Skip to main content

Advertisement

SpringerLink
Log in

New Options in Constipation Management

  • Palliative Medicine (A Jatoi, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes, exercise, and laxatives. However, responses to self-management efforts are often inadequate to relieve the subjective and objective experience of constipation. Multiple new anti-constipating medications have recently been tested in randomized trials and the following are available commercially: probiotics, prucalopride, lubiprostone, linaclotide, elobixibat, antidepressants, methylnaltrexone, alvimopan, and naloxegol. This review will discuss the evidence-based benefits of these medications and outline an approach to managing constipation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Drossman DA. Characterization of intestinal function and diagnosis of irritable bowel syndrome by surveys and questionnaires. Gastroenterol Clin Biol. 1990;14:37C–41.

    CAS  PubMed  Google Scholar 

  2. Whitehead WE, Corazziari E, Prizont R, Senior JR, Thompson WG, Veldhuyzen Van Zanten SJ. Definition of a responder in clinical trials for functional gastrointestinal disorders: report on a symposium. Gut. 1999;45 Suppl 2:II78–9.

    PubMed Central  PubMed  Google Scholar 

  3. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45 Suppl 2:II43–7.

    PubMed Central  PubMed  Google Scholar 

  4. Ford AC, Bercik P, Morgan DG, Bolino C, Pintos-Sanchez MI, Moayyedi P. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology. 2013;145(1262–1270):e1261.

    Google Scholar 

  5. Markland AD, Palsson O, Goode PS, Burgio KL, Busby-Whitehead J, Whitehead WE. Association of low dietary intake of fiber and liquids with constipation: evidence from the National Health and Nutrition Examination Survey. Am J Gastroenterol. 2013;108:796–803.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lembo A, Camilleri M. Chronic constipation. N Engl J Med. 2003;349:1360–8.

    Article  CAS  PubMed  Google Scholar 

  7. Mehra G, Weekes A, Vantrappen P, Visvanathan D, Jeyarajah A. Laparoscopic assisted radical vaginal hysterectomy for cervical carcinoma: morbidity and long-term follow-up. Eur J Surg Oncol. 2010;36:304–8.

    Article  CAS  PubMed  Google Scholar 

  8. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–91.

    Article  PubMed  Google Scholar 

  9. Nullens S, Nelsen T, Camilleri M, Burton D, Eckert D, Iturrino J, et al. Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation. Gut. 2012;61:1132–9.

    Article  PubMed  Google Scholar 

  10. Song KH. Practical methods to assess chronic constipation. J Neurogastroenterol Motil. 2015;21:307–8.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Bellini M, Gambaccini D, Salvadori S, Tosetti C, Urbano MT, Costa F, et al. Management of chronic constipation in general practice. Tech Coloproctol. 2014;18:543–9.

    CAS  PubMed  Google Scholar 

  12. Sun SX, Dibonaventura M, Purayidathil FW, Wagner JS, Dabbous O, Mody R. Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey. Dig Dis Sci. 2011;56:2688–95.

    Article  PubMed  Google Scholar 

  13. Nelson AD, Camilleri M. Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities. Ther Adv Gastroenterol. 2015;8:206–20.

    Article  Google Scholar 

  14. Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014;26:1386–95. Though opioid antagonist trials often use ROME III criteria in part for responses, many will have OIC who do not fit the criteria who would benefit from PAMORAs.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Grunkemeier DM, Cassara JE, Dalton CB, Drossman DA. The narcotic bowel syndrome: clinical features, pathophysiology, and management. Clin Gastroenterol Hepatol. 2007;5:1126–39. quiz 1121–1122.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Gaertner J, Siemens W, Camilleri M, Davies A, Drossman DA, Webster LR, et al. Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J Clin Gastroenterol. 2015;49:9–16. This is an important review since many trials fail to define OIC which is a barrier to gauging responses.

    Article  CAS  PubMed  Google Scholar 

  17. Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol. 2011;106:835–42. quiz 843.

