Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation: a profile of its use

Katherine A Lyseng-Williamson, Katherine A Lyseng-Williamson

Abstract

Macrogol 4000, a biologically inert, non-absorbable osmotic laxative, is a highly effective and well-tolerated first-line option for the treatment of the symptoms of chronic idiopathic/functional constipation in children and adults. High-molecular-weight (HMW) macrogols ± electrolytes have generally similar efficacy profiles; however, the taste of macrogol 4000 is generally preferred over that of macrogol 3350 + electrolytes. Macrogol 4000 is more effective than lactulose in improving stool frequency and consistency, and is associated with less vomiting and flatulence. Comparisons with other osmotic and bulk-forming laxatives are limited, with macrogol 4000 being at least as, or more effective than, psyllium hydrocolloid and magnesium hydroxide in treating chronic constipation. Current clinical treatment guidelines recommend the use of HMW macrogols over the use of lactulose and bulk-forming laxative in the symptomatic treatment of constipation in children and adults.

Conflict of interest statement

K. A. Lyseng-Williamson is an employee of Adis/Springer, is responsible for the article content and declares no conflicts of interest.

References

    1. Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(9):1582–1591. doi: 10.1038/ajg.2011.164.
    1. Tamura A, Tomita T, Oshima T, et al. Prevalence and self-recognition of chronic constipation: results of an internet survey. J Neurogastroenterol Motil. 2016;22(4):677–685. doi: 10.5056/jnm15187.
    1. Shafe Anna C. E., Lee Sally, Dalrymple Jamie S. O., Whorwell Peter J. The LUCK study: Laxative Usage in patients with GP-diagnosed Constipation in the UK, within the general population and in pregnancy. An epidemiological study using the General Practice Research Database (GPRD) Therapeutic Advances in Gastroenterology. 2011;4(6):343–363. doi: 10.1177/1756283X11417483.
    1. Lindberg G, Hamid S, Malfertheiner P, et al. Constipation: a global perspective. Milwaukee: World Gastroenterology Organisation; 2010.
    1. Koppen Ilan J.N., Vriesman Mana H., Saps Miguel, Rajindrajith Shaman, Shi Xiaoxia, van Etten-Jamaludin Faridi S., Di Lorenzo Carlo, Benninga Marc A., Tabbers Merit M. Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis. The Journal of Pediatrics. 2018;198:121-130.e6. doi: 10.1016/j.jpeds.2018.02.029.
    1. Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007;25(5):599–608. doi: 10.1111/j.1365-2036.2006.03238.x.
    1. Wald A, Sigurdsson L. Quality of life in children and adults with constipation. Best Pract Res Clin Gastroenterol. 2011;25(1):19–27. doi: 10.1016/j.bpg.2010.12.004.
    1. National Institute for Health and Care Excellence (NICE). Clinical management of idiopathic constipation in children and young people. Manchester: NICE; 2015.
    1. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58(2):258–274. doi: 10.1097/MPG.0000000000000266.
    1. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2–S26. doi: 10.1038/ajg.2014.187.
    1. Vitton V, Damon H, Siproudhis L. Societe Nationale Francaise de Colo-Proctologie (SNFCP). Recommendations for the management of constipation in clinical practice: 2016 [in French] Paris: SNFCP; 2016. p. 2016.
    1. Paquette IM, Varma M, Ternent C, et al. The American Society of Colon and Rectal Surgeons’ clinical practice guideline for the evaluation and management of constipation. Dis Colon Rectum. 2016;59(6):479–492. doi: 10.1097/DCR.0000000000000599.
    1. Koppen IJN, Broekaert IJ, Wilschanski M, et al. Role of polyethylene glycol in the treatment of functional constipation in children. J Pediatr Gastroenterol Nutr. 2017;65(4):361–363. doi: 10.1097/MPG.0000000000001704.
