Functional constipation in childhood: Current pharmacotherapy and future perspectives

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 1, 2013, Pages 41-51

  Hoekman, Daniël Robin ^a   Benninga, Marc Alexander ^a  

^a EMMA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

Child; Functional constipation; Laxatives; Pharmacotherapy

Indexed keywords

ALVIMOPAN; BISACODYL; CISAPRIDE; CITRATE SODIUM; DISODIUM HYDROGEN PHOSPHATE; DOCUSATE SODIUM; ENEMA; LACTITOL; LACTULOSE; LINACLOTIDE; LUBIPROSTONE; MACROGOL; MACROGOL 3350; MACROGOL 4000; MAGNESIUM CITRATE; MAGNESIUM HYDROXIDE; MAGNESIUM OXIDE; MAGNESIUM SULFATE; MINERAL OIL; MOSAPRIDE; NEUROTROPHIN 3; PICOSULFATE SODIUM; PLACEBO; PRUCALOPRIDE; SENNA EXTRACT; SENNOSIDE A; SENNOSIDE B; TEGASEROD; UNINDEXED DRUG; VELUSETRAG;

ABDOMINAL PAIN; BLOATING; CARDIOVASCULAR DISEASE; CHILDHOOD DISEASE; CONSTIPATION; DIARRHEA; DRUG EFFECT; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG SAFETY; FECES IMPACTION; FLATULENCE; HUMAN; HYPERMAGNESEMIA; MAINTENANCE THERAPY; NAUSEA; RESPIRATORY TRACT INFECTION; REVIEW;

ADOLESCENT; CHILD; CHILD, PRESCHOOL; CONSTIPATION; DEFECATION; HUMANS; INFANT; LAXATIVES; POLYETHYLENE GLYCOLS; QUALITY OF LIFE; SURFACE-ACTIVE AGENTS;

EID: 84871567532     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.752816     Document Type: Review

References (114)

1. Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol 2011;25:3-18
2. Loening-Baucke V. Chronic constipation in children. Gastroenterology 1993;105:1557-64 (Pubitemid 23315336)
3. Molnar D, Taitz LS, Urwin OM, Wales JK. Anorectal manometry results in defecation disorders. Arch Dis Child 1983;58:257-61 (Pubitemid 13089460)
4. Taitz LS, Wales JK, Urwin OM, Molnar D. Factors associated with outcome in management of defecation disorders. Arch Dis Child 1986;61:472-7 (Pubitemid 16101490)
5. Di Lorenzo C. Childhood constipation: finally some hard data about hard stools! J Pediatr. 2000;136:4-7 (Pubitemid 30468547)
6. Benninga MA, Voskuijl WP, Taminiau JAJM. Childhood constipation: is there new light in the tunnel? J Pediatr Gastroenterol Nutr 2004;39:448-64
7. Bardisa-Ezcurra L, Ullman R, Gordon J. Diagnosis and management of idiopathic childhood constipation: summary of NICE guidance. BMJ 2010;340:c2585
8. Youssef NN, Langseder AL, Verga BJ, et al. Chronic childhood constipation is associated with impaired quality of life: a case-controlled study. J Pediatr Gastroenterol Nutr 2005;41:56-60 (Pubitemid 40967356)
9. Clarke MCC, Chow CS, Chase JW, et al. Quality of life in children with slow transit constipation. J Pediatr Surg 2008;43:320-4 (Pubitemid 351226217)
10. Bongers MEJ, Benninga MA, Maurice-Stam H, Grootenhuis MA. Health-related quality of life in young adults with symptoms of constipation continuing from childhood into adulthood. Health Qual Life Outcomes 2009;7:20
11. Pijpers MAM, Bongers MEJ, Benninga MA, Berger MY. Functional constipation in children: a systematic review on prognosis and predictive factors. J Pediatr Gastroenterol Nutr 2010;50:256-68
12. Bongers MEJ, van Wijk MP, Reitsma JB, Benninga MA. Long-term prognosis for childhood constipation: clinical outcomes in adulthood. Pediatrics 2010;126:e156-62
13. Mugie SM, Di Lorenzo C, Benninga MA. Constipation in childhood. Nat Rev Gastroenterol Hepatol 2011;8:502-11
14. Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527-37
15. van Wering HM, Tabbers MM, Benninga MA. Are constipation drugs effective and safe to be used in children? A review of the literature. Expert Opin Drug Saf 2012;11:71-82
16. Pijpers MAM, Tabbers MM, Benninga MA, Berger MY. Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures. Arch Dis Child 2009;94:117-31
17. Baker S, Liptak G, Colletti R. Clinical practice guideline. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric. J Pediatr Gastroenterol Nutr 2006;43:1-13
18. Tabbers MM, Boluyt N, Berger MY, Benninga MA. Clinical practice: diagnosis and treatment of functional constipation. Eur J Pediatr 2011;170:955-63
19. Benninga MA, Candy DCA, Catto-Smith AG, et al. The Paris Consensus on Childhood Constipation Terminology (PACCT) Group. J Pediatr Gastroenterol Nutr 2005;40:273-5
20. Borowitz SM, Cox DJ, Kovatchev B, et al. Treatment of childhood constipation by primary care physicians: efficacy and predictors of outcome. Pediatrics 2005;115:873-7
21. Youssef NN, Peters JM, Henderson W, et al. Dose response of PEG 3350 for the treatment of childhood fecal impaction. J Pediatr 2002;141:410-14
22. Tolia V, Lin C, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. Aliment Pharmacol Ther 1993;7:523-9 (Pubitemid 23317884)
23. Candy DCA, Edwards D, Geraint M. Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy. J Pediatr Gastroenterol Nutr 2006;43:65-70 (Pubitemid 44022388)
24. Gleghorn EE, Heyman MB, Rudolph CD. No-Enema Therapy for Idiopathic Constipation and Encopresis. Clin Pediatr (Phila) 1991;30:669-72
25. Ingebo KB. Polyethylene glycol-electrolyte solution for intestinal clearance in children with refractory encopresis. a safe and effective therapeutic program. Arch Pediatr Adolesc Med 1988;142:340-2 (Pubitemid 18087729)
26. Halabi IM. Cisapride in management of chronic pediatric constipation. J Pediatr Gastroenterol Nutr 1999;28:199-202 (Pubitemid 29293687)
27. Guest JF, Candy DC, Clegg JP, et al. Clinical and economic impact of using macrogol 3350 plus electrolytes in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction based on actual clinical practice in England and Wales. Curr Med Res Opin 2007;23:2213-25 (Pubitemid 350246607)