    Article  CAS  PubMed  Google Scholar 

  18. Isolauri E, Kalliomaki M, Laitinen K, Salminen S. Modulation of the maturing gut barrier and microbiota: a novel target in allergic disease. Curr Pharm Des. 2008;14:1368–75.

    Article  CAS  PubMed  Google Scholar 

  19. Bultman SJ. Emerging roles of the microbiome in cancer. Carcinogenesis. 2014;35:249–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361:512–9.

    Article  PubMed  Google Scholar 

  21. Khalif IL, Quigley EM, Konovitch EA, Maximova ID. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig Liver Dis. 2005;37:838–49.

    Article  CAS  PubMed  Google Scholar 

  22. Rousseaux C, Thuru X, Gelot A, Barnich N, Neut C, Dubuquoy L, et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med. 2007;13:35–7.

    Article  CAS  PubMed  Google Scholar 

  23. Bar F, Von Koschitzky H, Roblick U, Bruch HP, Schulze L, Sonnenborn U, et al. Cell-free supernatants of Escherichia coli Nissle 1917 modulate human colonic motility: evidence from an in vitro organ bath study. Neurogastroenterol Motil. 2009;21(559–566):e516–57.

    Google Scholar 

  24. Feng X, Su Y, Jiang J, Li N, Ding W, Wang Z, et al. Changes in fecal and colonic mucosal microbiota of patients with refractory constipation after a subtotal colectomy. Am Surg. 2015;81:198–206.

    PubMed  Google Scholar 

  25. Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. 2015;42:515–28. Many of the GI side effects from chemotherapy may be due to altered bowel flora including mucositis and weight loss as well as constipation.

    Article  CAS  PubMed  Google Scholar 

  26. Miller LE, Ouwehand AC. Probiotic supplementation decreases intestinal transit time: meta-analysis of randomized controlled trials. World J Gastroenterol. 2013;19:4718–25.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Dimidi E, Christodoulides S, Fragkos KC, Scott SM, Whelan K. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014;100:1075–84.

    Article  CAS  PubMed  Google Scholar 

  28. Touchefeu Y, Montassier E, Nieman K, Gastinne T, Potel G, Bruley des Varannes S, et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis—current evidence and potential clinical applications. Aliment Pharmacol Ther. 2014;40:409–21.

    CAS  PubMed  Google Scholar 

  29. Quigley EM. Prokinetics in the management of functional gastrointestinal disorders. J Neurogastroenterol Motil. 2015;21:330–6.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Lata PF, Pigarelli DL. Chronic metoclopramide therapy for diabetic gastroparesis. Ann Pharmacother. 2003;37:122–6.

    Article  CAS  PubMed  Google Scholar 

  31. Lyday 2nd WD, DiBaise JK. Metoclopramide-stimulated gastric emptying scintigraphy: does it predict symptom response to prokinetic therapy in chronic gastroparesis? Am J Gastroenterol. 2002;97:2474–6.

    Article  PubMed  Google Scholar 

  32. Abell TL, Camilleri M, DiMagno EP, Hench VS, Zinsmeister AR, Malagelada JR. Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility. Dig Dis Sci. 1991;36:616–20.

    Article  CAS  PubMed  Google Scholar 

  33. Busti AJ, Murillo Jr JR, Cryer B. Tegaserod-induced myocardial infarction: case report and hypothesis. Pharmacotherapy. 2004;24:526–31.

    Article  PubMed  Google Scholar 

  34. Keating GM. Prucalopride: a review of its use in the management of chronic constipation. Drugs. 2013;73:1935–50.

    Article  CAS  PubMed  Google Scholar 

  35. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358:2344–54.

    Article  CAS  PubMed  Google Scholar 

  36. Tack J. Prucalopride: a new drug for the treatment of chronic constipation. Expert Rev Gastroenterol Hepatol. 2009;3:337–43.

