Are constipation drugs effective and safe to be used in children?: A review of the literature

Expert Opinion on Drug Safety

Volumn 11, Issue 1, 2012, Pages 71-82

  Van Wering, Herbert M ^a   Tabbers, Merit M ^a   Benninga, Marc A ^a  

^a EMMA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

Children; Constipation; Efficacy; Laxatives; Review; Safety

Indexed keywords

BISACODYL; DOCUSATE SODIUM; ENEMA; LACTULOSE; LAXATIVE; LIQUID PARAFFIN; LUBIPROSTONE; MACROGOL; MACROGOL 3350; MACROGOL 4000; MAGNESIUM CITRATE; MAGNESIUM HYDROXIDE; PRUCALOPRIDE; SENNA EXTRACT; SODIUM DIHYDROGEN PHOSPHATE;

ABDOMINAL CRAMP; ABDOMINAL DISCOMFORT; ABDOMINAL PAIN; ASPIRATION PNEUMONIA; BLISTER; BLOATING; BRONCHOSPASM; CHILDHOOD DISEASE; COMA; CONSTIPATION; DIARRHEA; DIETARY FIBER; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG USE; FLATULENCE; HUMAN; HYPERMAGNESEMIA; HYPERNATRAEMIA; HYPERPHOSPHATEMIA; HYPOCALCEMIA; HYPOKALEMIA; HYPOTHERMIA; LUNG EDEMA; MALLORY WEISS SYNDROME; METABOLIC ACIDOSIS; NAUSEA; NEOPLASM; PERFORATION; PNEUMATOSIS INTESTINALIS; PNEUMOPERITONEUM; PULMONARY ASPIRATION; RASH; REVIEW; SINGLE DRUG DOSE; SKIN EXFOLIATION; STOMACH MUCOSA LESION;

ADULT; AGE FACTORS; ANIMALS; CHILD; CHRONIC DISEASE; CLINICAL TRIALS AS TOPIC; CONSTIPATION; DRUG DESIGN; HUMANS; LAXATIVES; QUALITY OF LIFE;

EID: 84555217856     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2011.604631     Document Type: Review

References (117)