28. Bekkali NL, van den Berg MM, Dijkgraaf MGW, et al. Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG. Pediatrics 2009;124:e1108-15
29. Miller MK, Dowd MD, Friesen CA, Walsh-Kelly CM. A randomized trial of enema versus polyethylene glycol 3350 for fecal disimpaction in children presenting to an emergency department. Pediatr Emerg Care 2012;28:115-19
30. Farahmand F, Eftekhari K, Modarresi V, et al. Comparing oral route paraffin oil versus rectal route for disimpaction in children with chronic constipa. Iran J Pediatr 2010;20:291-6
31. Benninga MA, Berger MY, Boluyt N, Tabbers MM. Richtlijn obstipatie bij kinderen van 0 tot 18 jaar 2009. NVK; Utrecht: 2009
32. Hansen SE, Whitehill JL, Goto CS, et al. Safety and efficacy of milk and molasses enemas compared with sodium phosphate enemas for the treatment of constipation in a pediatric emergency department. Pediatr Emerg Care 2011;27:1118-20
33. Walker M, Warner BW, Brilli RJ, Jacobs BR. Cardiopulmonary compromise associated with milk and molasses enema use in children. J Pediatr Gastroenterol Nutr 2003;36:144-8 (Pubitemid 41672636)
34. Sheibani S, Gerson LB. Chemical colitis. J Clin Gastroenterol 2008;42:115-21
35. Burgers R, Bonanno E, Madarena E, et al. The care of constipated children in primary care in different countries. Acta Paediatr 2012;101:677-80
36. Schiller LR. Review article: the therapy of constipation. Aliment Pharmacol Ther 2001;15:749-63 (Pubitemid 32500421)
37. Perkin JM. Constipation in childhood: a controlled comparison between lactulose and standardized senna. Curr Med Res Opin 1977;4:540-3 (Pubitemid 8093779)
38. Martino AM, Pesce F, Rosati U. The effects of lactitol in the treatment of intestinal stasis in childhood. Minerva Pediatr 1992;44:319-23
39. Pitzalis G, Deganello F, Mariani P, et al. Lactitol in chronic idiopathic constipation in children. Pediatr Med Chir 1995;17:223-6
40. Kokke FTM, Scholtens PAMJ, Alles MS, et al. A dietary fiber mixture versus lactulose in the treatment of childhood constipation: a double-blind randomized controlled trial. J Pediatr Gastroenterol Nutr 2008;47:592-7
41. Brady CE, DiPalma JA, Morawski SG, et al. Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution. Gastroenterology 1986;90:1914-18 (Pubitemid 16085598)
42. 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;17:165-72 (Pubitemid 36140447)
43. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study. Arch Dis Child 2007;92:996-1000 (Pubitemid 350043974)
44. Nurko S, Youssef N, Sabri M. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. J Pediatr 2008;153:254-61
45. Plunkett A, Phillips CP, Beattie RM. Management of chronic functional constipation in childhood. Paediatr Drugs 2007;9:33-46
46. 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;41:625-33 (Pubitemid 41579674)
47. Gremse DA, Hixon J, Crutchfield A. Comparison of Polyethylene Glycol 3350 and Lactulose for Treatment of Chronic Constipation in Children. Clin Pediatr (Phila) 2002;41:225-9 (Pubitemid 34522477)
48. Voskuijl W, de Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial. Gut 2004;53:1590-4 (Pubitemid 39434101)
49. Wang BX, Wang MG, Jiang MZ, et al. Forlax in the treatment of childhood constipation: a randomized, controlled, multicenter clinical study. Zhongguo Dang Dai Er Ke Za Zhi 2007;9:429-32
50. 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;3:853-6
51. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev 2010;7:CD007570
52. Gordon M, Naidoo K, Akobeng AK, Thomas AG. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst Rev 2012;7:CD009118
53. Quitadamo P, Coccorullo P, Giannetti E, et al. A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood. J Pediatr 2012;161(4):710-15
54. Bae SH. Long-term safety of PEG 4000 in children with chronic functional constipation: a biochemical perspective. Korean J Pediatr 2010;53:741-4
55. Pashankar DS, Loening-Baucke V, Bishop WP. Safety of polyethylene glycol 3350 for the treatment of chronic constipation in children. Arch Pediatr Adolesc Med 2003;157:661-4 (Pubitemid 36818646)
56. Donowitz M. Current concepts of laxative action: mechanisms by which laxatives increase stool water. J Clin Gastroenterol 1979;1:77-84 (Pubitemid 11162261)