    Article  CAS  PubMed  Google Scholar 

  37. Tack J, Quigley E, Camilleri M, Vandeplassche L, Kerstens R. Efficacy and safety of oral prucalopride in women with chronic constipation in whom laxatives have failed: an integrated analysis. U Eur Gastroenter J. 2013;1:48–59.

    Article  CAS  Google Scholar 

  38. Cinca R, Chera D, Gruss HJ, Halphen M. Randomised clinical trial: macrogol/PEG 3350+electrolytes versus prucalopride in the treatment of chronic constipation—a comparison in a controlled environment. Aliment Pharmacol Ther. 2013;37:876–86.

    Article  CAS  PubMed  Google Scholar 

  39. Liu Z, Sakakibara R, Odaka T, Uchiyama T, Uchiyama T, Yamamoto T, et al. Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Mov Disord. 2005;20:680–6.

    Article  PubMed  Google Scholar 

  40. Mansour NM, Ghaith O, El-Halabi M, Sharara AI. A prospective randomized trial of mosapride vs. placebo in constipation-predominant irritable bowel syndrome. Am J Gastroenterol. 2012;107:792–3.

    Article  CAS  PubMed  Google Scholar 

  41. Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014;39:239–53.

    Article  CAS  PubMed  Google Scholar 

  42. Goldberg M, Li YP, Johanson JF, Mangel AW, Kitt M, Beattie DT, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation—a 4-week, randomized, double-blind, placebo-controlled, dose–response study. Aliment Pharmacol Ther. 2010;32:1102–12.

    Article  CAS  PubMed  Google Scholar 

  43. Boeckxstaens GE, Bartelsman JF, Lauwers L, Tytgat GN. Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride. Am J Gastroenterol. 2002;97:194–7.

    Article  CAS  PubMed  Google Scholar 

  44. Krogh K, Jensen MB, Gandrup P, Laurberg S, Nilsson J, Kerstens R, et al. Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury. Scand J Gastroenterol. 2002;37:431–6.

    Article  CAS  PubMed  Google Scholar 

  45. Primiano G, Plantone D, Forte F, Sauchelli D, Scaldaferri F, Gasbarrini A, et al. Acute refractory intestinal pseudo-obstruction in MELAS: efficacy of prucalopride. Neurology. 2014;82:1932–4.

    Article  PubMed  Google Scholar 

  46. Sood R, Ford AC. Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome. Ther Adv Chronic Dis. 2013;4:268–76.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, et al. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013;344:196–206.

    Article  CAS  PubMed  Google Scholar 

  48. Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107:1702–12.

    Article  CAS  PubMed  Google Scholar 

  49. Chang L, Lembo AJ, Lavins BJ, Shiff SJ, Hao X, Chickering JG, et al. The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials. Aliment Pharmacol Ther. 2014;40:1302–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Corsetti M, Tack J. Linaclotide: a new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. U Eur Gastroenter J. 2013;1:7–20.

    Article  CAS  Google Scholar 

  51. Ao M, Venkatasubramanian J, Boonkaewwan C, Ganesan N, Syed A, Benya RV, et al. Lubiprostone activates Cl- secretion via cAMP signaling and increases membrane CFTR in the human colon carcinoma cell line, T84. Dig Dis Sci. 2011;56:339–51.

    Article  CAS  PubMed  Google Scholar 

  52. Bassil AK, Borman RA, Jarvie EM, McArthur-Wilson RJ, Thangiah R, Sung EZ, et al. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br J Pharmacol. 2008;154:126–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Musch MW, Wang Y, Claud EC, Chang EB. Lubiprostone decreases mouse colonic inner mucus layer thickness and alters intestinal microbiota. Dig Dis Sci. 2013;58:668–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Whitehead WE, Palsson OS, Gangarosa L, Turner M, Tucker J. Lubiprostone does not influence visceral pain thresholds in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2011;23:944–e400.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Raschi E, De Ponti F. Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome. Expert Opin Drug Metab Toxicol. 2014;10:293–305.

