Polyethylene Glycol

Mechanism of Action

PEGs have a variety of molecular weights and are composed of multiple ethylene glycol monomer units that undergo catalysis.[1] PEG is soluble in water and is minimally absorbed in the gastrointestinal tract as a medication. 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. It is available in oral powder packets for single-use (total of 14, 30, and 100 packets in a box) or in a bottle with a measuring cup (119 g, 238 g, 510 g, 527 g, and 765 g container).

• For adult constipation, 17 g of PEG 3350 is mixed in 8 ounces of liquid and taken once daily. The fluid can include water, juice, tea, coffee, or soda. Preliminary data suggests that PEG interacts with starch-based thickeners compared 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 as an over-the-counter medication unless instructed by a physician; if needed more chronically, 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 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 drinks on the day before the procedure. Guidelines also recommend doing split dosing when the colonoscopy is in the afternoon, administering 1 L on the day before the procedure, and 1 L on the day of the procedure.[10]

Specific Patient Population 

• Pregnant Women: It is considered as pregnancy category C medicine. The systemic absorption of PEG is believed to be minimum. Therefore, it is less likely to cause any severe effect on neonates. The American Academy of Family Physicians has reported despite the lack of research on PEG use in pregnancy; it is considered the drug of choice for chronic constipation in pregnant women.
• Breastfeeding Women: There is no specific recommendation for breastfeeding women on the manufacturer label. As previously discussed, PEG has poor systemic absorption, so it should excrete at a low clinical significant level in breast milk.[11]
• Pediatric Patients: 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.[12] 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.[12]
• Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. 
• Patient with Renal Impairment: There is no dose adjustment guidance in the manufacturer label for patients with renal impairment. 
• Geriatric Patients: There is no dose adjustment guidance in the manufacturer label for geriatric patients.

Adverse Effects

Common side effects of oral administration of PEG include flatulence, nausea, stomach cramps, diarrhea, swollen abdomen, and rectal hemorrhage.[13][14]

Urticaria has been observed after using PEG electrolyte lavage solution following topical administration.[9][15]

Acidosis has been reported in literature and case reports with the intravenous administration of drugs utilizing PEG as a vehicle and repeated topical dermal exposure of PEG in burn patients.[16][17]

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.[18] 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 hypersensitivity to polyethylene glycol, 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 monitor for therapeutic efficacy, including decreased abdominal discomfort and pain and bowel movement in 2 to 4 days. Electrolyte imbalances should be monitored periodically with prolonged, frequent, or excessive use.[19] 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 nontoxic, as it is minimally 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, possibly leading to dehydration, especially if water intake is minimal. Dehydration can then result in confusion and potentially seizures.[20] There is no antidote in cases of PEG overdoses. The case that 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 of 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 patient's acidosis.[17]

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. The interprofessional healthcare team should collaboratively discuss alternatives to constipation treatments and 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. Nurses and pharmacists can determine whether the patient is dosing the drug appropriately and also offer suggestions for lifestyle measures to address the issue. This interprofessional approach will yield improved patient results while minimizing adverse events, which are still possible with OTC medication like polyethylene glycol. [Level 5]