Polyethylene Glycol 3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Ascorbic Acid, and Sodium Ascorbate Package Insert

1 INDICATIONS AND USAGE

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults.

2 DOSAGE AND ADMINISTRATION

2.1 Important Preparation and Administration Instructions

• Correct fluid and electrolyte abnormalities before treatment with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution [see Warnings and Precautions (5.1)].
• Two doses of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution are required for a complete preparation for colonoscopy. The time interval between the two doses depends on the regimen prescribed and the planned timing of the colonoscopy procedure. [see Dosage and Administration (2.2, 2.3 )].
• The “Split-Dose” is the preferred method and consists of two separate doses: the first dose is taken the evening before the colonoscopy, and the second dose is taken the next day, the morning of the day of the colonoscopy [see Dosage and Administration (2.2)].
• The “Evening Only” is the alternative method and consists of two separate doses: both doses are taken in the evening before the day of the colonoscopy, with a minimum of 1.5 hours between the start of the first dose and the start of the second dose [see Dosage and Administration (2.3)].
• Both Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution dosing regimens require administration of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution using the mixing container provided to reconstitute the contents of Pouch A and B with water to the Fill Line. Do not reconstitute with other liquids and/or add starch-based thickeners to the mixing container [see Warnings and Precautions (5.7)].
• Additional clear liquids (including water) must be consumed in both dosing regimens [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
• Consume only clear liquids (no solid food) from the start of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution treatment until after the colonoscopy.
• Do not eat or drink alcohol, milk, anything colored red or purple or any other foods containing pulp material.
• Do not take other laxatives while taking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution [see Drug Interactions (7.3)].
• Do not take oral medications within 1 hour before or after starting each dose of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution [see Drug Interactions (7.2)].
• Ensure completion of Dose 2, including all additional liquids, at least 2 hours before the colonoscopy.
• Storage: After reconstitution, store Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution in an upright position and keep refrigerated. Use within 24 hours after it is mixed in water.

2.2 Two-Day Split-Dosing Regimen (Preferred Method)

The Two-Day Split-Dosing regimen is the preferred dosing method.

Instruct adult patients that on the day before the clinical procedure, they can consume breakfast, followed by a light lunch (no solid foods), and clear soup and/or plain yogurt for dinner, which must be completed at least 1 hour prior to the start of the first Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution dose.

Instruct adult patients to take two separate doses in conjunction with fluids as follows:

Dose 1 – In the evening before the colonoscopy, approximately 10 to 12 hours before Dose 2:

1. 1. Empty the contents of 1 Pouch A and 1 Pouch B into the mixing container that comes with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
2. 2. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
3. 3. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A and B are completely dissolved.
4. 4. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all the solution.
5. 5. Refill the mixing container halfway to the Fill Line (at least 16 ounces) with a clear liquid and drink all this liquid before going to bed.

Dose 2 – Take next morning, on the day of the colonoscopy, approximately 12 hours after the start of Dose 1 and at least 3 ½ hours prior to colonoscopy:

1. 1. Empty the contents of 1 Pouch A and 1 Pouch B into the mixing container that comes with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
2. 2. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
3. 3. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A and B are completely dissolved.
4. 4. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all of the solution.
5. 5. Refill the mixing container halfway to the Fill Line (at least 16 ounces) with a clear liquid and drink all this liquid at least 2 hours before the colonoscopy.
6. 6. Consume additional water or clear liquids up to 2 hours before the colonoscopy or as prescribed by your healthcare provider. Then stop drinking liquids until after the colonoscopy.

Stop drinking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution temporarily or drink each portion at longer intervals if severe bloating, abdominal discomfort or distention occurs, until these symptoms resolve.

2.3 One-Day Evening Only Dosing Regimen (Alternative Method)

The One-Day Evening Only regimen is the alternative dosing method for patients for whom the Split-Dosing regimen is inappropriate.

Instruct adult patients that on the day before the clinical procedure, they can consume breakfast, followed by a light lunch (no solid foods), and clear soup and/or plain yogurt for dinner, which must be completed at least 1 hour prior to the start of the first Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution dose.

Instruct adult patients to take two separate doses in conjunction with fluids as follows:

Dose 1 – At least 3 ½ hours before bedtime the evening before the colonoscopy:

1. 1. Empty the contents of 1 Pouch A and 1 Pouch B into the mixing container that comes with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
2. 2. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
3. 3. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A and B are completely dissolved.
4. 4. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all the solution.

Dose 2 – At least 1 ½ hours after starting Dose 1 on the evening before the colonoscopy:

1. 1. Empty the contents of 1 Pouch A and 1 Pouch B into the mixing container that comes with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
2. 2. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
3. 3. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A and B are completely dissolved.
4. 4. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all of the solution.
5. 5. Refill the mixing container to the Fill Line (32 fluid ounces) with a clear liquid and drink all this liquid before going to bed.
6. 6. Consume additional water or clear liquids up to 2 hours before the colonoscopy or as prescribed by your healthcare provider. Then stop drinking liquids until after the colonoscopy.

Stop drinking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution temporarily or drink each portion at longer intervals if severe bloating, abdominal discomfort or distention occurs, until these symptoms resolve.