    Article  CAS  PubMed  Google Scholar 

  56. Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942–7.

    Article  CAS  PubMed  Google Scholar 

  57. Schey R, Rao SS. Lubiprostone for the treatment of adults with constipation and irritable bowel syndrome. Dig Dis Sci. 2011;56:1619–25.

    Article  CAS  PubMed  Google Scholar 

  58. Chey WD, Drossman DA, Johanson JF, Scott C, Panas RM, Ueno R. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2012;35:587–99.

    Article  CAS  PubMed  Google Scholar 

  59. Spierings EL, Rauck R, Brewer R, Marcuard S, Vallejo R. (2015). Long-term safety and efficacy of lubiprostone in opioid-induced constipation in patients with chronic noncancer pain. Pain Pract.

  60. Dawson PA, Haywood J, Craddock AL, Wilson M, Tietjen M, Kluckman K, et al. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. J Biol Chem. 2003;278:33920–7.

    Article  CAS  PubMed  Google Scholar 

  61. Nagano M, Kuroki S, Mizuta A, Furukawa M, Noshiro M, Chijiiwa K, et al. Regulation of bile acid synthesis under reconstructed enterohepatic circulation in rats. Steroids. 2004;69:701–9.

    Article  CAS  PubMed  Google Scholar 

  62. Wong BS, Camilleri M, Carlson P, McKinzie S, Busciglio I, Bondar O, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2012;10(1009–1015):e1003.

    Google Scholar 

  63. Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139:1549–58. 1558 e1541.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Acosta A, Camilleri M. Elobixibat and its potential role in chronic idiopathic constipation. Ther Adv Gastroenterol. 2014;7:167–75.

    Article  CAS  Google Scholar 

  65. Wong BS, Camilleri M, McKinzie S, Burton D, Graffner H, Zinsmeister AR. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol. 2011;106:2154–64.

    Article  CAS  PubMed  Google Scholar 

  66. Simren M, Bajor A, Gillberg PG, Rudling M, Abrahamsson H. Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation—a double-blind study. Aliment Pharmacol Ther. 2011;34:41–50.

    Article  CAS  PubMed  Google Scholar 

  67. Chey WD, Camilleri M, Chang L, Rikner L, Graffner H. A randomized placebo-controlled phase IIb trial of a3309, a bile acid transporter inhibitor, for chronic idiopathic constipation. Am J Gastroenterol. 2011;106:1803–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Vahedi H, Ansari R, Mir-Nasseri M, Jafari E. Irritable bowel syndrome: a review article. Middle East J Dig Dis. 2010;2:66–77.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Vahedi H, Merat S. Is amitriptyline really effective in diarrhoea-predominant irritable bowel syndrome?: authors' reply. Aliment Pharmacol Ther. 2008;28:372–3.

    Article  PubMed  Google Scholar 

  70. Janssen P, Vos R, Tack J. The influence of citalopram on interdigestive gastrointestinal motility in man. Aliment Pharmacol Ther. 2010;32:289–95.

    Article  CAS  PubMed  Google Scholar 

  71. Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther. 2005;22:381–5.

    Article  CAS  PubMed  Google Scholar 

  72. Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55:1095–103.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Gorard DA, Libby GW, Farthing MJ. Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther. 1994;8:159–66.

    Article  CAS  PubMed  Google Scholar 

  74. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372–80.

    Article  CAS  PubMed  Google Scholar 

  75. Candy B, Jones L, Goodman ML, Drake R, Tookman A. (2011). Laxatives or methylnaltrexone for the management of constipation in palliative care patients. Cochrane Database Syst Rev. CD003448.

  76. Bharucha AE, Pemberton JH, Locke 3rd GR. American Gastroenterological Association technical review on constipation. Gastroenterology. 2013;144:218–38.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Tassinari D, Sartori S, Tamburini E, Scarpi E, Raffaeli W, Tombesi P, et al. Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. J Palliat Med. 2008;11:492–501.

