Polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution is indicated for bowel cleansing prior to colonoscopy in adults and pediatric patients aged 6 months or greater.

2.1 Dosage Overview

• Polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, supplied as a powder, must be reconstituted with water before its use; it is not for direct ingestion [see Dosage and Administration (2.2), Warnings and Precautions (5.8)].
• Do not reconstitute with other liquids and/or add starch-based thickeners to the mixing container [see Warnings and Precautions (5.7)].
• The 4 liter reconstituted polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution contains: 420 grams of polyethylene glycol (PEG) 3350, 5.72 grams of sodium bicarbonate, 11.2 grams of sodium chloride, and 1.48 grams of potassium chloride. Besides these, the lemon flavored solution contain flavoring ingredients acesulfame potassium 0.1 gram and flavor lemon 0.4 grams while orange flavored solution contains acesulfame potassium 0.1 gram and flavor orange 0.6 grams respectively.

2.2 Administration Instructions Prior to Dosage

On the day prior to the colonoscopy, instruct patients to:

a) Take only clear liquids, but avoid red and purple liquids. Patients may consume a light breakfast.

b) Early in the evening prior to colonoscopy, fill the supplied container containing the polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution's powder with lukewarm water (to facilitate dissolution) to the 4 liter fill line. The solution is clear and colorless when reconstituted to a final volume of 4 liters.

c) After capping the container, shake vigorously several times to ensure that the ingredients are dissolved. When reconstituted use within 48 hours.

2.3 Dosage

The following is the recommended dose of reconstituted polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for adults and pediatric patients ≥ 6 months. Instruct patients they may consume water or clear liquids during the bowel preparation and after completion of the bowel preparation up until 2 hours before the time of the colonoscopy. The solution is more palatable if chilled prior to administration.

• Adults: Instruct patients to drink a total of up to 4 liters at a rate of 240 mL (8 oz.) every 10 minutes, until 4 liters are consumed or the rectal effluent is clear. Rapid drinking of each portion is preferred to drinking small amounts continuously. For NGT, rate is 20 to 30 mL per minute (1.2 to 1.8 liters per hour).
• Pediatric Patients ≥ 6 Months: Pediatric patients should drink 25 mL/kg/hour until the stool is watery, clear, and free of solid matter. If pediatric patients are unable to drink the reconstituted polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, the solution may be given by nasogastric (NGT). NGT administration is at the rate of 25 mL/kg/hour.

The first bowel movements should occur approximately one hour after the start of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution administration. Continue drinking until the watery stool is clear and free of solid matter.

For oral solution: One 5 liter jug with powder for reconstitution with water.

Each 5 liter jug contains: polyethylene glycol 3350 USP-NF 420 g, sodium bicarbonate USP 5.72 g, sodium chloride USP 11.2 g, potassium chloride USP 1.48 g and flavoring ingredients (acesulfame potassium 0.1 g and flavor lemon 0.4 g for lemon flavor or acesulfame potassium 0.1 gram and flavor orange 0.6 g for orange flavor). When made up to 4 liters volume with water, the solution contains PEG-3350 31.3 mmol/L, sodium 65 mmol/L, chloride 53 mmol/L, bicarbonate 17 mmol/L and potassium 5 mmol/L.

Polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution is contraindicated in the following conditions:

• Gastrointestinal (GI) obstruction, ileus, or gastric retention
• Bowel perforation
• Toxic colitis or toxic megacolon
• Known allergy or hypersensitivity to any component of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution [see How Supplied/Storage and Handling (16)]

5.1 Serious Fluid and Serum Chemistry Abnormalities

Advise patients to hydrate adequately before, during, and after the use of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias, seizures and renal impairment. Fluid and electrolyte abnormalities should be corrected before treatment with polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution.

In addition, use caution when prescribing polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for patients who have conditions, or who are using medications, that increase the risk for fluid and electrolyte disturbances or may increase the risk of adverse events of seizure, arrhythmias, and renal impairment [see Drug Interactions (7.1)].

5.2 Cardiac Arrhythmias

There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Pre-dose and post-colonoscopy ECGs should be considered in patients at increased risk of serious cardiac arrhythmias.

5.3 Seizures

There have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities.

Use caution when prescribing polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for patients with a history of seizures and in patients at increased risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, or patients with known or suspected hyponatremia.

5.4 Renal Impairment

Use caution when prescribing polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for patients with impaired renal function or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs). Advise these patients of the importance of adequate hydration, and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.

5.5 Colonic Mucosal Ulcerations and Ischemic Colitis

Administration of osmotic laxative products may produce colonic mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of stimulant laxatives and polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution may increase this risk. The potential for mucosal ulcerations resulting from the bowel preparation should be considered when interpreting colonoscopy findings in patients with known or suspect inflammatory bowel disease (IBD).