1. Rasquin A, DiLorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527-37
2. Peppas G, Alexiou VG, Mourtzoukou E, Falagas ME. Epidemiology of constipation in Europe and Oceania: a systematic review. BMC Gastroenterol 2008;8:5
3. van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol 2006;101:2401-9 (Pubitemid 44477568)
4. Baker SS, Liptak GS, Colletti RB, et al. Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 1999;29:612-26
5. Rasquin-Weber A, Hyman PE, Cucchiarra S, et al. Childhood functional gastrointestinal disorder. Gut 1999;45(Suppl 2):1160-8
6. Hyman PE, Milla PJ, Benninga MA, et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2006;130:1519-26
7. Voskuijl WO, Heijmans J, Heijmans HS, et al. Use of Rome II criteria in childhood defecation disorders: appilcability in clinical and research practice. J Pediatr 2004;145:213-17 (Pubitemid 38993394)
8. Benninga MA, Candy DC, Catto-Smith AG, et al. The Paris Consensus on Childhood Constipation Terminology (PACCT) group. J Pediatr Gastroenterol Nutr 2005;40:273-5
9. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006;130:1480-91
10. Benninga MA, Voskuijl WP, Taminiau JA. Childhood constipation: is there new light in the tunnel? J Pediatr Gastroenterol Nutr 2004;39:448-64
11. The North American Society for Pediatric Gastroenterology and Nutrition. Evaluation and treatment of constipation in children: summary of updated recommendations of the North American Society for Pediatric Gastroenterology and nutrition. J Pediatr Gastroenterol Nutr 2006;43:405-7
12. Ramkumar D, Rao SSC. Efficacy and Safety of traditional medical therapies for chronic constipation; systematic review. Am J Gastroenterol 2005;100:936-71 (Pubitemid 40592390)
13. Tabbers MM, Boluyt N, Berger MY, Benninga MA. Constipation in children. Clin Evid 2010;03:303
14. Bardisa-Ezcurra L, Ullman R, Gordon J; on behalf of the guideline development group. Diagnosis and management of idiopathic childhood constipation: summary of NICE guidance. BMJ 2010;340:c2585
15. Pijpers MA, Tabbers MM, Benninga MA, Berger MY. Currently recommended treatments of childhood constipation are not evidence based: a systematic review on the effect of laxative treatment and dietary measures. Arch Dis Child 2009;94:117-31
16. Pijpers MAM, Bongers MEJ, Benninga MA, Berger MY. Functional constipation in children: A systemic review on prognosis and predictive factors. J Pediatr Gastroenterol Nutr 2010;50:256-68
17. Farrell M, Holmes G, Coldicutt P, Peak M. Management of childhood constipation: parents' experiences. J Adv Nurs 2003;44:479-89 (Pubitemid 37548524)
18. Bongers MEJ, van Wijk MP, Reitsma JB, Benninga MA. Long-term prognosis for childhood constipation: clinical outcomes in adulthood. Pediatrics 2010;126:e156-62
19. van Ginkel R, Reitsma JB, Buller HA, et al. Childhood constipation: longitudinal follow-up beyond puberty. Gastroenterology 2003;125:357-63 (Pubitemid 36929415)
20. Talley NJ. Definitions, epidemiology, and impact of chronic constipation. Rev Gastroenterol Disord 2004;4:S3-10
21. Bongers MEJ, van Dijk M, Benninga MA, Grootenhuis MA. Health related quality of life in children with constipation-associated fecal incontinence. J Pediatr 2009;154:749-53
22. 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)
23. Chao HC, Chen SY, Chen CC, et al. The impact of constipation on growth in children. Pediatr Res 2008;64:308-11
24. Liem O, Harman J, Benninga M, et al. Health utilization and cost impact of childhood constipation in the United States. J Pediatr 2009;154:258-62
25. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics 2005;23:461-76 (Pubitemid 40994135)
26. Halabi IM. Cisapride in management of chronic pediatric constipation. J Pediatr Gastroenterol Nutr 1999;28:199-202 (Pubitemid 29293687)
27. 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
28. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm173074.htm
29. Available from: www.fda.gov/CDER/DRUG/advisory/tegaserod
30. Aboumarzouk OM, Agarwal T, Antakia R, et al. Cisapride for intestinal constipation. Cochrane Database Syst Rev 2011;1:CD007780
31. Barish CF, Drossman D, Johanson JF, Ueno R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci 2010;55:1090-7
32. Lembo AJ, Kurtz CB, Macdougall JE, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology 2010;138:886-95
33. Frampton JE. Prucalopride. Drugs 2009;69:2463-76
34. Goldberg M, Li YP, 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
35. Elkington SG. Lactulose. Gut 1970;11:1043-8
36. Clark JH, Russell GJ, Fitzgerald JF, et al. Serum beta-carotene, retinol, and alpha-tocopherol levels during mineral oil therapy for constipation. Am J Dis Child 1987;141:1210-12 (Pubitemid 17163484)
37. Lennard-Jones JE. Chapter 40: clinical aspects of laxatives, enemas and suppositories. In: Kamm MA, Lennard-Jones JE. editor. Constipation. Wrightson biomedical Publishing Ltd; Petersfield, UK and Bristol, PA, USA 1994
38. Leng-Peschlow E. Senna and its rational use. Pharmacology 1992;44:1-52
39. Biggs WS, Dery WH. Evaluation and treatment of constipation in infants and children. Am Fam Physician 2006;73:469-77,479-81
40. Bekkali NL, van den Berg MM, Dijkgraaf MG, et al. Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG. Pediatrics 2009;124:e1108-15
