162(4):276–86.
  11. Nielsen S, Bruno R, Degenhardt L, et al. The sources of pharmaceuticals for problematic users of benzodiazepines and prescription opioids. Med J Aust 2013;199(10):696–69.
  12. Australian Institute of Health and Welfare. National hospital morbidity database (NHMD). Canberra: AIHW, 2017 [Accessed 4 September 2017].
  13. Pennington Institute. Australia’s annual overdose report. Melbourne: Pennington Institute, 2016. Available at www. [Accessed 11 July 2017].
  14. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med 2011;171(7):686–91.
  15. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain – United States, 2016. JAMA 2016;315(15):1624–45.
  16. Paulozzi L, Mack K, Jone C. Vital signs: Risk for overdose from methadone used for pain relief — United States, 1999–2010. Atlanta, GA: Centers for Disease Control and Prevention, 2012 mmwrhtml/mm6126a5.htm [Accessed 11 July 2017].
  17. Paulozzi LJ, Xi Y. Recent changes in drug poisoning mortality in the United States by urban–rural status and by drug type. Pharmacoepidemiol Drug Saf 2008;17(10):997–1005.
  18. Coroners Court of Victoria. Submission to the Inquiry into Drug Law Reform: Coronial recommendations on drug harm reduction. Melbourne: Coroners Court of Victoria, 2017.
  19. Sproule B. Prescription monitoring programs in Canada: Best practice and program review. Ottawa, ON: Canadian Centre on Substance Abuse, 2015 Resource Library/CCSA-Prescription-Monitoring-Programs-inCanada-Report-2015-en.pdf [Accessed 29 September 2016].
  20. Brady JE, Wunsch H, DiMaggio C, et al. Prescription drug monitoring and dispensing of prescription opioids. Public Health Rep 2014;129(2):139–47.
  21. Paulozzi LJ, Kilbourne EM, Desai HA. Prescription drug monitoring programs and death rates from drug overdose. Pain Med 2011;12(5):747–54.
  22. Li G, Brady JE, Lang BH, et al. Prescription drug monitoring and drug overdose mortality. Injury Epidemiology 2014;1(1):1–8.
  23. Goodin A, Blumenschein K, Freeman PR, Talbert J. Consumer/patient encounters with prescription drug monitoring programs: Evidence from a Medicaid population. Pain Physician 2012;15(3 Suppl):ES169–75.
  24. Islam MM, McRae IS. An inevitable wave of prescription drug monitoring programs in the context of prescription opioids: Pros, cons and tensions. BMC Pharmacol Toxicol 2014;15:46.
  25. Clark T, Eadie J, Knue P, Kreiner P, Strickler G. Prescription drug monitoring programs: An assessment of the evidence for best practices: The Prescription Drug Monitoring Program Center of Excellence, 2012.
  26. Ogeil RP, Heilbronn C, Lloyd B, Lubman DI. Prescription drug monitoring in Australia: Capacity and coverage issues. Med J Aust 2016;204(4):148.
  27. Sabanovic H, Harris B, Clavisi O, Bywaters L. Attitudes towards opioids among patients prescribed medication in Victoria. Melbourne: Move Muscle, Bone & Joint Health, 2016 MOVE-Opioid-study.aspx [Accessed 19 February 2017].
  28. Harris S, Taylor S, National Treatment Agency. Clinical governance in drug treatment: A good practice guide for providers and commissioners. London: NHS National Treatment Agency for Substance Misuse, 2009 [Accessed 11 July 2017].
  29. Chewning B, Bylund CL, Shah B, et al. Patient preferences for shared decisions: A systematic review. Patient Educ Couns 2012;86(1):9–18.
  30. The Royal Australian College of General Practitioners. Standards for general practices. 4th edn. Melbourne: RACGP, 2013.
  31. Coulter A, Collins A. Making shared decision-making a reality: No decision about me, without me. London: The King’s Fund, 2011.
  32. O’Shea E. Quality in Practice Committee: Communicating risk to patients. Dublin: Irish College of General Practitioners, 2014.