57. Donowitz M, Rood R. Magnesium hydroxide: new insights into the mechanism of its laxative effect and the potential involvement of prostaglandin E2. J Clin Gastroenterol 1992;14:20-6
58. Ikarashi N, Ushiki T, Mochizuki T, et al. Effects of magnesium sulphate administration on aquaporin 3 in rat gastrointestinal tract. Biol Pharm Bull 2011;34:238-42
59. Gomes PB, Duarte MA, de Melo MCB. Comparison of the effectiveness of polyethylene glycol 4000 without electrolytes and magnesium hydroxide in the treatment of chronic functional constipation in children. J Pediatr (Rio J) 2011;87:24-8
60. Loening-Baucke V, Pashankar DS. A randomized, prospective, comparison study of polyethylene glycol 3350 without electrolytes and milk of magnesia for children with constipation and fecal incontinence. Pediatrics 2006;118:528-35 (Pubitemid 46085407)
61. Ratanamongkol P. 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 (Res Rev News) 2009;3:391-9
62. Alison LH, Bulugahapitiya D. Laxative induced magnesium poisoning in a 6 week old infant. BMJ 1990;300:125 (Pubitemid 20031593)
63. Mofenson HC, Caraccio TR. Magnesium intoxication in a neonate from oral magnesium hydroxide laxative. J Toxicol Clin Toxicol 1991;29:215-22
64. Sullivan JE, Berman BW. The pediatric forum: hypermagnesemia with lethargy and hypotonia due to administration of magnesium hydroxide to a 4-week-old infant. Arch Pediatr Adolesc Med 2000;154:1272-4
65. Kutsal E, Aydemir C, Eldes N, et al. Severe hypermagnesemia as a result of excessive cathartic ingestion in a child without renal failure. Pediatr Emerg Care 2007;23:570-2 (Pubitemid 47339801)
66. Emmanuel AV, Tack J, Quigley EM, Talley NJ. Pharmacological management of constipation. Neurogastroenterol Motil 2009;21(Suppl 2):41-54
67. Sharif F, Crushell E, O'Driscoll K, Bourke B. Liquid paraffin: a reappraisal of its role in the treatment of constipation. Arch Dis Child 2001;85:121-4 (Pubitemid 32701678)
68. Urganci N, Akyildiz B, Polat T. A comparative study: the efficacy of liquid paraffin and lactulose in management of chronic functional constipation. Pediatr Int 2005;47:15-19 (Pubitemid 40314604)
69. Farahmand F. A randomised trial of liquid paraffin versus lactulose in the treatment of chronic functional constipation in children. Acta Med Iran 2007;45:183-8 (Pubitemid 350133485)
70. Rafati M, Karami H, Salehifar E, Karimzadeh A. Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation. Daru 2011;19:154-8
71. Sondheimer J, Gervaise E. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr 1982;1:223-6 (Pubitemid 12013438)
72. Bandla HP, Davis SH, Hopkins NE. Lipoid pneumonia: a silent complication of mineral oil aspiration. Pediatrics 1999;103:E19
73. Zanetti G, Marchiori E, Gasparetto TD, et al. Lipoid pneumonia in children following aspiration of mineral oil used in the treatment of constipation: high-resolution CT findings in 17 patients. Pediatr Radiol 2007;37:1135-9 (Pubitemid 47561852)
74. Tabbers MM, Boluyt N, Berger MY, Benninga MA. Constipation in children. Clin Evid 2010;04:303
75. Tack J. Current and future therapies for chronic constipation. Best Pract Res Clin Gastroenterol 2011;25:151-8
76. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol 2003;36:386-9
77. Muller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100:232-42 (Pubitemid 41623292)
78. Kamm MA, Muller-Lissner S, Wald A, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol 2011;9:577-83
79. Muller-Lissner SA, Kamm MA, Wald A, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol 2010;105:897-903
80. Manabe N, Cremonini F, Camilleri M, et al. Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers. Aliment Pharmacol Ther 2009;30:930-6
81. Ewe K. Einfluss eines diphenolischen Laxans (Bisacodyl) auf den Wasser-und Elektrolyttransport im menschlichen Colon. Klin Wochenschr 1974;52:827-33
82. Price KJ, Elliot TM. What is the role of stimulant laxatives in the management of childhood constipation and soiling? Cochrane Database Syst Rev 2001;3:CD002040
83. Wald A. Chronic constipation: advances in management. Neurogastroenterol Motil 2007;19:4-10 (Pubitemid 44952773)
84. Leng-Peschlow E. Sennoside-induced secretion and its relevance for the laxative effect. Pharmacology 1993;47(Suppl 1):14-21 (Pubitemid 23291010)
