Opioid-induced bowel dysfunction in cancer-related pain: Causes, consequences, and a novel approach for its management

Authors

  • Peter Holzer, PhD
  • Sam H. Ahmedzai, BSc, MBChB, FRCP
  • Norbert Niederle, MD
  • Petra Leyendecker, PhD
  • Michael Hopp, MD
  • Björn Bosse, Statistics (Diploma)
  • Ingrid Spohr, PhD
  • Karen Reimer, MD

DOI:

https://doi.org/10.5055/jom.2009.0015

Keywords:

cancer, constipation, naloxone, opioid, oxycodone, pain

Abstract

Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient’s morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone provided effective analgesia with improved bowel function in patients suffering from severe cancer-related and noncancer-related pain. The combination has the potential to improve the quality of pain management significantly in these patients.

Author Biographies

Peter Holzer, PhD

Institut für Experimentelle und Klinische Pharmakologie, Medizinische Universität Graz, Graz, Austria.

Sam H. Ahmedzai, BSc, MBChB, FRCP

Academic Unit of Supportive Care, Section of Oncology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.

Norbert Niederle, MD

Klinikum Leverkusen GmbH, Medizinische Klinik III, Leverkusen, Germany.

Petra Leyendecker, PhD

Mundipharma Research GmbH & Co. KG, Limburg (Lahn), Germany.

Michael Hopp, MD

Mundipharma Research GmbH & Co. KG, Limburg (Lahn), Germany.

Björn Bosse, Statistics (Diploma)

Mundipharma Research GmbH & Co. KG, Limburg (Lahn), Germany.

Ingrid Spohr, PhD

Mundipharma GmbH, Limburg (Lahn), Germany.

Karen Reimer, MD

Mundipharma Research GmbH & Co. KG, Limburg (Lahn), Germany; University Witten/Herdecke, Witten, Germany.

References

Ballantyne JC: Opioid analgesia: Perspectives on right use and utility. Pain Physician. 2007; 10: 479-491.

Coluzzi F, Pappagallo M: Opioid therapy for chronic noncancer pain: Practice guidelines for initiation and maintenance of therapy. Minerva Anestesiol. 2005; 71: 425-433.

Choi YS, Billings JA: Opioid antagonists: A review of their role in palliative care, focusing on use in opioid-related constipation. J Pain Symptom Manage. 2002; 24: 71-90.

Kurz A, Sessler DI: Opioid-induced bowel dysfunction: Pathophysiology and potential new therapies. Drugs. 2003; 63: 649-671.

European Pain in Cancer (EPIC) Survey: Available at http://www.paineurope.com. Accessed November 2007.

Colvin L, Forbes K, Fallon M: Difficult pain. Br Med J (Clin Res Ed). 2006; 332: 1081-1083.

Pappagallo M: Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001; 182: 11S-18S.

Fitzgibbon DR: Clinical use of opioids for cancer pain. Curr Pain Headache Rep. 2007; 11: 251-258.

Coluzzi F, Mattia C: Oxycodone. Pharmacological profile and clinical data in chronic pain management. Minerva Anestesiol. 2005; 71: 451-460.

Gallego AO, Barón MG, Arranz EE: Oxycodone: A pharmacological and clinical review. Clin Transl Oncol. 2007; 9: 298-307.

Ross FB, Smith MT: The intrinsic antinociceptive effects of oxycodone appear to be [kappa]-opioid receptor mediated. Pain. 1997; 73: 151-157.

Bruera E, Belzile M, Pituskin E, et al.: Randomized, doubleblind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. J Clin Oncol. 1998; 16: 3222-3229.

Mucci-LoRusso P, Berman BS, Silberstein PT, et al.: Controlledrelease oxycodone compared with controlled-release morphine in the treatment of cancer pain: A randomized, double-blind, parallel-group study. Eur J Pain. 1998; 2: 239-249.

Lauretti GR, Oliveira GM, Pereira NL: Comparison of sustained-release morphine with sustained release oxycodone in advanced cancer patients. Br J Cancer. 2003; 89: 2027-2030.

Hale ME, Fleischmann R, Salzman R, et al.: Efficacy and safety of controlled-release versus immediate-release oxycodone: Randomized, double-blind evaluation in patients with chronic back pain. Clin J Pain 1999; 15: 179-183.

Gimbel JS, Richards P, Portenoy RK: Controlled-release oxycodone for pain in diabetic neuropathy: A randomized controlled trial. Neurology. 2003; 60: 927-934.

Kampe S, Warm M, Kaufmann J, et al.: Clinical efficacy of controlled-release oxycodone 20 mg administered on a 12-h dosing schedule on the management of postoperative pain after breast surgery for cancer. Curr Med Res Opin. 2004; 20: 199-202.

Watson CP, Moulin D, Watt-Watson J, et al.: Controlledrelease oxycodone relieves neuropathic pain: A randomized controlled trial in painful diabetic neuropathy. Pain. 2003; 105: 71-78.

Watson CP, Babul N: Efficacy of oxycodone in neuropathic pain: A randomized trial in postherpetic neuralgia. Neurology. 1998; 50: 1837-1841.

Reid CM, Martin RM, Sterne JA, et al.: Oxycodone for cancerrelated pain: Meta-analysis of randomized controlled trials. Archiv Intern Med. 2006; 166: 837-843.

