Parental concerns over MiraLAX laxative continue to spur closer review

Constipation is a relatively common problem in pediatric practice, with reported prevalence rates between 1% and 30%, as well as the chief complaint in 3% to 5% of visits to pediatric outpatient clinics. Because most constipation cases can be remedied through recommended over-the-counter laxatives, constipation is rarely a cause for severe worry among parents.

However, one commonly prescribed laxative medication, MiraLAX, has been the focus of significant parental apprehension due to concerns that its active ingredient, polyethylene glycol 3350 (PEG 3350), may be linked to tremors, tics, obsessive-compulsive behaviors and aggression in children following its use.

William Gerson
William T. Gerson

“Understanding risk in terms of pharmaceutical agents is complicated,” William T. Gerson, MD, clinical professor of pediatrics at the University of Vermont College of Medicine, told Infectious Diseases in Children. “Rare complications might not appear until after medications are in widespread use and are expected even when not seen in clinical trials as both a function of statistics number of patients studied in clinical trials can never uncover truly rare events and the fact that clinical trials typically limit the patient population studied, leaving out patients with preexisting diseases.”

To voice their concerns, many parents of children exhibiting neuropsychiatric symptoms after using MiraLAX have joined activist groups, most notably the private Facebook group Parents Against MiraLAX (PEG 3350), which now boasts more than 12,000 members.

“We are a group of parents and family members who are against PEG 3350 and are here to discuss its cons. We discuss alternative options and ways to talk to doctors about our opposition to this very dangerous drug,” Parents Against MiraLAX (PEG 3350) claim on their Facebook group. “We are not a replacement for the type of health care you choose, we only speak from experience. You have to make your own choices and decisions based on your child and research.”

Primarily recommended for short-term use to treat occasional constipation or irregular bowel movements, MiraLAX is not approved for long-term use in adults nor pediatric use by the FDA, yet it is commonly prescribed for children, a fact that has given rise to much of the public outcry surrounding its possible link to adverse neuropsychiatric events.

“Although PEG 3350 is commonly used as an osmotic laxative agent to treat constipation in children, it is not labeled by the FDA for use below 17 years of age,” Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences and Blank Children’s Hospital and Clinics, told Infectious Diseases in Children. “However, PEG 3350 has been recommended as a first-line laxative for children in guidelines published in 2014, as its efficacy is well supported by published studies in children.”

Initial consumer skepticism of MiraLAX originated in 2012, following a citizen petition by the Empire State Consumer Project urging the FDA to investigate the long-term effects of PEG 3350 for long- and short-term use. The petition also called for immediate recall of products containing the ingredient, so a black box warning could be added as well as review and disclosure of all clinical trial results concerning PEG 3350.

Edward A. Bell, PharmD, BCPS
Edward A. Bell

In 2014, the request received partial acceptance and partial denial, claiming that the adverse effects demonstrated in the petition were insufficient to implement a boxed warning. In addition, the FDA was not aware of any unpublished clinical trials, and the reported adverse effects did not warrant additional studies on long- and short-term use.

“In response to the citizen’s petition, the FDA carefully evaluated published studies and reports in the FDA’s Adverse Effect Reporting System, concluding that PEG 3350 products are safe and effective, and a change to the product’s labeling is not required at this time,” Bell said.

Despite denials of imminent harm to children, the FDA agreed with the petition’s claim that data concerning the safety and effectiveness of PEG 3350 in children do not exist. This lack of information prompted the administration to fund studies regarding the exposure of children to PEG 3350 and its degradants: ethylene glycol and diethylene glycol.

“Constipation, along with chronic gastrointestinal complaints, have been the focus of enormous attention over the last several decades,” Gerson said. “The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and international pediatric gastrointestinal organizations have made a priority of applying serious academic attention to common pediatric gastrointestinal conditions. They have led the way on establishing criteria and promoting guidelines for management available to all practitioners that are reasoned and sound. However, there remains a paucity of randomized control trials of efficacy let alone safety, which is acknowledged by all.”

To fill this knowledge gap and examine the long-term effects of MiraLAX, researchers at the Children’s Hospital of Philadelphia have been conducting FDA-grant funded study analyzing the effects of PEG 3350 among children who have received medications containing the ingredient for at least 1 month.

Patients included in the CHOP study have been split into three categories, including those who are constipated but otherwise healthy, those with gastrointestinal concerns like Crohn’s or celiac disease and those with preexisting neurological concerns, such as cerebral palsy; a control group of children who have not received PEG 3350-containing medication will also be included in the study. 

“This study in enrolling children who are chronically treated with PEG 3350 for constipation, and will entail blood sampling for additional analysis of the pharmacokinetics of ethylene glycol and diethylene glycol,” Bell said. “With the conclusion of the ongoing study, additional information should become available to allow further analysis of the safety of PEG 3350 use in children.”

Although researchers at CHOP were unable to comment on an ongoing study, which would need to be first submitted to the FDA for review, Gerson recommended that pediatricians not change their current practice until the results of the CHOP study are available.

Gerson also noted that despite the various alternative medications available to treat pediatric constipation including other laxatives, stool softeners, mineral oil, sucralose and lactulose recent constipation guidelines have switched to using MiraLAX to the point that the medication is commonly known as “vitamin M” for its ease of use, general effectiveness and accepted safety.

“One needs to remember that, unfortunately, children can rarely have the sudden onset of disturbing symptoms,” Gerson said. “Given the common use of MiraLAX, chance association is likely to occur; that by no means is meant to infer that there are not rare complications or that the use of MiraLAX is appropriate in all situations. However, there are no data to support a change in practice at this time and alternative treatments are not necessarily safer.” —Katherine Bortz and Bob Stott

Constipation is a relatively common problem in pediatric practice, with reported prevalence rates between 1% and 30%, as well as the chief complaint in 3% to 5% of visits to pediatric outpatient clinics. Because most constipation cases can be remedied through recommended over-the-counter laxatives, constipation is rarely a cause for severe worry among parents.

However, one commonly prescribed laxative medication, MiraLAX, has been the focus of significant parental apprehension due to concerns that its active ingredient, polyethylene glycol 3350 (PEG 3350), may be linked to tremors, tics, obsessive-compulsive behaviors and aggression in children following its use.

William Gerson
William T. Gerson

“Understanding risk in terms of pharmaceutical agents is complicated,” William T. Gerson, MD, clinical professor of pediatrics at the University of Vermont College of Medicine, told Infectious Diseases in Children. “Rare complications might not appear until after medications are in widespread use and are expected even when not seen in clinical trials as both a function of statistics number of patients studied in clinical trials can never uncover truly rare events and the fact that clinical trials typically limit the patient population studied, leaving out patients with preexisting diseases.”

To voice their concerns, many parents of children exhibiting neuropsychiatric symptoms after using MiraLAX have joined activist groups, most notably the private Facebook group Parents Against MiraLAX (PEG 3350), which now boasts more than 12,000 members.

“We are a group of parents and family members who are against PEG 3350 and are here to discuss its cons. We discuss alternative options and ways to talk to doctors about our opposition to this very dangerous drug,” Parents Against MiraLAX (PEG 3350) claim on their Facebook group. “We are not a replacement for the type of health care you choose, we only speak from experience. You have to make your own choices and decisions based on your child and research.”

Primarily recommended for short-term use to treat occasional constipation or irregular bowel movements, MiraLAX is not approved for long-term use in adults nor pediatric use by the FDA, yet it is commonly prescribed for children, a fact that has given rise to much of the public outcry surrounding its possible link to adverse neuropsychiatric events.

“Although PEG 3350 is commonly used as an osmotic laxative agent to treat constipation in children, it is not labeled by the FDA for use below 17 years of age,” Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences and Blank Children’s Hospital and Clinics, told Infectious Diseases in Children. “However, PEG 3350 has been recommended as a first-line laxative for children in guidelines published in 2014, as its efficacy is well supported by published studies in children.”

Initial consumer skepticism of MiraLAX originated in 2012, following a citizen petition by the Empire State Consumer Project urging the FDA to investigate the long-term effects of PEG 3350 for long- and short-term use. The petition also called for immediate recall of products containing the ingredient, so a black box warning could be added as well as review and disclosure of all clinical trial results concerning PEG 3350.

Edward A. Bell, PharmD, BCPS
Edward A. Bell

In 2014, the request received partial acceptance and partial denial, claiming that the adverse effects demonstrated in the petition were insufficient to implement a boxed warning. In addition, the FDA was not aware of any unpublished clinical trials, and the reported adverse effects did not warrant additional studies on long- and short-term use.

“In response to the citizen’s petition, the FDA carefully evaluated published studies and reports in the FDA’s Adverse Effect Reporting System, concluding that PEG 3350 products are safe and effective, and a change to the product’s labeling is not required at this time,” Bell said.

Despite denials of imminent harm to children, the FDA agreed with the petition’s claim that data concerning the safety and effectiveness of PEG 3350 in children do not exist. This lack of information prompted the administration to fund studies regarding the exposure of children to PEG 3350 and its degradants: ethylene glycol and diethylene glycol.

“Constipation, along with chronic gastrointestinal complaints, have been the focus of enormous attention over the last several decades,” Gerson said. “The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and international pediatric gastrointestinal organizations have made a priority of applying serious academic attention to common pediatric gastrointestinal conditions. They have led the way on establishing criteria and promoting guidelines for management available to all practitioners that are reasoned and sound. However, there remains a paucity of randomized control trials of efficacy let alone safety, which is acknowledged by all.”

To fill this knowledge gap and examine the long-term effects of MiraLAX, researchers at the Children’s Hospital of Philadelphia have been conducting FDA-grant funded study analyzing the effects of PEG 3350 among children who have received medications containing the ingredient for at least 1 month.

Patients included in the CHOP study have been split into three categories, including those who are constipated but otherwise healthy, those with gastrointestinal concerns like Crohn’s or celiac disease and those with preexisting neurological concerns, such as cerebral palsy; a control group of children who have not received PEG 3350-containing medication will also be included in the study. 

“This study in enrolling children who are chronically treated with PEG 3350 for constipation, and will entail blood sampling for additional analysis of the pharmacokinetics of ethylene glycol and diethylene glycol,” Bell said. “With the conclusion of the ongoing study, additional information should become available to allow further analysis of the safety of PEG 3350 use in children.”

Although researchers at CHOP were unable to comment on an ongoing study, which would need to be first submitted to the FDA for review, Gerson recommended that pediatricians not change their current practice until the results of the CHOP study are available.

Gerson also noted that despite the various alternative medications available to treat pediatric constipation including other laxatives, stool softeners, mineral oil, sucralose and lactulose recent constipation guidelines have switched to using MiraLAX to the point that the medication is commonly known as “vitamin M” for its ease of use, general effectiveness and accepted safety.

“One needs to remember that, unfortunately, children can rarely have the sudden onset of disturbing symptoms,” Gerson said. “Given the common use of MiraLAX, chance association is likely to occur; that by no means is meant to infer that there are not rare complications or that the use of MiraLAX is appropriate in all situations. However, there are no data to support a change in practice at this time and alternative treatments are not necessarily safer.” —Katherine Bortz and Bob Stott