85. Tack J, Muller-Lissner S, Stanghellini V, et al. Diagnosis and treatment of chronic constipation-a European perspective. Neurogastroenterol Motil 2011;23:697-710
86. Berg I, Forsythe I, Holt P, Watts J. A controlled trial of "Senokot" in faecal soiling treated by behavioural methods. J Child Psychol Psychiatry 1983;24:543-9
87. Bongers MEJ, van den Berg MM, Reitsma JB, et al. A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation. Clin Gastroenterol Hepatol 2009;7:1069-74
88. Liem O, Benninga MA, Mousa HM, Di Lorenzo C. Novel and alternative therapies for childhood constipation. Curr Gastroenterol Rep 2007;9:214-18 (Pubitemid 46864639)
89. Emmanuel A. Current management strategies and therapeutic targets in chronic constipation. Therap Adv Gastroenterol 2011;4:37-48
90. Benninga MA, Candy DCA, Taminiau JA. New treatment options in childhood constipation? J Pediatr Gastroenterol Nutr 2005;41(Suppl 1):S56-7 (Pubitemid 41291450)
91. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007;132:397-414 (Pubitemid 46127672)
92. De Maeyer JH, Lefebvre RA, Schuurkes JAJ. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil 2008;20:99-112
93. Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther 2012;35:745-67
94. Aboumarzouk O, Agarwal T. Cisapride for intestinal constipation. Cochrane Database Syst Rev 2011;1:CD007780
95. Liem O, Mousa HM, Benninga MA, Di Lorenzo C. Tegaserod use in children: a single-center experience. J Pediatr Gastroenterol Nutr 2008;46:54-8
96. Furlano RI, Sidler MA, Beglinger C. P0465 Tegaserod: a pro-kinetic agent for the treatment of chronic functional constipation in children? J Pediatr Gastroenterol Nutr 2004;39:S233
97. Tack J, Corsetti M. Prucalopride: evaluation of the pharmacokinetics, pharmacodynamics, efficacy and safety in the treatment of chronic constipation. Expert Opin Drug Metab Toxicol 2012;8:1327-35
98. Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut 2011;60:209-18
99. Winter HS, Ausma J, Vandeplassche L. An open label follow-up study of prucalopride solution in pediatric subjects with functional fecal retention. Gastroenterology 2009;136:129
100. Goldberg M, Li Y-P, Johanson JF, 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
101. Kim HS, Choi EJ, Park H. The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro. Neurogastroenterol Motil 2008;20:169-76
102. Camilleri M. Alvimopan, a selective peripherally acting mu-opioid antagonist. Neurogastroenterol Motil 2005;17:157-65 (Pubitemid 40476675)
103. Camilleri M, Bharucha AE, Ueno R, 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
104. Lacy BE, Levy LC. Lubiprostone: a chloride channel activator. J Clin Gastroenterol 2007;41:345-51 (Pubitemid 46573059)
105. Chiou E, Nurko S. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents. Expert Rev Gastroenterol Hepatol 2010;4:293-304
106. Parkman H. Neurotrophin-3 improves functional constipation. Am J Gastroenterol 2003;98:1338-47 (Pubitemid 36741532)
107. Spriggs M, Caldwell PHY. The ethics of paediatric research. J Paediatr Child Health 2011;47:664-7
108. Caldwell PHY, Butow PN, Craig JC. Pediatricians' attitudes toward randomized controlled trials involving children. J Pediatr 2002;141:798-803 (Pubitemid 35471641)
109. Caldwell PHY, Butow PN, Craig JC. Parents' attitudes to children's participation in randomized controlled trials. J Pediatr 2003;142:554-9 (Pubitemid 36623567)
110. Caldwell PHY, Murphy SB, Butow PN, Craig JC. Clinical trials in children. Lancet 2004;364:803-11 (Pubitemid 39165102)
111. Hoppu K, Anabwani G, Garcia-Bournissen F, et al. The status of paediatric medicines initiatives around the world-What has happened and what has not? Eur J Clin Pharmacol 2012;68:1-10
112. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European network for drug investigation in children. BMJ 2000;320:79-82 (Pubitemid 30173044)
113. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164:552-8 (Pubitemid 41225059)
114. Chrzan R, Klijn AJ, Vijverberg MAW, et al. Colonic washout enemas for persistent constipation in children with recurrent urinary tract infections based on dysfunctional voiding. Urology 2008;71:607-10