    1. Fordtran JS, Hofmann AF. Seventy years of polyethylene glycols in gastroenterology: the journey of PEG 4000 and 3350 from nonabsorbable marker to colonoscopy preparation to osmotic laxative. Gastroenterology. 2017;152(4):675–680. doi: 10.1053/j.gastro.2017.01.027.
    1. Forlax® 4 g, powder for oral solution in sachet: summary of product characteristics. Boulogne-Billancourt: Ipsen Pharma; 2015.
    1. Forlax® 10 mg (macrogol 4000), powder for oral solution in sachet: patient information leaflet. Slough: Ipsen Ltd; 2016.
    1. Schiller LR, Emmett M, Santa Ana CA, et al. Osmotic effects of polyethylene glycol. Gastroenterology. 1988;94(4):933–941. doi: 10.1016/0016-5085(88)90550-1.
    1. Winne D, Gorig H. Appearance of 14C-polyethylene glycol 4000 in intestinal venous blood: influence of osmolarity and laxatives, effect on net water flux determination. Naunyn Schmiedebergs Arch Pharmacol. 1982;321(2):149–156. doi: 10.1007/BF00518484.
    1. Seidman EG, Hanson DG, Walker WA. Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis. Gastroenterology. 1986;90(1):120–126. doi: 10.1016/0016-5085(86)90083-1.
    1. Hammer HF, Santa Ana CA, Schiller LR, et al. Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. J Clin Invest. 1989;84(4):1056–1062. doi: 10.1172/JCI114267.
    1. Fritz E, Hammer HF, Lipp RW, et al. Effects of lactulose and polyethylene glycol on colonic transit. Aliment Pharmacol Ther. 2005;21(3):259–268. doi: 10.1111/j.1365-2036.2005.02244.x.
    1. Herve S, Leroi AM, Mathiex-Fortunet H, et al. Effects of polyethylene glycol 4000 on 24-h manometric recordings of left colonic motor activity. Eur J Gastroenterol Hepatol. 2001;13(6):647–654. doi: 10.1097/00042737-200106000-00006.
    1. Hudziak H, Bronowicki JP, Franck P, et al. Low-dose polyethylene glycol 4000: digestive effects. Randomized double-blind study in healthy subjects. Gastroenterol Clin Biol. 1996;20(5):418–423.
    1. Bernier JJ, Donazzolo Y. Effect of low-dose polyethylene glycol 4000 on fecal consistency and dilution water in healthy subjects [in French] Gastroenterol Clin Biol. 1997;21(1):7–11.
    1. Klauser AG, Muhldorfer BE, Voderholzer WA, et al. Polyethylene glycol 4000 for slow transit constipation. Z Gastroenterol. 1995;33(1):5–8.
    1. Mangin I, Bouhnik Y, Suau A, et al. Molecular analysis of intestinal microbiota composition to evaluate the effect of PEG and lactulose laxatives in humans. Microb Ecol Health Dis. 2002;14(1):54–62. doi: 10.1080/089106002760002775.
    1. Bae SH. Long-term safety of PEG 4000 in children with chronic functional constipation: a biochemical perspective. Korean J Pediatr. 2010;53(7):741–744. doi: 10.3345/kjp.2010.53.7.741.
    1. Bouhnik Y, Neut C, Raskine L, et al. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Aliment Pharmacol Ther. 2004;19(8):889–899. doi: 10.1111/j.1365-2036.2004.01918.x.
    1. Williams KC, Rogers LK, Hill I, et al. PEG 3350 administration is not associated with sustained elevation of glycol levels. J Pediatr. 2018;195:148–153. doi: 10.1016/j.jpeds.2017.11.028.
    1. Pelham RW, Nix LC, Chavira RE, et al. Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects. Aliment Pharmacol Ther. 2008;28(2):256–265. doi: 10.1111/j.1365-2036.2008.03727.x.
    1. Ragueneau I, Poirier JM, Radembino N, et al. Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers. Br J Clin Pharmacol. 1999;48(3):453–456. doi: 10.1046/j.1365-2125.1999.00025.x.
    1. Szojda MM, Mulder CJ, Felt-Bersma RJ. Differences in taste between two polyethylene glycol preparations. J Gastrointest Liver Dis. 2007;16(4):379–381.