Davis MP: The opioid bowel syndrome: A review of pathophysiology and treatment. J Opioid Manag. 2005; 1: 153-161.

Holzer P: Opioids and opioid receptors in the enteric nervous system: From a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett. 2004; 361: 192-195.

De Luca A, Coupar IM: Insights into opioid action in the intestinal tract. Pharmacol Ther. 1996; 69: 103-115.

McMillan SC: Assessing and managing opiate-induced constipation in adults with cancer. Cancer Control. 2004; 11: 3-9.

Bell T, Milanova T, Grove G, et al.: Obd symptoms impair quality of life and daily activities, regardless of frequency and duration of opioid treatment: Results of a us patient survey (probe survey). J Pain. 2007; 8: S71 (Abstract 882).

Ueberall MA, Mueller-Schwefe G: Opioid-induced constipation–A frequent and distressing side effect in daily practice affecting oral and transdermal opioid applications. Eur J Pain. 2006; 10: S172.

Moulin DE, Iezzi A, Amireh R, et al.: Randomised trial of oral morphine for chronic non-cancer pain. Lancet. 1996; 347: 143-147.

Allan L, Hays H, Jensen N-H, et al.: Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer. Br Med J (Clin Res Ed). 2001; 322: 1154-1158.

Cook S, Bell T, Sweeney C, et al.: Impact on quality of life of constipation-associated gi symptoms related to opioid treatment in chronic pain patients: Pac-qol results from the opioid survey. J Pain. 2007; 8: S71 (Abstract 883).

Annunziata K, Bell T: Impact of opioid-induced constipation on healthcare resource utilisation and patient functioning. Eur J Pain. 2006; 10: S172 (Abstract 659).

Bell T, Annunziata K, Freedman D, et al.: Opioid-induced constipation increases healthcare resource use and impairs work productivity: Comparison with other patient groups with and without constipation. J Pain. 2007; 8: S75 (Abstract 897).

Ahmedzai SH, Boland J: Constipation in people prescribed opioids. BMJ Clin Evid. 2007; 12: 2407.

Sykes NP: The relationship between opioid use and laxative use in terminally ill cancer patients. Palliat Med. 1998; 12: 375-382.

Meissner W, Schmidt U, Hartmann M, et al.: Oral naloxone reverses opioid-associated constipation. Pain. 2000; 84: 105-109.

Liu M, Wittbrodt E: Low-dose oral naloxone reverses opioidinduced constipation and analgesia. J Pain Symptom Manage. 2002; 23: 48-53.

Sykes NP: An investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer. Palliat Med. 1996; 10: 135-144.

Yuan CS, Foss JF, O’Connor M, et al.: Methylnaltrexone for reversal of constipation due to chronic methadone use: A randomized controlled trial. JAMA. 2000; 283: 367-372.

Yuan CS, Wei G, Foss JF, et al.: Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: A double-blind randomized placebo-controlled trial. J Pharmacol Exp Ther. 2002; 300: 118-123.

Paulson DM, Kennedy DT, Donovick RA, et al.: Alvimopan: An oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction–a 21-day treatment-randomized clinical trial. J Pain. 2005; 6: 184-192.

Portenoy RK, Thomas J, Moehl Boatwright ML, et al.: Subcutaneous methylnaltrexone for the treatment of opioidinduced constipation in patients with advanced illness: A doubleblind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage. 2008; 35: 458-468.

Thomas J, Karver S, Cooney GA, et al.: Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008; 358: 2332-2343.

US Food and Drug Administration: FDA approves Entereg to help restore bowel function following surgery. Available at http://www.fda.gov/bbs/topics/NEWS/2008/NEW01838.html. Accessed November 20, 2008.

Saad RJ, Chey WD: Recent developments in the therapy of irritable bowel syndrome. Expert Opin Investig Drugs. 2008; 17: 117-130.

De Schepper HU, Cremonini F, Park MI, et al.: Opioids and the gut: Pharmacology and current clinical experience. Neurogastroenterol Motil. 2004; 16: 383-394.

Meissner W, Leyendecker P, Mueller-Lissner S, et al.: A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain. 2009; 13: 56-64.

Nadstawek J, Leyendecker P, Hopp M, et al.: Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. Int J Clin Pract. 2008; 62: 1159-1167.

Vondrackova D, Leyendecker P, Meissner W, et al.: Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain. J Pain. 2008; 9: 1144-1154.

Thompson WG, Longstreth GF, Drossman DA, et al.: Functional bowel disorders and functional abdominal pain. Gut. 1999; 45 (Suppl 2): 1143-1147.

Published

01/29/2018

How to Cite

Holzer, PhD, P., S. H. Ahmedzai, BSc, MBChB, FRCP, N. Niederle, MD, P. Leyendecker, PhD, M. Hopp, MD, B. Bosse, Statistics (Diploma), I. Spohr, PhD, and K. Reimer, MD. “Opioid-Induced Bowel Dysfunction in Cancer-Related Pain: Causes, Consequences, and a Novel Approach for Its Management”. Journal of Opioid Management, vol. 5, no. 3, Jan. 2018, pp. 145-51, doi:10.5055/jom.2009.0015.

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