Expert 2017 Opinion: Miralax is (Still) First Choice Laxative for Children

IJN Koppen et al. Journal of Pediatric Gastroenterology & Nutrition: October 2017 – Volume 65 – Issue 4 – p 361–363

Abstract:

 According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

Because this topic is of great importance to the families that are seen by pediatric gastroenterologists (and pediatricians), I wanted to review this brief article which describes the efficacy and safety of polyethylene glycol (aka miralax).

Key Points:

  • Polyethylene glycol (PEG) is the most widely used laxative in children and adults
  • It works by interacting “with water molecules by forming hydrogen bonds, in a ratio of 100 water molecules per 1 PEG molecule, which leads to an additional increase in colonic water content.” It is minimally absorbed.
  • Studies have demonstrated that PEG is better or noninferior to all of the following: lactulose, milk of magnesia, mineral oil, and flixweed (a medicinal herb)

Safety:

  • Only minor adverse events have been reported in studies.  In randomized, placebo-controlled trials, adverse events “did not occur more frequently in patients receiving PEG compared to patients receiving placebo.”
  • The main safety issue has been when it has been administered via nasogastric administration; improper placement can lead to severe pulmonary complications.  In addition, PEG should be used “cautiously in children with swallowing problems…because of risk of aspiration.”

Combatting Myths: 

  • The authors assert that there has never been reports of physical or psychological dependence.  Weaning from PEG is to prevent relapse of constipation.
  • There is no evidence to support loss of efficacy.
  • The phenomenon of “lazy bowel syndrome” in which there is worsened colonic function has not been described due to PEG; though, patients with underlying motility problems have had these problems misattributed to PEG use.
  • Despite anecdotal reports of tremors, tics, and obsessive-compulsive behavior in children taking PEG, there has been no evidence of a causal relationship.  “These events …are still under investigation, but the FDA has decided that no action is necessary.”  The authors note that the co-occurrence of neuro-behavioral problems and constipation is well-recognized in children with and without laxative use.

Clinical Pearl: Stimulant Laxatives After Repaired Anorectal Malformations:

  • “In children with constipation after repaired anorectal malformations, …stimulant laxatives (eg. senna) should be the laxative of choice.” (J Pediatr Surg 2017; 52: 84-8)

My take (borrowed from the authors): “PEG has rapidly become the treatment of first choice for children with functional constipation.”

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Diagnosis and Misdiagnosis of Constipation

A personal pet peeve is having to explain to so many parents that their child is not constipated.  The typical scenario is that their child went to the ER for abdominal pain and had an abdominal radiograph (AXR); then, the parents are informed that their child is constipated based on ‘fecal loading’ noted on the AXR.  In this scenario, it is common for the child to have the following:

  • regular bowel movements
  • lack of a rectal exam
  • lack of improvement with laxatives (though some do improve, perhaps due to the fact that symptoms often have regression to the mean)
  • often a normal AXR when interpreted by radiologist rather than ED physician (it is normal to have some stool in the colon)

So, I like to see publications that support my viewpoint that this approach is misguided. Two recent studies provide some insight into this topic:

  • SB Freedman et al. J Pediatr 2017; 186: 87-94
  • CC Ferguson et al. Pediatrics 2017; 140 (1):e20162290 (thanks to Ben Gold for this reference)

Freedman et al performed a retrospective cohort study (children <18 yrs) who were diagnosed with constipation at 23 EDs from 2004-2015. This study used the PHIS database. Key findings:

  • 185,439 of 282,225 had AXR at index ED visit
  • Revisits to ED occurred in 3.7%
  • 0.28% returned with a clinically important alternate diagnosis, most commonly appendicitis (34% in this category)
  • Children who had AXR were more likely to have a 3-day revisit with a clinically important alternate diagnosis (0.33% vs. 0.17%)

Recognizing that AXRs are “unnecessary and potentially misleading,” Ferguson et al aimed to decrease AXR utilization in low-acuity patients who were suspected of having constipation. Using quality tools, the authors performed four plan-do-study-act cycles which included holding grand rounds, sharing best practices, metrics reporting, and academic detailing. Key finding:

  • Over 12 months, we observed a significant and sustained decrease from a mean rate of 62% to a mean rate of 24% in the utilizaiton of AXRs in the ED for patients suspected of having constipation.

My take: These studies support my view that routine use of AXR in the diagnosis of constipation is a mistake and can be misleading.

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The Truth about Probiotics: Constipation Version

Families are often surprised to learn my opinion about probiotics.  The “truth” about probiotics is that they are poorly regulated/lack rigorous production standards and are mostly ineffective for many of the conditions for which they have been promoted.  Even in conditions in which there is some effectiveness (eg. antibiotic-associated diarrhea), the number of persons needed to treat for one person to benefit is fairly high.