  33. Hoffmann TC, Montori VM, Del Mar C. The connection between evidence-based medicine and shared decision making. JAMA 2014;312(13):1295–96.
  34. Stacey D, Bennett CL, Barry MJ, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2011(10):CD001431.
  35. Hoffmann TC, Legare F, Simmons MB, et al. Shared decision making: What do clinicians need to know and why should they bother? Med J Aust 2014;201(1):35–39.
  36. Ahmed H, Naik G, Willoughby H, Edwards AG. Communicating risk. BMJ 2012;344:e3996.
  37. Patient Safety and Quality Improvement Service. Guide to informed decision-making in healthcare. Brisbane: Queensland Health, 2012.
  38. Clayman ML, Bylund CL, Chewning B, Makoul G. The impact of patient participation in health decisions within medical encounters: A systematic review. Med Decis Making 2016;36(4):427–52.
  39. Shay LA, Lafata JE. Where is the evidence? A systematic review of shared decision making and patient outcomes. Med Decis Making 2015;35(1):114–31.
  40. Thompson-Leduc P, Clayman ML, Turcotte S, Legare F. Shared decision-making behaviours in health professionals: A systematic review of studies based on the Theory of Planned Behaviour. Health Expect 2015;18(5):754-74.
  41. Legare F, Stacey D, Turcotte S, et al. Interventions for improving the adoption of shared decision making by healthcare professionals. Cochrane Database Syst Rev 2014;9:Cd006732.
  42. Hoffmann TC, Del Mar C. Patients’ expectations of the benefits and harms of treatments, screening, and tests: A systematic review. JAMA Intern Med 2015;175(2):274–86.
  43. Frei M. Opioid dependence: Management in general practice. Aust Fam Physician 2010;39(8):548–52.
  44. National Institute on Drug Abuse. Prescription drugs: Abuse and addiction. Rev edn. Bethesda, MD: NIDA, 2011.
  45. Gowing L, Ali R, Dunlop A, Farrell M, Lintzeris N. National guidelines for medication-assisted treatment of opioid dependence. Canberra: Commonwealth of Australia, 2014 CA257CD1001E0E5D/$File/National_Guidelines_2014.pdf [Accessed 11 July 2017].
  46. Heit H, Lipman A. Pain: Substance abuse issue in the treatment of pain. In: Moore R, editor. Biobehavioral approaches to pain. New York: Springer Science+Business Media, LLC, 2009.
  47. Arizona Department of Health Services. Arizona opioid prescribing guidelines: A voluntary, consensus set of guidelines that promotes best practices for prescribing opioids for acute and chronic pain. Phoenix, AZ: Arizona Department of Health, 2014. Available at http://azdhs. gov/documents/audiences/clinicians/clinical-guidelinesrecommendations/prescribing-guidelines/az-opiodprescribing-guidelines.pdf [Accessed 11 July 2017].
  48. Schug SA, Palmer GM, Scott DA, Halliwell R, Trinca J, editors. Acute pain management: Scientific evidence. 4th edn. Melbourne: Australia and New Zealand College of Anaesthetists and Faculty of Pain Medicine, 2015 [Accessed 11 July 2017].
  49. Sehgal N, Manchikanti L, Smith HS. Prescription opioid abuse in chronic pain: A review of opioid abuse predictors and strategies to curb opioid abuse. Pain Physician 2012;15(3 Suppl):ES67–92.
  50. Gordon A, Cone EJ, DePriest AZ, Axford-Gatley RA, Passik SD. Prescribing opioids for chronic noncancer pain in primary care: Risk assessment. Postgrad Med 2014;126(5):159–66.
  51. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ 2015;350:g6380.
  52. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Recommendations regarding the use of opioid analgesics in patients with chronic noncancer pain. Melbourne: ANZCA and FPM, 2015 [Accessed 11 July 2017].