41. Youssef NN, Peters JM, Henderson W, et al. Dose response of PEG 3350 for the treatment of childhood fecal impaction. J Pediatr 2002;141(3):410-14
42. Plunkett A, Phillips CP, Beattie RM. Management of chronic functional constipation in childhood. Pediatr Drugs 2007;991:33-46
43. Candy D, Belsey J. Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: a systemic review. Arch Dis Child 2009;94:156-60
44. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double, placebo controlled crossover study. Arch Dis Child 2007;92:996-1000 (Pubitemid 350043974)
45. 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;153:254-61
46. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene Glycol for chronic constipation (review). Cochrane Database Syst Rev 2010;7:CD007570
47. Candy DCA, Edwards D, Geraint M, et al. Treatment of fecal impaction with polyethylene glycol plus electrolytes (PEG+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)
48. 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)
49. 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)
50. Voskuijl WP, 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)
51. 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
52. Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. Int J Clin Pract 2010;64:944-55
53. Loening-Baucke V, Pashankar D. 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)
54. Loening-Baucke V. Polyethylene glycol without electrolytes for children with constipation and encopresis. J Pediatr Gastroenterol Nutr 2002;34:372-7 (Pubitemid 34568539)
55. Gal-Ezer S, Shaoul R. The safety of mineral oil in the treatment of constipation-a lesson from prolonged overdose. Clin Pediatr (Phila) 2006;45:865-8
56. Urganci N, Akyildiz B, Polata TB. A comparative study: the efficacy of liquid parrafin and lactulose in management of chronic functional constipation. Pediatr Int 2005;47:15-19 (Pubitemid 40314604)
57. 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)
58. Sondheimer JM, Gervaise EP. 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)
59. Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of fecal impaction in children. Aliment Pharmacol Ther 1993;7:423-9
60. McClung HJ, Potter C. Rational use of laxatives in children. Adv Pediatr 2004;51:231-62 (Pubitemid 39303481)
61. 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
62. Nolan T, Debelle G, Oberklaid F, Coffey C. Randomized trial of laxatives in treatment of childhood encopresis. Lancet 1991;338:523-7
63. 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
64. Perkin J. Constipation in childhood: a controlled comparison between lactulose and standardized senna. Curr Med Res Opin 1977;4:540-3 (Pubitemid 8093779)
65. Kamm MA, Mueller-Lissner S, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol 2011;25,9:577-83
66. Mueller-Lissner S, 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
67. Loening-Baucke V, Krishna R, Pashankar DS. Polyethylene glycol 3350 without electrolytes for the treatment of functional constipation in infants and toddlers. J Pediatr Gastroenterol Nutr 2004;39:536-9
68. Loening-Baucke V. Prevalence, symptoms and outcome of constipation in infants and toddlers. J Pediatr 2005;146:359-63 (Pubitemid 40341746)
69. Michail S, Gendy E, Pread'Homme D, Mezoff A. Polyethylene glycol for constipation in children younger than eighteen months old. J Pediatr Gastroenterol Nutr 2004;39:197-9
70. 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)
71. McGuire JK, Kulkarni MS, Baden HP. Fatal hypermagnesemia in a child treated with megavitamin/megamineral therapy. Pediatrics 2000;1059:E18
72. Ashton MR, Sutton D, Nielsen M. Severe magnesium toxicity after magnesium sulphate enema in a chronically constipated child. BMJ 1990;24:541 (Pubitemid 20085556)
73. Alison LH, Bulugahapitiya D. Laxative induced magnesium poisoning in a 6 week old infant. BMJ 1990;300:125 (Pubitemid 20031593)
74. Goodman RA, Riley TR III. Lactulose-induced pneumatosis intestinalis and pneumoperitoneum. Dig Dis Sci 2001;46:2549-53 (Pubitemid 33042365)
75. Nelson DC, McGrew WR Jr, Hoyumpa AM Jr. Hypernatremia and lactulose therapy. JAMA 1983;249:1295-8 (Pubitemid 13147775)
76. Seki N, Hamano H, Iiyama Y, et al. Effect of lactulose on calcium and magnesium absorption; a study using stable isotopes in adult men. J Nutr Sci Vitaminol (Tokyo) 2007;53:5-12 (Pubitemid 46623911)
77. Nilsson SE, Takkinen S, Johansson B, et al. Laxative treatment elevates plasma homocysteine: a study on a population-based Swedish sample of old people. Eur J Clin Pharmacol 2004;60:45-9 (Pubitemid 38471457)
78. 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;19:889-99 (Pubitemid 38534818)
79. Riskin A, Hochwald O, Bader D, et al. The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. J Pediatr 2010;156:209-14
80. Bae SH. Long-term safety of PEG 4000 in children with chronic functional constipation: a biochemical perspective. Korean J Pediatr 2010;53:741-4
81. 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;157:660-4
82. McBride MA, Vanagunas A. Esophageal perforation associated with polyethylene glycol electrolyte lavage solution. Gastrointest Endosc 1993;39:856-7 (Pubitemid 23346579)
83. Schwartz T. Polyethylene glycol electrolyte lavage solution-induced Mallory-Weiss tear. Gastroenterol Nurs 1995;18:233-4