In addition, when someone says that they are taking a probiotic, many families do not understand the idea of “strain” specific effects.  I tell families that if they see a “dog in yard” sign that they do not know if that is a poodle of a pit bull.  With probiotics, similarly you often do not know if you are getting a pit bull or a poodle.

As a consequence, I think negative studies like a recent report (K Wojtyniak et al. J Pediatr 2017; 184: 101-05) are helpful. In this study, the authors examined the effectiveness of Lactobacillus casei rhamnosus Lcr35 (Lcr35) in the management of constipation.

This randomized, double-blind, placebo-controlled trial was conducted in 94 children <5 years of age. Dose: 8 x10 to the 8th CFU twice daily x 4 weeks.

Key findings:

  • “Lcr35 as a sole treatment was not more effective than placebo in the management of functional constipation.” In fact, the placebo group had a greater increase in bowel movement frequency than the treatment group.
  • Both groups had improvement -more than half in each group (total 52 of 81 who completed study) had reached endpoint of 3 or more BMs/week without soiling.

My take: Probiotics often are ineffective.  This study showed that Lcr35 was NOT helpful for pediatric constipation.

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Claude Monet, La Rue Montorgueil

 

 

FDA Approves Plecanatide (Trulance) for Adults with Idiopathic Constipation

Here’s the link: FDA approves Trulance for Chronic Idiopathic Constipation (Jan 19.2017).  Plecanatide is a guanylate cyclase-C agonist.

An excerpt:

Trulance, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.

The safety and efficacy of Trulance were established in two 12-week, placebo-controlled trials including 1,775 adult participants. Participants were randomly assigned to receive a placebo or Trulance, once daily. Participants in the trials were required to have been diagnosed with constipation at least six months prior to the study onset and to have less than three defecations per week in the previous three months, as well as other symptoms associated with constipation. Participants receiving Trulance were more likely to experience improvement in the frequency of complete spontaneous bowel movements than those receiving placebo, and also had improvements in stool frequency and consistency and straining.

Trulance should not be used in children less than six years of age due to the risk of serious dehydration… The safety and effectiveness of Trulance have not been established in patients less than 18 years of age.

The most common and serious side effects of Trulance was diarrhea.

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Bowel Management Recommendations

A recent “consensus” review on bowel management (G Mosiello et al. JPGN 2017; 64: 343-52) is available as an open access article –Link: Consensus Review of Best Practic of Transanal Irrigation in Children

The use of bowel management tube (or cone) for transanal irrigation has been around since ~1987 (B Shandling et. al. J Ped Surg 1987; 22: 271-3) and generally is considered in children older than 3 years of age with severe problems with defecation (organic and functional).

This particular review has a very good table on troubleshooting (Table 4) and a succinct summary of indications/contraindications (Table 2).

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Here we go again …Miralax Safety Questioned

The issue of miralax safety is something that is discussed on a daily basis in pediatric gastroenterology offices.  It is back in the news.  The headlines suggest that there could be a problem but when one examines these stories we find that these reports have NOT shown data indicating a safety concern.

Here’s a link to a NASPGHAN Neurogastroenterology statement on safety of Miralax:

Here’s a link to a recent article in AJC questioning the safety of Miralax:

In this article, “the FDA told WPVI that there isn’t enough data “to demonstrate a link between PEG 3350 and serious neuropsychiatric issues in children.”

Bayer, MiraLAX’s manufacturer, said in part: “As part of Bayer’s ongoing commitment to consumer well-being, we regularly track, analyze and report all adverse event data related to the use of the product. Results of this ongoing monitoring support the continued safe use of MiraLAX.”

In a 2015 article on Parents.com, Dr. Steve J. Hodges, an associate professor of pediatric urology at the Wake Forest School of Medicine, pointed out that “more than 100 studies have found PEG 3350 is safe to use in children.”

“I have found no published studies linking MiraLAX to severe or harmful side-effects,” said Hodges, who was responding to a New York Times article about the Philadelphia study.”

Here’s a few other posts on Miralax safety:

Related blog posts:

My take (borrowed from expert review): “Generally speaking, if your child has been prescribed PEG 3350 as part of his/her treatment plan, and you feel this medicine provides benefit, you should feel safe continuing PEG 3350. At this time, PEG 3350 appears to be safe based on current medical literature. We recommend discussing any concerns you have about the safety of PEG 3350 with your child’s health care provider. If you would prefer for your child to stop taking PEG 3350, discuss other treatments options with your child’s health care team before stopping PEG 3350 therapy. Although abruptly stopping PEG 3350 is not considered dangerous, it could lead to a relapse/worsening of constipation.”

From 'this week in church signs'

From ‘this week in church signs’

Constipation Video from Primary Children’s Hospital

This is a really good educational video (< 8min) -now on YouTube: Constipation in Children: Understanding and Treating This Common Problem (Thanks to John Pohl’s twitter feed for this resource)

screenshot-78

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