  53. Australian and New Zealand College of Anaesthetists. Guidelines on acute pain management. Melbourne: ANZCA, 2013 Documents/ps41-2013-guidelines-on-acute-painmanagement [Accessed 11 July 2017].
  54. Hughes MA, Biggs JJ, Theise MS, et al. Recommended opioid prescribing practices for use in chronic non-malignant pain: A systematic review of treatment guidelines. J Manag Care Med 2011;14(3):52.
  55. Kahan M, Mailis-Gagnon A, Wilson L, Srivastava A, National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic noncancer pain: Clinical summary for family physicians. Part 1: general population. Can Fam Physician 2011;57(11):1257-66, e407–18.
  56. Drug and Alcohol Services South Australia. Opioid prescription in chronic pain conditions. Adelaide: DAAS SA, Flinders Medical Centre Pain Management Unit, Royal Adelaide Hospital Pain Management Unit, 2008.
  57. Huxtable CA, Roberts LJ, Somogyi AA, MacIntyre PE. Acute pain management in opioid-tolerant patients: A growing challenge. Anaesth Intensive Care 2011;39(5):804–23.
  58. Quinlan J, Carter K. Acute pain management in patients with persistent pain. Curr Opin Support Palliat Care 2012;6(2):188–93.
  59. Schug SA. Acute pain management in the opioid-tolerant patient. Pain Manag 2012;2(6):581–91.
  60. Lyapustina T, Castillo R, Omaki E, et al. The contribution of the emergency department to opioid pain reliever misuse and diversion: A critical review. Pain Pract 2017. doi: 10.1111/ papr.12568.
  61. Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376(7):663–73.
  62. Macintyre PE, Huxtable CA, Flint SL, Dobbin MD. Costs and consequences: A review of discharge opioid prescribing for ongoing management of acute pain. Anaesth Intensive Care 2014;42(5):558–74.
  63. 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(3):273–79.
  64. Lewis ET, Cucciare MA, Trafton JA. What do patients do with unused opioid medications? Clin J Pain 2014;30(8):654–62.
  65. Thorson D, Biewen P, Bonte B, et al. Acute pain assessment and opioid prescribing protocol. Bloomington, MN: Institute for Clinical Systems Improvement, 2014 [Accessed 11 July 2017].
  66. Harris K, Curtis J, Larsen B, et al. Opioid pain medication use after dermatologic surgery: A prospective observational study of 212 dermatologic surgery patients. JAMA Dermatol 2013;149(3):317–21.
  67. 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(2):551–55.
  68. Rodgers J, Cunningham K, Fitzgerald K, Finnerty E. Opioid consumption following outpatient upper extremity surgery. J Hand Surg Am 2012;37(4):645–50.
  69. Platis A, Wenzel T. Hospital oxycodone utilisation research study (HOURS). Adelaide: Pharmacy Department Royal Adelaide Hospital, 2011.
  70. Alam A, Gomes T, Zheng H, et al. Long-term analgesic use after low-risk surgery: A retrospective cohort study. Arch Intern Med 2012;172(5):425–30.
  71. Carroll I, Barelka P, Wang CK, et al. A pilot cohort study of the determinants of longitudinal opioid use after surgery. Anesth Analg 2012;115(3):694–702.
  72. Clarke H, Soneji N, Ko DT, Yun L, Wijeysundera DN. Rates and risk factors for prolonged opioid use after major surgery: population based cohort study. BMJ 2014;348:g1251.
  73. Hunter New England Local Health District. Reconsidering opioid therapy: NSW Government, 2014 opioid_therapy_May 2014.pdf [Accessed 12 July 2017].
  74. Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF. Opioid prescribing after nonfatal overdose and association with repeated overdose: A cohort study. Ann Intern Med 2016;164(1):1–9.
  75. Bazazi AR, Zaller ND, Fu JJ, Rich JD. Preventing opiate overdose deaths: Examining objections to takehome naloxone. J Health Care Poor Underserved 2010;21(4):1108–13.
