Polyethylene Glycol

Article Author:
Amani Dabaja
Article Author:
Ali Dabaja
Article Editor:
Malak Abbas
Updated:
10/20/2020 11:16:48 PM
For CME on this topic:
Polyethylene Glycol CME
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Polyethylene Glycol

Indications

Polyethylene glycol (PEG) is a product with both industrial and pharmaceutical uses. Since many PEG compounds are hydrophilic, industrially, they are utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners.[1]

As a medication, PEG is a part of the laxative class. PEG laxative is safer than the PEG electrolyte lavage solution as there is no salt absorption. FDA approved indications include the treatment of constipation in patients 17 years of age and older. PEG is preferred over other agents for use in chronic constipation and disimpaction as it was associated with limited adverse effects and a better-tasting profile. In a placebo-controlled, blinded, randomized, multicenter, parallel trial N=151, patients were randomly assigned to either receive 17 grams of PEG laxative or dextrose powder placebo daily. The study found PEG to be superior to the placebo. PEG resulted in 4.2 bowel movements versus placebo 2.9 bowel movements (P <0.01) at the end of week 1 and 4.5 versus 2.7 bowel movements, respectively (p<0.001), at the end of week 2. Overall, PEG was associated with less cramping, better stool consistency, and passage (p<0.001) in comparison to placebo dextrose. [2] There were also no significant differences in laboratory changes between the two groups.[2] Another randomized, placebo-controlled, multicenter, double-blind trial assessed PEG 3350 over a 7-day period and included a total of 203 patients. Patients in the group receiving PEG 3350 versus placebo preferred PEG as they reported less hardened stools and decreased exertion (P < 0.0001). The patients in the PEG group also proclaimed a better quality of life, reduced pain, less bloating, and alleviation of constipation symptoms.[3]

Non-FDA approved indications include colonoscopy preparation, fecal impaction, chronic constipation, and constipation in pediatric patients. A double-blind, placebo-controlled, parallel-group study assessed the safety of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) over six months in N=70 patients with chronic constipation. The study found that over 20 weeks, the dosage decreased progressively, and there was a 77% complete reduction of constipation symptoms in PMF-100 versus 20% in placebo-controlled group.[4] Furthermore, there were no significant differences in adverse events between the two groups. Another multicenter, randomized, double-blind, parallel study assessed PEG 4000 versus lactulose in N=96 pediatric patients aged between 6 months to 3 years for 3-months. The study concluded that PEG vs. lactulose had comparable efficacy if not better and long-term tolerance. Researchers noted that children in the lactulose group had worsened vomiting and flatulence in comparison to the PEG 4000 group. There were also no qualitative or quantitative treatment-related differences in laboratory values including, electrolytes, total protein, albumin, vitamin A, D and folates, and serum iron.[5]

Mechanism of Action

PEGs have a variety of molecular weights and are composed of multiple ethylene glycol monomer units that undergo catalysis.[1]

As a medication, PEG is soluble in water and is not reabsorbed in the gastrointestinal tract. PEG forms hydrogen bonds with water molecules. For this reason, it can prevent the reabsorption of water, which causes water retention in the stool and increases the osmotic pressure. As a result, the stool softens, and bowel movements occur more frequently.[6][7]

Administration

Polyethylene glycol 3350 is available as a powder for solution. The preparation is usually for oral intake. For adult constipation, 17 g of PEG 3350 is mixed in 8 ounces of liquid and taken once daily. The liquid can include water, juice, tea, coffee, or soda. Preliminary data suggests that PEG interacts with starch-based thickeners in comparison to xanthan gum thickeners. If using starch-thickened liquids for the mixture, there could be a loss of viscosity; this is relevant for patients who require thickened liquids to prevent aspiration. In these cases, an alternative (xanthan gum-based) thickening agent or alternative laxative is the recommended therapy.[8] In the adult population, PEG should not be used for more than two weeks at a time as an over the counter medication unless instructed by a physician; if it is needed more chronically, then it can be taken for up to 6 months.[9] Of note, the onset of the initial response to PEG can range from 2 to 4 days for a patient to experience a bowel movement.[7]