84. Stollman N,Manten HD. Angioedema from oral polyethylene glycol electrolyte lavage solution. Gastrointest Endosc 1996;44:209-10 (Pubitemid 26271929)
85. Schuman E, Balsam PE. Probable anaphylactic reaction to polyethylene glycol electrolyte lavage solution. Gastrointest Endosc 1991;37:411
86. Narsinghani U, Chadha M, Farrar HC, Anand KS. Lifethreatening respiratory failure following accidental infusion of polyethylene glycol electrolyte solution into the lung. J Toxicol Clin Toxicol 2001;39:105-7 (Pubitemid 32335495)
87. Argent A, Hatherill M, Reynolds L, Purves L. Fulminant pulmonary oedema after administration of a balanced electrolyte polyethylene glycol solution. Arch Dis Child 2002;86:209 (Pubitemid 34250871)
88. Sharif F, Crushell E, O'Driscoll K, et al. Liquid paraffin: a reappraisal of its role in the treatment of constipation. Arch Dis Child 2001;85:121-4 (Pubitemid 32701678)
89. Bandla HPR, Davis SH, Hopkins NE. Lipoid pneumonia: a silent complication of mineral oil aspiration. Pediatrics 1999;103:e19
90. Sharma D, Hilinski JA. Refractory pneumonia in a Mexican American infant. Clin Pediatr (Phila) 2010;49:710-12
91. Zanetti G, Marchiori E, Gasparetto TD, et al. Lipoid pneumonia in children following aspiration of mineral oil used in treatment of constipation: high-resolution CT findings in 17 patients. Pediatr Radiol 2007;37:1135-9 (Pubitemid 47561852)
92. Committee on safety of medicines. Liquid paraffin: restricted indications and availability. CSM; London; 1990. p. 28
93. Gattuso JM, Kamm MA. Adverse effects of drugs used in the management of constipation and diarrhoea. Drug Saf 1994;10(1):47-65 (Pubitemid 24032938)
94. Muller-Lissner SA, Kamm MA, Scarpignato C, et al. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100:232-42 (Pubitemid 41623292)
95. Spiller HA, Winter ML, Weber JA, et al. Skin breakdown and blisters from senna-containing laxatives in young children. Ann Pharmacother 2003;37:636-9 (Pubitemid 36523054)
96. Pockros PJ, Foroozan P. Golytely lavage versus a standard colonoscopy preparation. Effect on normal colonic mucosal histology. Gastroenterology 1985;88(2):545-8 (Pubitemid 15194722)
97. Speare GS. Melanosis coli. Experimental observations on its production and elimination in twenty-three cases. Am J Surg 1951;82:631-7
98. Willems M, van Buuren HR, de Krijger R. Anthranoid selfmedication causing rapid development of melanosis coli. Neth J Med 2003;61:22-4 (Pubitemid 39106988)
99. Fioramonti J, Bueno L. Toxicity of laxatives: How to discriminate between myth and fact? Eur J Gastroenterol Hepatol 1995;7:5-7
100. Riecken EO, Zeitz M, Emde C, et al. The effect of an anthraquinone laxative on colonic nerve tissue: a controlled trial in constipated women. Z Gastroenterol 1990;28:660-4
101. van Gorkum BA, de Vries EG, Karrenbeld A, et al. Review article: Anthranoid laxatives and their potential carcinogenic effects. Aliment Pharmacol Ther 1999;13:443-52 (Pubitemid 29176866)
102. Roberts MC, Millikan RC, Galanko JA, et al. Constipation, laxative use, and colon cancer in a North Carolina population. Am J Gastroenterol 2003;98:857-64 (Pubitemid 36576314)
103. Preston DM, Lennard-Jones JE. Severe chronic constipation of young women: idiopathic slow transit constipation. Gut 1986;27:41-8 (Pubitemid 16134474)
104. Dunnick JK, Hailey JR. Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems. Cancer Res 1996;56:4922-6 (Pubitemid 26374430)
105. Cooper GS, Longnecker MP, Peters RK. Ovarian cancer risk and use of phenolphthalein-containing laxatives. Pharmacoepidemiol Drug Saf 2004;13:35-9 (Pubitemid 38159267)
106. Bell AM. Colonic perforation with a phosphate enema. J R Soc Med 1990;83:54-5 (Pubitemid 20112195)
107. Mendoza J, Legido J, Rubio S, Gisbert JP. Systematic review: the adverse effects of sodium phosphate enema. Aliment Pharmacol Ther 2007;26:9-20 (Pubitemid 46889844)
108. Bowers B. Evaluating the evidence for administrating phosphate enemas. Br J Nurs 2006;15:378-81
109. Walton DM, Thomas DC, Aly HZ, et al. Morbid hypocalcemia associated with phosphate enema in a six-week-old infant. Pediatrics 2000;106:E37
110. Martin RR, Lisehore GR, Braxton M Jr, et al. Fatal poisoning from sodium phosphate enema. Case report and experimental study. JAMA 1987;257:2190-2 (Pubitemid 17055843)
111. Ismail EA, Al-Mutairi G, Al-Anzy H. A fatal small dose of phosphate enema in a young child with no renal or gastrointestinal abnormality. J Pediatr Gastroenterol Nutr 2000;30:220-1 (Pubitemid 30366205)
112. Rimensberger P, Schubiger G, Willi U. Connatal rickets following repeated administration of phosphate enemas in pregnancy: a case report. Eur J Pediatr 1992;151:54-6
113. Ballesteros Garcia M, Sanchez Diaz JI, Mar Molinero F. Poisoning after the use of Sodium phosphate enema. An Esp Pediatr 2001;55:92-3 (Pubitemid 34835790)
114. 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
115. Rabah R, Evans RW, Yunis EJ. Mineral oil embolization and lipid pneumonia in an infant treated for Hirschsprung's disease. Pediatr Pathol 1987;7:447-55 (Pubitemid 18042563)
116. Muller-Lissner S, Wald A. Constipation in adults. Clin Evid (Online) 2010;7:pii0413
117. Kaye JL. Review of paediatric gastrointestinal physiology data relevant to oral drug delivery. Int J Clin Pharm 2011;33:20-4