    1. Savino F, Viola S, Erasmo M, et al. Efficacy and tolerability of PEG-only laxative on faecal impaction and chronic constipation in children: a controlled double blind randomized study vs a standard PEG-electrolyte laxative. BMC Pediatr. 2012;12:178. doi: 10.1186/1471-2431-12-178.
    1. Couturier D. Comparative study of Forlax and Transipeg in the treatment of functional constipation in the adult [in French] Ann Gastroenterol Hepatol (Paris). 1996;32(3):135–140.
    1. Ratananomgkol R, Lertmaharit S, Jongpiputvanich S. Polyethylene glycol 4000 without electrolytes versus milk of magnesia for the treatment of functional constipation in infants and young children: a randomized controlled trial. Asian Biomed. 2009;3(4):391–399.
    1. Gomes PB, Duarte MA, Melo Mdo C. Comparison of the effectiveness of polyethylene glycol 4000 without electrolytes and magnesium hydroxide in the treatment of chronic functional constipation in children [in Portuguese] J Pediatr (Rio J). 2011;87(1):24–28.
    1. DiPalma JA, DeRidder PH, Orlando RC, et al. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol. 2000;95(2):446–450. doi: 10.1111/j.1572-0241.2000.01765.x.
    1. McGraw T. Polyethylene glycol 3350 in occasional constipation: a one-week, randomized, placebo-controlled, double-blind trial. World J Gastrointest Pharmacol Ther. 2016;7(2):274–282. doi: 10.4292/wjgpt.v7.i2.274.
    1. Dipalma JA, Cleveland MV, McGowan J, et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007;102(7):1436–1441. doi: 10.1111/j.1572-0241.2007.01199.x.
    1. DiPalma JA, Cleveland MB, McGowan J, et al. A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications. South Med J. 2007;100(11):1085–1090. doi: 10.1097/SMJ.0b013e318157ec8f.
    1. Nurko S, Youssef NN, Sabri M, et al. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. J Pediatr. 2008;153(2):254–261. doi: 10.1016/j.jpeds.2008.01.039.
    1. Di Palma JA, Cleveland MV, McGowan J, et al. An open-label study of chronic polyethylene glycol laxative use in chronic constipation. Aliment Pharmacol Ther. 2007;25(6):703–708. doi: 10.1111/j.1365-2036.2006.03228.x.
    1. Dupont C, Leluyer B, Amar F, et al. A dose determination study of polyethylene glycol 4000 in constipated children: factors influencing the maintenance dose. J Pediatr Gastroenterol Nutr. 2006;42(2):178–185. doi: 10.1097/01.mpg.0000189349.17549.a9.
    1. Dziechciarz P, Horvath A, Szajewska H. Polyethylene glycol 4000 for treatment of functional constipation in children. J Pediatr Gastroenterol Nutr. 2015;60(1):65–68. doi: 10.1097/MPG.0000000000000543.
    1. Qizilbash N, Mendez I. Trends in utilization and off-label use of polyethylene glycol 4000 laxatives and the prevalence of constipation in children in France. Clin Exp Gastroenterol. 2011;4:181–188. doi: 10.2147/CEG.S23055.
    1. Bekkali NLJ, Hoekman DR, Leim O, et al. Polyethylene glycol 3350 with electrolytes versus polyethylene glycol 4000 for constipation: a randomized, controlled trial. J Pediatr Gastroenterol Nutr. 2018;66(1):10–15. doi: 10.1097/MPG.0000000000001726.
    1. Wang Y, Wang B, Jiang X, et al. Polyethylene glycol 4000 treatment for children with constipation: a randomized comparative multicenter study. Exp Ther Med. 2012;3(5):853–856. doi: 10.3892/etm.2012.491.
    1. Treepongkaruna S, Simakachorn N, Pienvichit P, et al. A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the treatment of constipation in children. BMC Pediatr. 2014;14:153. doi: 10.1186/471-2431-14-153.
    1. Dupont C, Leluyer B, Maamri N, et al. Double-blind randomized evaluation of clinical and biological tolerance of polyethylene glycol 4000 versus lactulose in constipated children. J Pediatr Gastroenterol Nutr. 2005;41(5):625–633. doi: 10.1097/01.mpg.0000181188.01887.78.