  76. MacIntyre PE, Scott DA, Scott SA, Visser EJ, Walker SM, editors. Acute pain management: Scientific evidence. 3rd edn. Melbourne: Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine, 2010.
  77. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: Evidence and recommendations for everyday practice. Mayo Clin Proc 2015;90(6):828–42.
  78. Corbett AD, Henderson G, McKnight AT, Paterson SJ. 75 years of opioid research: The exciting but vain quest for the Holy Grail. Br J Pharmacol 2006;147 Suppl 1:S153–62.
  79. Dahan A, Kest B, Waxman AR, Sarton E. Sex-specific responses to opiates: Animal and human studies. Anesth Analg 2008;107(1):83–95.
  80. Campesi I, Fois M, Franconi F. Sex and gender aspects in anesthetics and pain medication. Handb Exp Pharmacol 2012(214):265–78.
  81. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987;240(1):159–66.
  82. Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997;86(1):10–23.
  83. Macintyre P, Upton R. Acute pain management in the elderly patient. In: Macintyre P, Walker S, Rowbotham D, editors. Clinical pain management: Acute pain. 2nd edn. London: Hodder Arnold, 2008.
  84. Hurley RW, Adams MC. Sex, gender, and pain: An overview of a complex field. Anesth Analg 2008;107(1):309–17.
  85. Lee CW, Ho IK. Sex differences in opioid analgesia and addiction: Interactions among opioid receptors and estrogen receptors. Mol Pain 2013;9:45.
  86. Svetlik S, Hronova K, Bakhouche H, Matouskova O, Slanar O. Pharmacogenetics of chronic pain and its treatment. Mediators Inflamm 2013;2013:864319.
  87. Xu Y, Johnson A. Opioid therapy pharmacogenomics for noncancer pain: Efficacy, adverse events, and costs. Pain Res Treat 2013;2013. doi:10.1155/2103/864319.
  88. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther 2007;81(3):429–44.
  89. Yang Z, Yang Z, Arheart KL, et al. CYP2D6 poor metabolizer genotype and smoking predict severe postoperative pain in female patients on arrival to the recovery room. Pain Med 2012;13(4):604–09.
  90. Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012;129(5):e1343–47.
  91. Kirchheiner J, Schmidt H, Tzvetkov M, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 2007;7(4):257–65.
  92. Friedrichsdorf SJ, Nugent AP, Strobl AQ. Codeineassociated pediatric deaths despite using recommended dosing guidelines: Three case reports. J Opioid Manag 2013;9(2):151–55.
  93. Stamer UM, Stuber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 2008;107(3):926–69.
  94. Stamer UM, Stuber F. Genetic factors in pain and its treatment. Curr Opin Anaesthesiol 2007;20(5):478–84.
  95. Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid analgesia. Pharmgenomics Pers Med 2012;5:73–87.
  96. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95(4):376–82.
  97. Holmquist G. Opioid metabolism and effects of cytochrome P450. Pain Med 2009;10(S1):S20–29.
  98. Smith HS. Opioid metabolism. Mayo Clin Proc 2009;84(7):613–24.
  99. Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 2009;41(2):89–295.
  100. Stamer UM, Stuber F. The pharmacogenetics of analgesia. Expert Opin Pharmacother 2007;8(14):2235–45.
  101. Manchikanti L, Ailinani H, Koyyalagunta D, et al. A systematic review of randomized trials of long-term opioid management for chronic non-cancer pain. Pain Physician 2011;14(2):91–121.
  102. Karlsson M, Berggren AC. Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: A 12-week, randomized, open-label, controlled, parallel-group noninferiority study. Clin Ther 2009;31(3):503–13.
  103. Licina L, Hamsher C, Lautenschager K, et al. Buprenorphine/naloxone therapy for opioid refractory neuropathic pain following traumatic amputation: A case series. Mil Med 2013;178(7):e858–61.
  104. Simpson RW, Wlodarczyk JH. Transdermal buprenorphine relieves neuropathic pain: A randomized, double-blind, parallel-group, placebo-controlled trial in diabetic peripheral neuropathic pain. Diabetes Care 2016;39(9):1493–500.
