Friday, April 25, 2014

Is polyethylene glycol safe and effective for chronic constipation in children?

Chronic constipation is a frequently encountered problem in the paediatric wards and clinics. Your usual line of management has been to prescribe adequate doses of regular lactulose and use sodium picosulphate as a second line laxative or as add on treatment. Recently, you have become aware of a new drug—polyethylene glycol (PEG). As you have not prescribed this drug earlier, you want to appraise the evidence before using it in your clinical practice.

Commentary

Chronic constipation in children is a common gastrointestinal disorder encountered in general paediatric clinics and forms a substantial part of the paediatric gastroenterologist’s workload. The majority of constipated children have functional constipation and despite laxative use, success is modest. Management options include a combination of healthy eating aimed at increasing fibre and fluid intake, regular toileting, reinforcement with appropriate rewards, and laxative therapy. Combining laxative use with behavioural therapy has been shown to be better than laxative use alone.12 A high level of motivation and perseverance are necessary for these measures to be successful, and hence a continued search for a better laxative in terms of efficacy, safety, and compliance continues.
High dose PEG with electrolytes has been available for intestinal lavage preceding radiological and surgical procedures in children for some time. The electrolytes are added to prevent their loss through the faeces due to the large volume of the lavage, but this gives the lavage solution an unpleasant salty taste. A low dose version, such as PEG 3350, is available with electrolytes (in the UK and Netherlands) or without electrolytes (in the USA); it has been in commercial use only in the last few years and is used in much smaller volumes. It has been classed as an iso-osmotic laxative and acts by opposing absorption of water from faecal material in the large bowel and thus retaining water in the faeces, which is different from the laxatives such as lactulose which draw fluid from the body into the bowel lumen due to its high osmotic load.13PEG is physiologically inert and is not absorbed or metabolised in the gut, giving it an unlimited “ceiling of action”.13
From the available evidence it is clear that PEG is effective for both disimpaction and maintenance in children of all age groups with chronic constipation. The compliance with PEG treatment is high. In the controlled studies,1–4 PEG has been shown to be more effective than a placebo and lactulose, and at least as effective as milk of magnesia, with a much higher compliance than any of the others. It seems safe with or without added electrolytes. Only one of the above studies actually assessed the serum electrolyte levels post-treatment; abnormal levels were not found.10 Literature search did not reveal any case reports of adverse effects to the use of low dose PEG 3350 with or without electrolytes.
There are still some unresolved questions such as the issue of adding electrolytes, the most effective molecular weight of PEG (PEG 3350 v PEG 4000), and the safety profile of the drug in all age groups. The drug appears promising, and though its use at present is mainly in those with inadequate response to other laxatives, it is increasingly being used as first line treatment.
Comment: In India we have had Laxopeg (PEG 3350 without electrolytes) and Ezlax (Macrogol 4000) available for some time now. Since my daughter has functional constipation, I have been using these for a long time now. Now Dr Reddy's has come with a formulation (MuOUT - PEG 3350 with electrolytes), and I was trying to figure out which is the better formulation.
Here is what I feel. 
  • Ezlax is cheaper - Rs 13 v/s Rs 28 for Laxopeg - prices of MuOUT would be around Rs 16 as per the company rep
  • Laxopeg claims direct import of raw material from DOW chemicals USA, leading to better product
  • Both Ezlax and Laxopeg are generally well tolerated - Ezlax appears like Fanta (orange drink) while Laxopeg becomes a clear colourless & odourless solution
  • Adding electrolytes does not appear to be clinically indicated in managing chronic constipation - since there is no significant electrolyte loss. It possibly makes sense in the surgical or disimpaction procedures where high doses are needed in adults mostly
  • Adding electrolytes can possibly lead to electrolyte imbalance
  • Adding electrolytes can possibly lead to salty taste, reducing compliance


CLINICAL BOTTOM LINE

  • Low dose PEG is effective, both in the short and long term management of constipation in children.
  • Low dose PEG with or without added electrolytes is safe in the treatment of constipation in children.
  • More studies are needed to determine the most safe and effective form of PEG in children.

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