5.6 Use in Patients with Significant Gastrointestinal Disease

If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. If a patient experiences severe bloating, distention or abdominal pain, administration should be slowed or temporarily discontinued until the symptoms abate. If gastrointestinal obstruction or perforation is suspected, appropriate studies should be performed to rule out these conditions before administration of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution.

Use with caution in patients with severe active ulcerative colitis.

5.7 Aspiration

Use with caution in patients with impaired gag reflex, unconscious, or semiconscious patients, and patients prone to regurgitation or aspiration. Such patients should be observed during administration of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, especially if it is administered via nasogastric tube.

Do not combine polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, with starch-based thickeners [see Dosage and Administration (2.1)]. Polyethylene glycol (PEG), a component of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution, when mixed with starch-thickened liquids reduces the viscosity of the starch-thickened liquid. When a PEG-based product used for another indication was mixed in starch-based pre-thickened liquids used in patients with dysphagia, thinning of the liquid occurred and cases of choking and potential aspiration were reported.

5.8 Not for Direct Ingestion

The contents of each jug must be diluted with water to a final volume of 4 liters (4 L) and ingestion of additional water is important to patient tolerance. Direct ingestion of the undissolved powder may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances.

The following serious or otherwise important adverse reactions are described elsewhere in the labeling:

• Serious Fluid and Serum Chemistry Abnormalities [see Warnings and Precautions (5.1)].
• Cardiac Arrhythmias [see Warnings and Precautions (5.2)].
• Seizures [see Warnings and Precautions (5.3)].
• Renal Impairment [see Warnings and Precautions (5.4)]
• Colonic Mucosal Ulcerations, Ischemic Colitis and Ulcerative Colitis [see Warnings and Precautions (5.5)].
• Patients with Significant Gastrointestinal Disease [see Warnings and Precautions (5.6)].
• Aspiration [see Warnings and Precautions (5.7)].
• Direct Ingestion [see Warnings and Precautions (5.8)].

The following adverse reactions have been identified during post-approval use of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nausea, abdominal fullness and bloating are the most common adverse reactions (occurred in up to 50% of patients) to administration of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. Abdominal cramps, vomiting and anal irritation occur less frequently. These adverse reactions are transient and usually subside rapidly. Isolated cases of urticaria, rhinorrhea, dermatitis and (rarely) anaphylactic reaction have been reported which may represent allergic reactions.

Published literature contains isolated reports of serious adverse reactions following the administration of PEG-electrolyte solution products in patients over 60 years of age. These adverse events include upper GI bleeding from Mallory-Weiss Tear, esophageal perforation, asystole, sudden dyspnea with pulmonary edema, and "butterfly-like" infiltrates on chest X-ray after vomiting and aspirating PEG.

7.1 Drugs that May Lead to Fluid and Electrolyte Abnormalities

Use caution when prescribing polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution for patients who are using medications that increase the risk for fluid and electrolyte disturbances or may increase the risk of adverse events of seizure, arrhythmias, and prolonged QT in the setting of fluid and electrolyte abnormalities. Consider additional patient evaluations as appropriate [see Warnings and Precautions (5.1, 5.2, 5.3, and 5.4)] in patients taking these concomitant medications.

7.2 Potential for Altered Drug Absorption

Oral medication administered within one hour of the start of administration of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution may be flushed from the gastrointestinal tract and the medication may not be absorbed properly.

7.3 Stimulant Laxatives

Concurrent use of stimulant laxatives and polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution may increase the risk of mucosal ulceration or ischemic colitis. Avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution.

8.1 Pregnancy

Animal reproduction studies have not been conducted with polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. It is also not known whether polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution in pediatric patients aged 6 months and older is supported by evidence from adequate and well-controlled clinical trials of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution in adults with additional safety and efficacy data from published studies of similar formulations. Use of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution in children younger than 2 years of age should be carefully monitored for occurrence of possible hypoglycemia, as this solution has no caloric substrate. Dehydration has been reported in one child and hypokalemia has been reported in 3 children.

8.5 Geriatric Use

Clinical studies of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

12.1 Mechanism of Action

The primary mode of action is thought to be through the osmotic effect of polyethylene glycol 3350 which causes water to be retained in the colon and produces a watery stool.

12.2 Pharmacodynamics

Polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution induces as diarrhea which rapidly cleanses the bowel, usually within four hours.

12.3 Pharmacokinetics

The pharmacokinetics of PEG 3350 following administration of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution were not assessed. Available pharmacokinetic information for oral PEG 3350 suggests that it is poorly absorbed.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate carcinogenic potential of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution. Studies to evaluate the possible impairment of fertility or mutagenic potential of polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution have not been performed.