    Article  PubMed  Google Scholar 

  78. Buynak R, Shapiro DY, Okamoto A, Van Hove I, Rauschkolb C, Steup 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;11:1787–804.

    Article  CAS  PubMed  Google Scholar 

  79. Lowenstein O, Leyendecker P, Hopp M, Schutter U, Rogers PD, Uhl R, et al. Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial. Expert Opin Pharmacother. 2009;10:531–43.

    Article  CAS  PubMed  Google Scholar 

  80. Cuppoletti J, Chakrabarti J, Tewari K, Malinowska DH. Methadone but not morphine inhibits lubiprostone-stimulated Cl- currents in T84 intestinal cells and recombinant human ClC-2, but not CFTR Cl- currents. Cell Biochem Biophys. 2013;66:53–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Cryer B, Katz S, Vallejo R, Popescu A, Ueno R. A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain. Pain Med. 2014;15:1825–34.

    Article  PubMed Central  PubMed  Google Scholar 

  82. Jamal MM, Adams AB, Jansen JP, Webster LR. A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain. Am J Gastroenterol. 2015;110:725–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Spierings ELH, Joswick T, Mareya S, Sun YJ, Ueno R. Lubiprostone for treatment of opioid-induced constipation does not interfere with opioid analgesic effects in patients with non-cancer pain. Pharmacotherapy. 2013;33:E223–4.

    Article  Google Scholar 

  84. Wong BS, Camilleri M. Lubiprostone for the treatment of opioid-induced bowel dysfunction. Expert Opin Pharmacother. 2011;12:983–90.

    Article  CAS  PubMed  Google Scholar 

  85. Cryer B, Lichtlen P, Wang M, Losch-Beridon T. Impact of methadone dose and baseline bowel movement frequency on efficacy of lubiprostone for opioid-induced constipation. Am J Gastroenterol. 2014;109:S532.

    Google Scholar 

  86. Sloots CEJ, Rykx A, Cools M, Kerstens R, De Pauw M. Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation. Dig Dis Sci. 2010;55:2912–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Brenner DM. Stimulant laxatives for the treatment of chronic constipation: is it time to change the paradigm? Gastroenterology. 2012;142:402–4.

    Article  PubMed  Google Scholar 

  88. Bader S, Jaroslawski K, Blum HE, Becker G. Opioid-induced constipation in advanced illness: safety and efficacy of methylnaltrexone bromide. Clin Med Insights Oncol. 2011;5:201–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Michna E, Blonsky ER, Schulman S, Tzanis E, Manley A, Zhang H, et al. Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study. J Pain. 2011;12:554–62.

    Article  CAS  PubMed  Google Scholar 

  90. Slatkin NE, Lynn R, Su C, Wang W, Israel RJ. Characterization of abdominal pain during methylnaltrexone treatment of opioid-induced constipation in advanced illness: a post hoc analysis of two clinical trials. J Pain Symptom Manag. 2011;42:754–60.

    Article  Google Scholar 

  91. Ford AC, Brenner DM, Schoenfeld PS. Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:1566–74. quiz 1575. This is an important systematic review and meta-analysis of randomized trials centered on OIC.All mu agonists have about the same effect size. Choices will come down to safety, convenience and cost.

    Article  CAS  PubMed  Google Scholar 

  92. Curran MP, Robins GW, Scott LJ, Perry CM. Alvimopan. Drugs. 2008;68:2011–9.

    Article  CAS  PubMed  Google Scholar 

  93. Paulson DM, Kennedy DT, Donovick RA, Carpenter RL, Cherubini M, Techner L, 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;6:184–92.

    Article  CAS  PubMed  Google Scholar 

  94. Webster L, Jansen JP, Peppin J, Lasko B, Irving G, Morlion B, et al. Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain. 2008;137:428–40.