    1. Rendeli C, Ausili E, Tabacco F, et al. Polyethylene glycol 4000 vs. lactulose for the treatment of neurogenic constipation in myelomeningocele children: a randomized-controlled clinical trial. Aliment Pharmacol Ther. 2006;23(8):1259–1265. doi: 10.1111/j.1365-2036.2006.02872.x.
    1. Gordon M, MacDonald JK, Parker CE, et al. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst Rev. 2016;(8):Cd009118.
    1. Chen SL, Cai SR, Deng L, et al. Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis. Medicine (Baltimore). 2014;93(16):e65. doi: 10.1097/MD.0000000000000065.
    1. Lee-Robichaud H, Thomas K, Morgan J, et al. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010;(7):Cd007570.
    1. Chaussade S, Minic M. Comparison of efficacy and safety of two doses of two different polyethylene glycol-based laxatives in the treatment of constipation. Aliment Pharmacol Ther. 2003;17(1):165–172. doi: 10.1046/j.1365-2036.2003.01390.x.
    1. Seinela L, Sairanen U, Laine T, et al. Comparison of polyethylene glycol with and without electrolytes in the treatment of constipation in elderly institutionalized patients: a randomized, double-blind, parallel-group study. Drugs Aging. 2009;26(8):703–713. doi: 10.2165/11316470-000000000-00000.
    1. Katelaris P, Naganathan V, Liu K, et al. Comparison of the effectiveness of polyethylene glycol with and without electrolytes in constipation: a systematic review and network meta-analysis. BMC Gastroenterol. 2016;16:42. doi: 10.1186/s12876-016-0457-9.
    1. Denis P, Teillet L, Moulias R. Long-term tolerance of Forlax®: a comparative study versus lactulose in patients with functional constipation [in French]. Gastroenterologie. 1997.
    1. Chassagne P, Ducrotte P, Garnier P, et al. Tolerance and and long-term efficacy of polyethylene glycol 4000 Forlax compared to lactulose in elderly patients with chronic constipation. J Nutr Health Aging. 2017;21(4):429–439. doi: 10.1007/s12603-016-0762-6.
    1. Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. Int J Clin Pract. 2010;64(7):944–955. doi: 10.1111/j.1742-1241.2010.02397.x.
    1. Guest JF, Clegg JP, Helter MT. Cost-effectiveness of macrogol 4000 compared to lactulose in the treatment of chronic functional constipation in the UK. Curr Med Res Opin. 2008;24(7):1841–1852. doi: 10.1185/03007990802102349.
    1. Zhou L, Xia Z, Lin S, et al. A randomized controlled multicenter clinical trial on the treatment of chronic functional constipation with PEG4000. Chin J Clin Pharmacol. 2001;1:7–10.
    1. Denis P, Lerebours E. Study of the long-term tolerance of Forlax® in 16 patients treated for an average of 17 months for chronic constipation [in French] Med Chir Digest. 1996;25(5):1–4.
    1. Anton Girones M, Roan Roan J, de la Hoz B, et al. Immediate allergic reactions by polyethylene glycol 4000: two cases. Allergol Immunopathol (Madr). 2008;36(2):110–112. doi: 10.1157/13120396.
    1. Nguyen VM, Petitpain N, Lovato B, et al. Anaphylaxis to macrogol: five cases reported to the Allergy Vigilance Network [in French] Rev Fr Allergol. 2014;54(4):307–310. doi: 10.1016/j.reval.2013.10.004.
    1. Pizzimenti S, Heffler E, Gentilcore E, et al. Macrogol hypersensitivity reactions during cleansing preparation for colon endoscopy. J Allergy Clin Immunol Pract. 2014;2(3):353–354. doi: 10.1016/j.jaip.2014.01.017.
    1. Savitz JA, Durning SJ. A rare case of anaphylaxis to bowel prep: a case report and review of the literature. Mil Med. 2011;176(8):944–945. doi: 10.7205/MILMED-D-09-00176.
    1. Resolor (prucalopride) tablets: summary of product characteristics. London: European Medicines Agency; 2018.
    1. Bellini M, Usai-Satta P, Bove A, et al. Chronic constipation diagnosis and treatment evaluation: the “CHRO.CO.DI.T.E.” study. BMC Gastroenterol. 2017;17(1):11. doi: 10.1186/s12876-016-0556-7.

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