  105. Guetti C, Angeletti C, Marinangeli F, et al. Transdermal buprenorphine for central neuropathic pain: Clinical reports. Pain Pract 2011;11(5):446–52.
  106. Wiffen PJ, Derry S, Moore RA, et al. Buprenorphine for neuropathic pain in adults. Cochrane Database Syst Rev 2015(9):CD011603.
  107. Pergolizzi J, Aloisi AM, Dahan A, et al. Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract 2010;10(5):428–50.
  108. Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain 2009;13(3):219–30.
  109. Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth 2006;96(5):627–32.
  110. Boom M, Niesters M, Sarton E, et al. Non-analgesic effects of opioids: Opioid-induced respiratory depression. Curr Pharm Des 2012;18(37):5994–6004.
  111. Hunter Integrated Pain Service. Health professional resources: Opioid selection. Newcastle, NSW: Hunter New England Health, 2013 au/__data/assets/pdf_file/0003/212961/Opioid_Selection. pdf [Accessed 12 July 2017].
  112. Lotsch J. Opioid metabolites. J Pain Symptom Manage 2005;29(5 Suppl):S10–24.
  113. Shaheed CA, Maher CG, McLachlan AJ. Investigating the efficacy and safety of over-the-counter codeine containing combination analgesics for pain and codeine based antitussives. Canberra: Therapeutic Goods Association, 2016 [Accessed 12 July 2017].
  114. Derry S, Moore RA, McQuay HJ. Single dose oral codeine, as a single agent, for acute postoperative pain in adults. Cochrane Database Syst Rev 2010(4):CD008099.
  115. Derry S, Karlin SM, Moore RA. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database Syst Rev 2015;2:CD010107.
  116. Buckley NA, Faunce TA. Trials and tribulations in the removal of dextropropoxyphene from the Australian Register of Therapeutic Goods. Med J Aust 2013;199(4):257–60.
  117. Collins SL, Edwards JE, Moore RA, McQuay HJ. Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain. Cochrane Database Syst Rev 2000(2):CD001440.
  118. Li Wan Po A, Zhang WY. Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol. BMJ 1997;315(7122):1565–71.
  119. Grape S, Schug SA, Lauer S, Schug BS. Formulations of fentanyl for the management of pain. Drugs 2010;70(1):57–72.
  120. Quigley C. Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev 2002(1):CD003447.
  121. Felden L, Walter C, Harder S, et al. Comparative clinical effects of hydromorphone and morphine: A meta-analysis. Br J Anaesth 2011;107(3):319–28.
  122. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005;19(4):13–24.
  123. Weschules DJ, Bain KT, Richeimer S. Actual and potential drug interactions associated with methadone. Pain Med 2008;9(3):315–44.
  124. Fredheim OM, Moksnes K, Borchgrevink PC, Kaasa S, Dale O. Clinical pharmacology of methadone for pain. Acta Anaesthesiol Scand 2008;52(7):879–89.
  125. Weschules DJ, Bain KT. A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Pain Med 2008;9(5):595–612.
  126. Klimas R, Mikus G. Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: A quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide. Br J Anaesth 2014;113(6):935–44.
  127. Faura CC, Collins SL, Moore RA, McQuay HJ. Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain 1998;74(1):43–53.
  128. Klepstad P, Dale O, Kaasa S, et al. Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: A prospective survey in 300 adult cancer patients. Acta Anaesthesiol Scand 2003;47(6):725–31.
  129. Vallejo R, de Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: A review. Am J Ther 2004;11(5):354–65.
  130. Budd K. Pain management: Is opioid immunosuppression a clinical problem? Biomed Pharmacother 2006;60(7):310–17.
  131. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and metaanalysis. Lancet Neurol 2015;14(2):162–73.