In children greater than two years of age, the guidelines recommend that for fecal impaction, the dose is 1 to 1.5 g/kg/day for 3 to 6 days, with a maximum of 6 consecutive days.[10] In more chronic constipation cases, the initial dosing is 0.4 mg/kg/day orally; then, maintenance dosing is 0.2 to 0.8 mg/kg/day adjusted to response. The recommendation is to continue for at least two months and discontinue gradually once symptoms resolve for at least a month.[10]

In preparation for a colonoscopy PEG is used to cleanse the bowel to help provide a clear image of the mucosa. PEG is administered by mixing 238 grams in 2 Liters (L) sports drink on the day before the procedure. Guidelines also recommend doing split dosing when the colonoscopy is in the afternoon, administering 1 L day before the procedure, and 1 L on the day of the procedure.[11]

Adverse Effects

Common side effects of oral administration of PEG include flatulence, nausea, stomach cramps, diarrhea, swollen abdomen, and rectal hemorrhage.[12][13] Urticaria has been observed after the use of PEG electrolyte lavage solution following topical administration.[9][14]

Acidosis has been reported in literature and case reports with the intravenous administration of drugs utilizing PEG as a vehicle, as well as repeated topical dermal exposure of PEG in burn patients.[15][16] The case which has reported metabolic acidosis included a 34-year-old female who presented with acute respiratory failure and showed metabolic anion-gap acidosis, which worsened after four days of treatment. The patient was sedated with intravenous lorazepam with doses up to 30 milligrams per hour, which contained PEG-400 in propylene glycol with 2% benzyl alcohol. PEG, which is oxidized by alcohol dehydrogenase to hydroxy acid and acid metabolites, was a potential contributor to the acidosis.[16]

Furthermore, some cases have shown renal proximal tubular necrosis with oliguria, azotemia, and renal failure following intravenous administration of PEG and topical application in burn patients.[17] Of note, most of the cases were from more than 20 years ago.

In the pediatric population, the FDA has received reports of seizures, tremors, obsessive-compulsive behaviors (including repetitive chewing and sucking), paranoia and mood swings, tics, headache, sedation, aggression, anxiety, lethargy, and rages with the prolonged use of PEG.  

Contraindications

PEG is contraindicated in patients with known or suspected bowel obstruction, appendicitis, inflamed bowel disease, perforated bowel, and patients with hypersensitivity to polyethylene glycol or any component of the formulation.

Precautionary measures are necessary for patients with electrolyte imbalances and patients with renal impairment.[9]

Monitoring

Patients should have an assessment for signs and symptoms of bowel obstruction before the initiation of treatment. Patients should also receive instruction on the proper use of PEG and to monitor for therapeutic efficacy, including decreased abdominal discomfort and pain and bowel movement in 2 to 4 days. Electrolyte imbalances should also have monitoring with prolonged, frequent, or excessive use.[18] Pediatric patients on long-term use of PEG should also be monitored for neuropsychiatric events.

Patients should discontinue the use of PEG if they experience loose stools. Furthermore, clinicians should taper down patients on chronic therapy.

Toxicity

Exposure to PEG is uncommon, and toxicity is very rare. PEG with high and intermediate molecular weight is considered to be nontoxic, as it is not absorbed following oral ingestion. Case studies have reported that prolonged use of IV infusions containing PEG as a vehicle, massive ingestion of PEG, and prolonged application of low-weight PEG products have correlations with renal injury and metabolic acidosis. Patient overdoses of PEG can cause diarrhea, which may lead to dehydration, especially if water intake is minimal. Dehydration can then result in confusion and potentially seizures.[19] There is no antidote in cases of PEG overdoses.

Enhancing Healthcare Team Outcomes

Polyethylene glycol is an over the counter medication, as such there is increased access to the drug. Healthcare providers need to emphasize directions for use and misuse. Patients should be counseled on the onset of action of medication as well as when to discontinue PEG. Primary teams should work collaboratively to discuss alternatives for treatments of constipation and also incorporate lifestyle modifications with treatments. Nutritionists and nurses can play a role in educating patients on a highly nutritious fibrous diet and increased fluid intake to help with bowel movements.


References

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[3] McGraw T, Polyethylene glycol 3350 in occasional constipation: A one-week, randomized, placebo-controlled, double-blind trial. World journal of gastrointestinal pharmacology and therapeutics. 2016 May 6;     [PubMed PMID: 27158544]
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