    Article  CAS  PubMed  Google Scholar 

  95. Irving G, Penzes J, Ramjattan B, Cousins M, Rauck R, Spierings EL, et al. A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain. J Pain. 2011;12:175–84.

    Article  CAS  PubMed  Google Scholar 

  96. Jansen JP, Lorch D, Langan J, Lasko B, Hermanns K, Kleoudis CS, et al. A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain. J Pain. 2011;12:185–93.

    Article  CAS  PubMed  Google Scholar 

  97. Webster L, Chey W, Tack J, Lappalainen J, Barker P, Sostek M. Long-term safety and tolerability of naloxegol in patients with opioid-induced constipation. Am J Gastroenterol. 2013;108:S568–9.

    Article  Google Scholar 

  98. Webster L, Brenner D, Rolleri R, Barrett A, Bortey E, Paterson C, et al. All-cause mortality in placebo-controlled clinical trials of methylnaltrexone: a pooled analysis. Am J Gastroenterol. 2013;108:S570–1.

    Google Scholar 

  99. Corsetti M, Tack J. Naloxegol, a new drug for the treatment of opioid-induced constipation. Expert Opin Pharmacother. 2015;16:399–406.

    CAS  PubMed  Google Scholar 

  100. Bui K, She F, Hutchison M, Brunnstrom A, Sostek M. (2015). Absorption, distribution, metabolism, and excretion of [14C]-labeled naloxegol in healthy subjects. Int J Clin Pharmacol Ther.

  101. Bui K, She F, Sostek M. The effects of mild or moderate hepatic impairment on the pharmacokinetics, safety, and tolerability of naloxegol. J Clin Pharmacol. 2014;54:1368–74.

    Article  CAS  PubMed  Google Scholar 

  102. Gottfridsson C, Carlson G, Lappalainen J, Sostek M. Evaluation of the effect of naloxegol on cardiac repolarization: a randomized, placebo- and positive-controlled crossover thorough QT/QTc study in healthy volunteers. Clin Ther. 2013;35:1876–83.

    Article  CAS  PubMed  Google Scholar 

  103. Webster L, Dhar S, Eldon M, Masuoka L, Lappalainen J, Sostek M. A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation. Pain. 2013;154:1542–50.

    Article  CAS  PubMed  Google Scholar 

  104. Bruner HC, Atayee RS, Edmonds KP, Buckholz GT. Clinical utility of naloxegol in the treatment of opioid-induced constipation. J Pain Res. 2015;8:289–94.

    PubMed Central  PubMed  Google Scholar 

  105. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014;370:2387–96.

    Article  PubMed  CAS  Google Scholar 

  106. Tsuruda PR, Vickery RG, Long DD, Armstrong SR, Beattie DT. The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist. Naunyn Schmiedeberg's Arch Pharmacol. 2013;386:479–91.

    Article  CAS  Google Scholar 

  107. Sanders M, Jones S, Lowenstein O, Jansen JP, Miles H, Simpson K. New formulation of sustained release naloxone can reverse opioid induced constipation without compromising the desired opioid effects. Pain Med. 2015;16:1540–50.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cleveland Clinic Lerner School of Medicine Case, Western Reserve University, 9500 Euclid Avenue, T34, Cleveland, OH, 44195, USA

    Mellar Davis & Pamela Gamier

  2. Clinical Fellowship Program, Cleveland, OH, USA

    Mellar Davis & Pamela Gamier

  3. Palliative Medicine and Supportive Oncology Services, Taussig Cancer Institute, Cleveland, OH, USA

    Mellar Davis & Pamela Gamier

Authors
  1. Mellar Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pamela Gamier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mellar Davis.

Ethics declarations

Conflict of Interest

Mellar P. Davis and Pamela Gamier declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Palliative Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Davis, M., Gamier, P. New Options in Constipation Management. Curr Oncol Rep 17, 55 (2015). https://doi.org/10.1007/s11912-015-0481-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-015-0481-x

Keywords

Search

Navigation