At Issue

Science, Concerns Behind the MiraLAX Laxative Debate

Polyethylene glycol or PEG 3350 — commonly known as MiraLAX by Bayer — has been in the news during the past few years due to the concern for potential side effects in children, most notably undesirable behavioral changes. Although the FDA has not approved long-term use of PEG 3350 in children aged younger than 17 years, the laxative is used off-label widely in clinical practice.

Ashish S. Chogle

There are lack of data to support this off-label use of PEG 3350 for the long-term management of childhood constipation because most studies have only measured short-term outcomes; as such, the term ‘off-label’ does not imply an improper, illegal, contraindicated or investigational use. Pediatricians often have to exercise their professional judgement based on the best available research and anecdotal evidence to recommend medications that do not have FDA approval for use in children.

Theoretically, PEG 3350 is a polymer that is too big to be absorbed by the intestine. When PEG 3350 is consumed, it remains in the gut and holds water. This hydrated PEG 3350 is then excreted by the patient and not retained in any form. Data from pediatric studies have shown PEG 3350 to be more effective at improving the frequency of defecation in children with chronic constipation compared with placebo and other agents, such as lactulose, Phillip’s Milk of Magnesia (magnesium hydroxide, Bayer) or mineral oil. PEG 3350 also appears to have a good safety profile as per these studies, with minor adverse events that are less prevalent than other laxative agents, including abdominal pain, nausea, vomiting, gassiness, bloating, and diarrhea. However, no neuropsychiatric side effects have been documented in these studies.

Within the past few years, the FDA has received several reports of adverse events including neuropsychiatric symptoms in children taking PEG 3350, which include tics, anxiety, rage, paranoia, phobias, mood swings and depression. The exact incidence of these neuropsychiatric symptoms in patients being treated with PEG 3350 for functional constipation is not known, and, because the reported adverse events are extremely vague, it is difficult to establish causality with PEG 3350 based solely on these reports.

There are several confounding factors that could influence development of the reported symptoms, including underlying diagnoses such as autism, behavioral disorders, concurrent medications and comorbidities. Possible links between PEG 3350 use and adverse events in children include the absorption of the low-molecular-weight byproducts of PEG 3350 or that absorption of PEG 3350 in children is greater than in adults, especially among constipated patients. Another possible etiology for these safety concerns is that PEG products may be degraded before ingestion if parents premix the product and store in suspension form for a prolonged period; further, some children may be more susceptible to adverse effects of PEG 3350, especially when high doses are given or following prolonged use.

A multicenter research group, including the Children’s Hospital of Orange County, is currently studying the FDA adverse event reports database for MiraLAX, while also surveying pediatric gastroenterologists to obtain an estimate of the parent-reported symptoms and physician experience. Additionally, the Children’s Hospital of Philadelphia (CHOP) is currently conducting an NIH-funded study that will check for presence of byproducts of PEG 3350, specifically ethylene glycol and diethylene glycol in the blood of children on PEG 3350.

I believe the jury is still out on whether to use MiraLAX in children. Unless adverse data emerge from the studies from CHOP or our own research group, current evidence and physician experience support the use of PEG 3350 to treat constipation in children. However, understandably, if parents are reluctant to have their children started or continued on MiraLAX, physicians can certainly offer alternatives, such as magnesium hydroxide, lactulose or mineral oil, in addition to behavioral modification and dietary changes to include more fiber, fluids and probiotics.

Disclosure: Chogle reports no relevant financial disclosures.

Polyethylene glycol or PEG 3350 — commonly known as MiraLAX by Bayer — has been in the news during the past few years due to the concern for potential side effects in children, most notably undesirable behavioral changes. Although the FDA has not approved long-term use of PEG 3350 in children aged younger than 17 years, the laxative is used off-label widely in clinical practice.

Ashish S. Chogle

There are lack of data to support this off-label use of PEG 3350 for the long-term management of childhood constipation because most studies have only measured short-term outcomes; as such, the term ‘off-label’ does not imply an improper, illegal, contraindicated or investigational use. Pediatricians often have to exercise their professional judgement based on the best available research and anecdotal evidence to recommend medications that do not have FDA approval for use in children.

Theoretically, PEG 3350 is a polymer that is too big to be absorbed by the intestine. When PEG 3350 is consumed, it remains in the gut and holds water. This hydrated PEG 3350 is then excreted by the patient and not retained in any form. Data from pediatric studies have shown PEG 3350 to be more effective at improving the frequency of defecation in children with chronic constipation compared with placebo and other agents, such as lactulose, Phillip’s Milk of Magnesia (magnesium hydroxide, Bayer) or mineral oil. PEG 3350 also appears to have a good safety profile as per these studies, with minor adverse events that are less prevalent than other laxative agents, including abdominal pain, nausea, vomiting, gassiness, bloating, and diarrhea. However, no neuropsychiatric side effects have been documented in these studies.

Within the past few years, the FDA has received several reports of adverse events including neuropsychiatric symptoms in children taking PEG 3350, which include tics, anxiety, rage, paranoia, phobias, mood swings and depression. The exact incidence of these neuropsychiatric symptoms in patients being treated with PEG 3350 for functional constipation is not known, and, because the reported adverse events are extremely vague, it is difficult to establish causality with PEG 3350 based solely on these reports.

There are several confounding factors that could influence development of the reported symptoms, including underlying diagnoses such as autism, behavioral disorders, concurrent medications and comorbidities. Possible links between PEG 3350 use and adverse events in children include the absorption of the low-molecular-weight byproducts of PEG 3350 or that absorption of PEG 3350 in children is greater than in adults, especially among constipated patients. Another possible etiology for these safety concerns is that PEG products may be degraded before ingestion if parents premix the product and store in suspension form for a prolonged period; further, some children may be more susceptible to adverse effects of PEG 3350, especially when high doses are given or following prolonged use.

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A multicenter research group, including the Children’s Hospital of Orange County, is currently studying the FDA adverse event reports database for MiraLAX, while also surveying pediatric gastroenterologists to obtain an estimate of the parent-reported symptoms and physician experience. Additionally, the Children’s Hospital of Philadelphia (CHOP) is currently conducting an NIH-funded study that will check for presence of byproducts of PEG 3350, specifically ethylene glycol and diethylene glycol in the blood of children on PEG 3350.

I believe the jury is still out on whether to use MiraLAX in children. Unless adverse data emerge from the studies from CHOP or our own research group, current evidence and physician experience support the use of PEG 3350 to treat constipation in children. However, understandably, if parents are reluctant to have their children started or continued on MiraLAX, physicians can certainly offer alternatives, such as magnesium hydroxide, lactulose or mineral oil, in addition to behavioral modification and dietary changes to include more fiber, fluids and probiotics.

Disclosure: Chogle reports no relevant financial disclosures.