PEG-3350, Sodium Chloride, Sodium Bicarbonate and Potassium Chloride

PEG-3350, SODIUM CHLORIDE, SODIUM BICARBONATE AND POTASSIUM CHLORIDE- polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride powder, for solution
Affordable Pharmaceuticals, LLC

1 INDICATIONS AND USAGE

PEG-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 DOSAGE AND ADMINISTRATION

2.1 Dosage Overview

• PEG-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 PEG-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, 1.4 grams of potassium chloride and 2 grams of flavor ingredients.

2.2 Administration Instructions Prior to Dosage

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

1. Take only clear liquids, but avoid red and purple liquids. Patients may consume a light breakfast.
2. Early in the evening prior to colonoscopy, fill the supplied container containing the PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution 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.
3. 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 PEG-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 20-30 mL per minute (1.2 – 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 PEG-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 PEG-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.

3 DOSAGE FORMS AND STRENGTHS

For oral solution: One 4 liter jug with powder for reconstitution with water.

Each 4 liter jug contains: polyethylene glycol 3350 420 g, sodium bicarbonate 5.72 g, sodium chloride 11.2 g, potassium chloride 1.48 g and flavoring ingredients 2 g. 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.

4 CONTRAINDICATIONS

PEG-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 PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution [see How Supplied/Storage and Handling ( 16)]

5 WARNINGS AND PRECAUTIONS

5.1 Serious Fluid and Serum Chemistry Abnormalities

Advise patients to hydrate adequately before, during, and after the use of PEG-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 PEG-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 PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution.

In addition, use caution when prescribing PEG-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 PEG-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 PEG-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 PEG-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 PEG-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 PEG-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 PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution.
Use with caution in patients with severe active ulcerative colitis.