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’

Prucalopride -Not Better Than Placebo for Children with Constipation

Background: There were high expectations for prucalopride for the treatment of constipation based on previous small studies as well as a placebo-controlled trial in adults.  In adults, after 12 weeks of treatment, between 19.5-29% were responders compared to 9.6-12.1% in placebo patients. Prucalopride is a 5-hydroxytryptamine receptor-4  (5HT4) agonist which has been shown to accelerate colonic motility and is similar structurally to agents like cisapride and tegaserod; these latter medications have shown effectiveness as prokinetics but were limited by life-threatening cardiovascular side effects.

Design: Large (n=213), multicenter, placebo-controlled trial (Mugie SM, et al. Gastroenterol 2014; 147: 1285-95, editorial 1214-16). Response to medication indicated by >3 spontaneous bowel movements per week and <1 episode of fecal incontinence every 2 weeks.

Findings:

  • 17% of prucalopride subjects and 17.8% of placebo subjects were considered responders.
  • If based solely on bowel movement frequency, 29.2% of prucalopride achieved >3 BMs/week, whereas 35.5% of placebo-treated patients achieved this frequency.
  • Adverse effects were similar

Why did Prucalopride not work?

The authors and editorial make several speculations.  In children, withholding behavior is much more important in the pathophysiology of functional constipation (FC) than in adults.  In addition, slow transit constipation is much more common in adults than in children. In the adolescents (≥12 to <18) there was a mild response noted: 18.5% compared with 14.8% of placebo-treated patients (P=.38). The editorial notes that the short length of the trial (8 weeks) could explain the negative results, though this is unlikely.

The editorial, by Samuel Nurko and Miguel Saps, notes a much higher response to polyethylene glycol which “is the mainstay of treatment.”  “PEG-based solutions achieved a successful outcome in 56% of participants compared with 29% in the lactulose group.”

Take-home message: “This study does not provide new data to justify a change in the indication of PEG as first line of treatment for FC in children.”

In followup to questions regarding Miralax safety, here is a link from NASPGHAN’s Neurogastroenterology and Motility Committee: Miralax FAQ

Related blog posts:

A Sign in Our Office --Needs Clarification

A Sign in Our Office –Needs Clarification

Miralax -More Scrutiny, Research Study

A recent NY Times article is probably ‘required reading’ for all pediatric gastroenterologists, pediatricians, and family practitioners:

Here’s the link: Mirlax -Scrutiny for a Childhood Remedy

Here are some excerpts:

The [FDA] agency has asked a team of scientists in Philadelphia to look more closely at the active ingredient in Miralax and similar generic products, called polyethylene glycol 3350, or PEG 3350. While outlining the scope of the research, the agency also disclosed that its scientists had discovered trace amounts of two potential toxins in batches of Miralax tested six years ago.

The news is likely to surprise parents and some doctors.

“Every pediatric GI physician, I would guarantee you, has told a family this is a safe product,” said Dr. Kent C. Williams, a gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio. Now, he worries, “it may not be true.”

Doctors have long recommended these laxatives for their convenience and on the grounds that very little PEG 3350 is absorbed in the intestines. But the F.D.A. says there is little data on its absorption in children, especially the very young and chronically constipated. The agency never approved long-term daily use of the laxatives, even in adults….

Moreover, for years the F.D.A. has received occasional reports of tremors, tics and obsessive-compulsive behavior in children given laxatives containing PEG 3350. It is not known whether the laxatives are the cause….

The F.D.A. said that it had tested eight batches of Miralax and found tiny amounts of ethylene glycol (EG) and diethylene glycol (DEG), ingredients in antifreeze, in all of them. The agency said the toxins were impurities resulting from the manufacturing process.

Those tests were conducted in 2008..The agency again tested PEG 3350 laxatives from five makers in 2013, Mr. Ventura said. None had detectable amounts of EG or DEG. “The amounts were so low,” he added, and “complied with internationally recognized safety standards.”

Bottomline: The previous pediatric studies of Miralax that have been published have shown favorable benefits and not disclosed adverse effects.  It is difficult to exclude the possibility that there is a small subset of children in which Miralax results in adverse effects.  As with many medications, more pediatric data is needed.

Question: Will this or should this change how Miralax is discussed with families?

Related blog posts: