PEG 3350 is being prescribed to children in violation of FDA Off-label Use Guidelines
Per FDA’s Off-Label Use Guidelines, “If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.”
1. Prescribed to children in adult doses – In 1999, doctors around the US began prescribing Miralax to children. Of the over 40,000 members of the Parents Against Miralax, Restoralax, Movicol Facebook Group (membership increases daily), most are members whose children were prescribed PEG 3350 laxatives by their doctor, some as young as 2 months old (yet PEG 3350 is not recommended for use by pregnant women). Children are being prescribed adult doses and multiple adult doses per day.
2. Prescribed for long term use – Most parents have had their children prescribed PEG laxatives for longer than the 7 day period recommended on the product label - some of them for years. In addition, label directions say to use just once per day. Doctors are prescribing PEG laxatives to be taken multiple times daily. No research has been done on the effects of long term PEG use in children. High doses of polyethylene glycol can result in hyponatremia, low blood sodium, which causes the body’s cells to swell and can be fatal. Prepubescent children are at higher risk. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1125242/
Regarding lasting effectiveness, this study showed a majority of people who used PEG 3350 required additional constipation treatment interventions after 30 days of PEG 3350 use. http://www.ncbi.nlm.nih.gov/pubmed/16000928
Long term use of polyethylene glycol laxatives can cause dependence on laxatives. Extreme caution is recommended for use in children. http://www.drugs.com/cdi/miralax-powder-for-oral-solution.html
3. Prescribed for chronic constipation – Most of the parents have had their children prescribed PEG laxatives for chronic, rather than occasional constipation. No research has been done on the effects of PEG on patients with chronic constipation.
4. Adverse events records underreported – Whether due to lack of awareness, confusion over the process, or physician discouragement, most consumers do not file adverse event reports. The same is true for doctors. These unreported adverse events cannot be dismissed. According to parents, most prescribing physicians are not reporting to the FDA the polyethylene glycol adverse effects parents have reported to them because they dismiss the connection between adverse events parents are witnessing and use of PEG 3350.
Physician Error Rampant in Off-label Survey
Parents are confused about off-label use of drugs, especially those prescribed to children. They trust their doctors to prescribe treatments that are proven to be safe for children and, after experiencing adverse events, they are shocked to learn that the drug their child has ingested, sometimes in larger than adult doses over long periods of time, is not approved for use in children at all.
Apparently, parents and other consumers are not the only ones confused about off-label prescribing. According to the New York Times, in a 2009 study in Phamacoepidemiology and Drug Safety, a survey of physicians found that many might not even know when they are prescribing off-label. “Of some 600 doctors surveyed, the average physician identified the FDA approval status correctly for only about half the drugs on a list provided by the researchers. Nearly one in five who prescribed Seroqquel (quetiapine) in the previous year thought it was approved for patients with dementia and agitation, even though it was never approved for this use and even carried a ‘black box’ warning that it was dangerous for elderly patients with dementia. And one in three doctors who used lorazepam (often marketed at Ativan) to treat chronic anxiety thought it had been approved for this use; in fact, the FDA warning advises against using it for this purpose. The study’s senior author, Dr. G. Caleb Alexander, assistant professor of medicine at the University of Chicago, said a concern was that off-label uses often did not have the same level of scientific scrutiny as FDA-approved uses.”
http://www.nytimes.com/2009/08/25/health/research/25disp.html
In 2006, Dr. Dean R. Focht outlined highlights of the North American Society for Pediatric Gastroenterology, Hepatology protocol, which includes a 1.5 g/kg of body weight cleanout dose, then 1 g/kg daily maintenance dosage along with behavior recommendations including regular toilet sitting (three times per day) and sticker charts to improve compliance. He claims a 57% “cure” rate with the protocol. Dr. Focht was shocked at doctor lack of awareness, stating that “Some pediatricians thought Miralax could only be used for 2 weeks,” while the product label clearly says not to use for more than 7 days.
http://findarticles.com/p/articles/mi_hb4384/is_12_40/ai_n29314476/
If doctors are not aware that they are prescribing Miralax off-label, or they are aware and are prescribing it regardless, they need to be educated about the adverse events that have been reported to the FDA.
Off-label Prescribing in Neonatal Intensive Care Units
According to this article in the 2005 FDA Science Forum, up to 90% of NICU patients are exposed to drugs that are either unlabeled or used in an off-label manner, including polyethylene glycol.
A New Face on an Old Problem: Excipient Exposure in the Neonatal Intensive Care Unit S. K. McCune, S. Y. Buckman, W. J. Rodriguez, OCTAP, CDER, FDA, Rockville, MD:
"In 1937, sulfanilamide was compounded with diethylene glycol to improve solubility; 107 patients, many of them children, died due to diethylene glycol toxicity. In 1981, the neonatal gasping syndrome secondary to benzyl alcohol toxicity was reported. Extremely low birth weight (ELBW) infants receive significant numbers of medications, putting them at risk for acute and chronic exposure to single or multiple excipients.
A literature review of common excipients led to a focused examination of drug labels for some commonly used drugs in the neonatal intensive care unit (NICU). Also, accepted standards of excipient exposure were examined. Up to 90% of NICU patients are exposed to drugs that are either unlabeled or used in an off-label manner. This study does not endorse the off-label use of these drugs but only examines the potential exposure to excipients during a NICU admission.
Benzyl alcohol, propylene glycol, polyethylene glycol, sodium benzoate, and polysorbate are excipients found in drugs commonly used in the NICU. Aminophylline, Vitamin K, lorazepam, bumetanide, dexamethasone, diazepam, doxapram, pancuronium, phenobarbital, hydrocortisone, methylprednisolone, succinylcholine, enalapril, midazolam and Vitamin E preparations contain benzyl alcohol. Lorazepam, phenytoin, digoxin, MVI-12®, phenobarbital, and diazepam contain propylene glycol. Lorazepam contains polyethylene glycol, diazepam contains sodium benzoate, and MVI® pediatric contains polysorbate. Excipient concentrations and potential exposure will be discussed.
It will be important to document individual neonatal excipient exposures compared to known thresholds. Future trials need to determine the metabolism of excipients in ELBW infants and the potential long-term effects of chronic excipient exposure.”
It is well known in the medical community that a small fraction of adverse events are reported; the FDA cites literature that estimates 1-10%. In Attention must be paid: adverse event reporting needs improvement, the authors write, “ As of 2005, only half of the newly discovered adverse drug reactions were detected and documented within 7 years of drug approval…it takes a median of 11 years to identify a serious adverse drug reaction…it took 81 years to identify aspirin-associated Reye’s Syndrome…Of 33,171 warfarin-associated hospitalizations and 67,200 hemorrhage cases, a reporting rate of 1.07% and 1.02% was calculated (for patients aged 65 or older), respectively. Of 13,363 hospitalizations associated with clopidogrel and ticlopidine, a 0.9% reporting rate was calculated. The 9-year reporting rate for venous thromboembolism associated with thalidomide was calculated to be 2.3%. https://www.openaccessjournals.com/articles/attention-must-be-paid-adverse-event-reporting-needs-improvement.pdf
Some parents tell of being treated disrespectfully by doctors when bringing up the topic of adverse events they say their children have experienced while taking polyethylene glycol products. Doctors are not indicating to parents any knowledge of the FDA Drug Safety Oversight Board Meeting and its findings. This causes parents to wonder what communication is made to ensure that doctors read the public summary issued by the FDA Drug Safety Oversight Board, which warned of potential dangers associated with PEG use in children in 2009.
Per FDA’s Off-Label Use Guidelines, “If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.”
1. Prescribed to children in adult doses – In 1999, doctors around the US began prescribing Miralax to children. Of the over 40,000 members of the Parents Against Miralax, Restoralax, Movicol Facebook Group (membership increases daily), most are members whose children were prescribed PEG 3350 laxatives by their doctor, some as young as 2 months old (yet PEG 3350 is not recommended for use by pregnant women). Children are being prescribed adult doses and multiple adult doses per day.
2. Prescribed for long term use – Most parents have had their children prescribed PEG laxatives for longer than the 7 day period recommended on the product label - some of them for years. In addition, label directions say to use just once per day. Doctors are prescribing PEG laxatives to be taken multiple times daily. No research has been done on the effects of long term PEG use in children. High doses of polyethylene glycol can result in hyponatremia, low blood sodium, which causes the body’s cells to swell and can be fatal. Prepubescent children are at higher risk. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1125242/
Regarding lasting effectiveness, this study showed a majority of people who used PEG 3350 required additional constipation treatment interventions after 30 days of PEG 3350 use. http://www.ncbi.nlm.nih.gov/pubmed/16000928
Long term use of polyethylene glycol laxatives can cause dependence on laxatives. Extreme caution is recommended for use in children. http://www.drugs.com/cdi/miralax-powder-for-oral-solution.html
3. Prescribed for chronic constipation – Most of the parents have had their children prescribed PEG laxatives for chronic, rather than occasional constipation. No research has been done on the effects of PEG on patients with chronic constipation.
4. Adverse events records underreported – Whether due to lack of awareness, confusion over the process, or physician discouragement, most consumers do not file adverse event reports. The same is true for doctors. These unreported adverse events cannot be dismissed. According to parents, most prescribing physicians are not reporting to the FDA the polyethylene glycol adverse effects parents have reported to them because they dismiss the connection between adverse events parents are witnessing and use of PEG 3350.
Physician Error Rampant in Off-label Survey
Parents are confused about off-label use of drugs, especially those prescribed to children. They trust their doctors to prescribe treatments that are proven to be safe for children and, after experiencing adverse events, they are shocked to learn that the drug their child has ingested, sometimes in larger than adult doses over long periods of time, is not approved for use in children at all.
Apparently, parents and other consumers are not the only ones confused about off-label prescribing. According to the New York Times, in a 2009 study in Phamacoepidemiology and Drug Safety, a survey of physicians found that many might not even know when they are prescribing off-label. “Of some 600 doctors surveyed, the average physician identified the FDA approval status correctly for only about half the drugs on a list provided by the researchers. Nearly one in five who prescribed Seroqquel (quetiapine) in the previous year thought it was approved for patients with dementia and agitation, even though it was never approved for this use and even carried a ‘black box’ warning that it was dangerous for elderly patients with dementia. And one in three doctors who used lorazepam (often marketed at Ativan) to treat chronic anxiety thought it had been approved for this use; in fact, the FDA warning advises against using it for this purpose. The study’s senior author, Dr. G. Caleb Alexander, assistant professor of medicine at the University of Chicago, said a concern was that off-label uses often did not have the same level of scientific scrutiny as FDA-approved uses.”
http://www.nytimes.com/2009/08/25/health/research/25disp.html
In 2006, Dr. Dean R. Focht outlined highlights of the North American Society for Pediatric Gastroenterology, Hepatology protocol, which includes a 1.5 g/kg of body weight cleanout dose, then 1 g/kg daily maintenance dosage along with behavior recommendations including regular toilet sitting (three times per day) and sticker charts to improve compliance. He claims a 57% “cure” rate with the protocol. Dr. Focht was shocked at doctor lack of awareness, stating that “Some pediatricians thought Miralax could only be used for 2 weeks,” while the product label clearly says not to use for more than 7 days.
http://findarticles.com/p/articles/mi_hb4384/is_12_40/ai_n29314476/
If doctors are not aware that they are prescribing Miralax off-label, or they are aware and are prescribing it regardless, they need to be educated about the adverse events that have been reported to the FDA.
Off-label Prescribing in Neonatal Intensive Care Units
According to this article in the 2005 FDA Science Forum, up to 90% of NICU patients are exposed to drugs that are either unlabeled or used in an off-label manner, including polyethylene glycol.
A New Face on an Old Problem: Excipient Exposure in the Neonatal Intensive Care Unit S. K. McCune, S. Y. Buckman, W. J. Rodriguez, OCTAP, CDER, FDA, Rockville, MD:
"In 1937, sulfanilamide was compounded with diethylene glycol to improve solubility; 107 patients, many of them children, died due to diethylene glycol toxicity. In 1981, the neonatal gasping syndrome secondary to benzyl alcohol toxicity was reported. Extremely low birth weight (ELBW) infants receive significant numbers of medications, putting them at risk for acute and chronic exposure to single or multiple excipients.
A literature review of common excipients led to a focused examination of drug labels for some commonly used drugs in the neonatal intensive care unit (NICU). Also, accepted standards of excipient exposure were examined. Up to 90% of NICU patients are exposed to drugs that are either unlabeled or used in an off-label manner. This study does not endorse the off-label use of these drugs but only examines the potential exposure to excipients during a NICU admission.
Benzyl alcohol, propylene glycol, polyethylene glycol, sodium benzoate, and polysorbate are excipients found in drugs commonly used in the NICU. Aminophylline, Vitamin K, lorazepam, bumetanide, dexamethasone, diazepam, doxapram, pancuronium, phenobarbital, hydrocortisone, methylprednisolone, succinylcholine, enalapril, midazolam and Vitamin E preparations contain benzyl alcohol. Lorazepam, phenytoin, digoxin, MVI-12®, phenobarbital, and diazepam contain propylene glycol. Lorazepam contains polyethylene glycol, diazepam contains sodium benzoate, and MVI® pediatric contains polysorbate. Excipient concentrations and potential exposure will be discussed.
It will be important to document individual neonatal excipient exposures compared to known thresholds. Future trials need to determine the metabolism of excipients in ELBW infants and the potential long-term effects of chronic excipient exposure.”
It is well known in the medical community that a small fraction of adverse events are reported; the FDA cites literature that estimates 1-10%. In Attention must be paid: adverse event reporting needs improvement, the authors write, “ As of 2005, only half of the newly discovered adverse drug reactions were detected and documented within 7 years of drug approval…it takes a median of 11 years to identify a serious adverse drug reaction…it took 81 years to identify aspirin-associated Reye’s Syndrome…Of 33,171 warfarin-associated hospitalizations and 67,200 hemorrhage cases, a reporting rate of 1.07% and 1.02% was calculated (for patients aged 65 or older), respectively. Of 13,363 hospitalizations associated with clopidogrel and ticlopidine, a 0.9% reporting rate was calculated. The 9-year reporting rate for venous thromboembolism associated with thalidomide was calculated to be 2.3%. https://www.openaccessjournals.com/articles/attention-must-be-paid-adverse-event-reporting-needs-improvement.pdf
Some parents tell of being treated disrespectfully by doctors when bringing up the topic of adverse events they say their children have experienced while taking polyethylene glycol products. Doctors are not indicating to parents any knowledge of the FDA Drug Safety Oversight Board Meeting and its findings. This causes parents to wonder what communication is made to ensure that doctors read the public summary issued by the FDA Drug Safety Oversight Board, which warned of potential dangers associated with PEG use in children in 2009.