  132. Lalovic B, Kharasch E, Hoffer C, et al. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther 2006;79(5):461–79.
  133. Samer CF, Daali Y, Wagner M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol 2010;160(4):919–30.
  134. Zwisler ST, Enggaard TP, Mikkelsen S, Brosen K, Sindrup SH. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand 2010;54(2):232–40.
  135. Kokki H, Kokki M, Sjovall S. Oxycodone for the treatment of postoperative pain. Expert Opin Pharmacother 2012;13(7):1045–58.
  136. Olkkola KT, Kontinen VK, Saari TI, Kalso EA. Does the pharmacology of oxycodone justify its increasing use as an analgesic? Trends Pharmacol Sci 2013;34(4):206–14.
  137. DePriest AZ, Miller K. Oxycodone/naloxone: Role in chronic pain management, opioid-induced constipation, and abuse deterrence. Pain Ther 2014;3(1):1–15.
  138. Nieminen TH, Hagelberg NM, Saari TI, et al. St John’s wort greatly reduces the concentrations of oral oxycodone. Eur J Pain 2010;14(8):854–59.
  139. Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS. Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. Arch Surg 2002;137(1):84–88.
  140. Silverman ME, Shih RD, Allegra J. Morphine induces less nausea than meperidine when administered parenterally. J Emerg Med 2004;27(3):241–43.
  141. Latta KS, Ginsberg B, Barkin RL. Meperidine: A critical review. Am J Ther 2002;9(1):53–68.
  142. Benner KW, Durham SH. Meperidine restriction in a pediatric hospital. J Pediatr Pharmacol Ther 2011;16(3):185–90.
  143. Tzschentke TM, Christoph T, Kogel BY. The mu opioid receptor agonist/noradrenaline reuptake inhibition (MORNRI) concept in analgesia: The case of tapentadol. CNS Drugs 2014;28(4):319–29.
  144. Vinik AI, Shapiro DY, Rauschkolb C, et al. A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy. Diabetes Care 2014;37(8):2302–09.
  145. Raffa RB, Buschmann H, Christoph T, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother 2012;13(10):1437–49.
  146. Riemsma R, Forbes C, Harker J, et al. Systematic review of tapentadol in chronic severe pain. Curr Med Res Opin 2011;27(10):1907–30.
  147. Biondi DM, Xiang J, Etropolski M, Moskovitz B. Evaluation of blood pressure and heart rate in patients with hypertension who received tapentadol extended release for chronic pain: A post hoc, pooled data analysis. Clin Drug Investig 2014;34(8):565–76.
  148. Xu XS, Smit JW, Lin R, et al. Population pharmacokinetics of tapentadol immediate release (IR) in healthy subjects and patients with moderate or severe pain. Clin Pharmacokinet 2010;49(10):671–82.
  149. Kemp W, Schlueter S, Smalley E. Death due to apparent intravenous injection of tapentadol. J Forensic Sci 2013;58(1):288–91.
  150. Dart RC, Cicero TJ, Surratt HL, et al. Assessment of the abuse of tapentadol immediate release: The first 24 months. J Opioid Manag 2012;8(6):395–402.
  151. Cepeda MS, Fife D, Ma Q, Ryan PB. Comparison of the risks of opioid abuse or dependence between tapentadol and oxycodone: Results from a cohort study. J Pain 2013;14(10):1227–41.
  152. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database Syst Rev 2015;9:CD011460.
  153. Afilalo M, Etropolski MS, Kuperwasser B, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: A randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig 2010;30(8):489–505.
  154. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: Results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. Expert Opin Pharmacother 2010;11(11):1787–804.
  155. Lee YK, Ko JS, Rhim HY, et al. Acute postoperative pain relief with immediate-release tapentadol: Randomized, double-blind, placebo-controlled study conducted in South Korea. Curr Med Res Opin 2014;30(12):2561–70.
  156. Lange B, Kuperwasser B, Okamoto A, et al. Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther 2010;27(6):381–99.
  157. Niesters M, Proto PL, Aarts L, et al. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth 2014;113(1):148–56.
  158. Raffa RB, Friderichs E, Reimann W, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992;260(1):275–85.
  159. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993;46(2):313–40.
  160. Stamer UM, Lehnen K, Hothker F, et al. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 2003;105(1–2):231–38.
  161. Radbruch L, Grond S, Lehmann KA. A risk–benefit assessment of tramadol in the management of pain. Drug Saf 1996;15(1):8–29.
  162. Lim A, Schug S. Tramadol versus morphine as oral stepdown analgesia after postoperative epidural analgesia. Reg Anesth Pain Med 2001;26(2):S133.
  163. Wilder-Smith CH, Hill L, Wilkins J, Denny L. Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. Anesthesiology 1999;91(3):639–47.
  164. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and oxycodone. J Clin Anesth 1997;9(7):582–85.
  165. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and pethidine. Eur J Anaesthesiol 1998;15(1):64–8.
  166. Jick H, Derby LE, Vasilakis C, Fife D. The risk of seizures associated with tramadol. Pharmacotherapy 1998;18(3):607–11.
  167. Gasse C, Derby L, Vasilakis-Scaramozza C, Jick H. Incidence of first-time idiopathic seizures in users of tramadol. Pharmacotherapy 2000;20(6):629–34.
  168. Nelson EM, Philbrick AM. Avoiding serotonin syndrome: The nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother 2012;46(12):1712–16.
  169. Radbruch L, Glaeske G, Grond S, et al. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany. Subst Abus 2013;34(3):313–20.
  170. Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: A randomized, double-blind, placebocontrolled trial. Clin J Pain 2009;25(3):177–84.
  171. Australian medicines handbook 2015. Adelaide: Australian Medicines Handbook Pty Ltd, 2015. Available at http:// [Accessed 12 July 2017].
  172. McQuay HJ. Opioid clinical pharmacology and routes of administration. Br Med Bull 1991;47(3):703–17.
  173. Gammaitoni AR, Fine P, Alvarez N, McPherson ML, Bergmark S. Clinical application of opioid equianalgesic data. Clin J Pain 2003;19(5):286–97.
  174. 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(3 Suppl):S67–116.
  175. American Academy of Pain Medicine, American Pain Society, American Society of Addiction Medicine. Public policy statement on the rights and responsibilities of health care professionals in the use of opioids for the treatment of pain: A consensus document from the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine. Pain Med 2004;5(3):301–02.
  176. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 2011;14(2):145–61.
  177. Low Y, Clarke CF, Huh BK. Opioid-induced hyperalgesia: A review of epidemiology, mechanisms and management. Singapore Med J 2012;53(5):357–60.
  178. Chang G, Chen L, Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am 2007;91(2):199–211.
  179. Mao J. Opioid-induced hyperalgesia. Washington, DC: International Association for the Study of Pain, 2008 [Accessed 12 July 2017].
  180. Joo DT. Mechanisms of opioid tolerance: Merging evidence and therapeutic implications. Can J Anaesth 2007;54(12):969–76.
  181. Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: Molecular mechanisms and clinical considerations. Clin J Pain 2008;24(6):479–96.
  182. Reznikov I, Pud D, Eisenberg E. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain. Br J Clin Pharmacol 2005;60(3):311–18.
  183. Ahmedzai SH, Boland J. Constipation in people prescribed opioids. BMJ Clin Evid 2006;12:2407.
  184. Rosow CE, Gomery P, Chen TY, et al. Reversal of opioidinduced bladder dysfunction by intravenous naloxone and methylnaltrexone. Clin Pharmacol Ther 2007;82(1):48–53.
  185. Kjellberg F, Tramer MR. Pharmacological control of opioidinduced pruritus: A quantitative systematic review of randomized trials. Eur J Anaesthesiol 2001;18(6):346–57.
  186. Mujtaba S, Romero J, Taub CC. Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale? J Cardiovasc Dis Res 2013;4(4):229–35.
  187. Fanoe S, Jensen GB, Sjogren P, Korsgaard MP, Grunnet M. Oxycodone is as
This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log

Advertising