3 DOSAGE FORMS AND STRENGTHS

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution is supplied as a white to yellow powder for reconstitution and is available in a carton that contains 2 pouches labeled Pouch A and 2 pouches labeled Pouch B.

• Each Pouch A contains 100 grams of polyethylene glycol (PEG) 3350, 7.5 grams of sodium sulfate, 2.691 grams of sodium chloride, and 1.015 grams of potassium chloride. Pouch A contains lemon flavoring [see Description (11)].
• Each Pouch B contains 4.7 grams of ascorbic acid and 5.9 grams of sodium ascorbate.

4 CONTRAINDICATIONS

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution is contraindicated in the following conditions:

• Gastrointestinal (GI) obstruction [see Warnings and Precautions (5.6)]
• Bowel perforation [see Warnings and Precautions (5.6)]
• Gastric retention
• Ileus
• Toxic colitis or toxic megacolon
• Hypersensitivity to any ingredient in Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution [see Warnings and Precautions (5.10) and Description (11)]

5 WARNINGS AND PRECAUTIONS

5.1 Serious Fluid and Electrolyte Abnormalities

Advise patients to hydrate adequately before, during, and after the use of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution. If a patient develops significant vomiting or signs of dehydration after taking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN).

Bowel preparations can cause fluid and electrolyte disturbances, which can lead to serious adverse reactions including cardiac arrhythmias, seizures, and renal impairment [see Adverse Reactions (6.2)]. Correct fluid and electrolyte abnormalities before treatment with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution. Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities [such as diuretics, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)] or in patients with known or suspected hyponatremia. Consider performing pre-dose and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients [see Drug Interactions (7.1)].

5.2 Cardiac Arrhythmias

There have been rare reports of serious arrhythmias (including atrial fibrillation) associated with the use of ionic osmotic laxative products for bowel preparation. These occur predominantly in patients with underlying cardiac risk factors and electrolyte disturbances. Use caution when prescribing Polyethylene Glycol-3350, Electrolytes, and Ascorbate 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, cardiomyopathy, or electrolyte imbalance). Consider pre-dose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.

5.3 Seizures

There have been rare 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, Electrolytes, and Ascorbate 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 [see Drug Interactions (7.1)].

5.4 Use in Patients with Renal Impairment

Use Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution with caution in patients with renal impairment or patients taking concomitant medications that affect renal function (such as diuretics, ACE inhibitors, angiotensin receptor blockers, or nonsteroidal anti-inflammatory drugs) [see Drug Interactions (7.1)]. These patients may be at risk for renal injury. Advise these patients of the importance of adequate hydration before, during, and after use of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, and consider performing pre-dose and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Use in Specific Populations (8.6)].

5.5 Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis

Osmotic laxatives 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, Electrolytes, and Ascorbate for Oral Solution may increase the risk of mucosal ulceration or ischemic colitis and is not recommended. Consider the potential for mucosal ulcerations resulting from the bowel preparation when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease.

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, Electrolytes, and Ascorbate for Oral Solution [see Contraindications (4)].

Use with caution in patients with severe ulcerative colitis.

5.7 Aspiration

Patients with impaired gag reflex or other swallowing abnormalities are at risk for regurgitation or aspiration of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution. Observe these patients during the administration of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution. Use with caution in these patients.

Do not combine Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution with starch-based thickeners [see Dosage and Administration (2.1)]. Polyethylene glycol (PEG), a component of Polyethylene Glycol-3350, Electrolytes, and Ascorbate 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 Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Since Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution contains sodium ascorbate and ascorbic acid, Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution should be used with caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially G6PD deficiency patients with an active infection, with a history of hemolysis, or taking concomitant medications known to precipitate hemolytic reactions.

5.9 Risks in Patients with Phenylketonuria

Phenylalanine can be harmful to patients with phenylketonuria (PKU). Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution contains phenylalanine, a component of aspartame. Each Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution treatment contains 131 mg of phenylalanine (after hydrolysis of the aspartame molecule in vivo to aspartic acid and phenylalanine). Before prescribing Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.

5.10 Hypersensitivity Reactions

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution contains polyethylene glycol (PEG) and lemon flavoring (containing citral, lime oil, maltodextrin, acacia gum, vitamin E, and other natural flavoring agents) and may cause serious hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and pruritus [see Contraindications (4), Adverse Reactions (6.2) and Description (11)]. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur.

6 ADVERSE REACTIONS

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

• Serious Fluid and Electrolyte Abnormalities [see Warnings and Precautions (5.1)]
• Cardiac Arrhythmias [see Warnings and Precautions (5.2)]
• Seizures [see Warnings and Precautions (5.3)]
• Patients with Renal Impairment [see Warnings and Precautions (5.4)]
• Colonic Mucosal Ulceration, 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)]
• Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency [see Warnings and Precautions (5.8)]
• Risks in Patients with Phenylketonuria [see Warnings and Precautions (5.9)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.10)]

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution as a Two-Day Split-Dosing and One-Day Evening Only Dosing Regimen was evaluated in two randomized, active-controlled, multicenter, investigator-blinded clinical trials in adult patients scheduled to have an elective colonoscopy [see Clinical Studies (14)]. The safety analysis for Study 1 included 359 adult patients ranging in age from 18 to 88 years (mean age 59), with 52% female and 48% male patients. The safety analysis for Study 2 included 340 adult patients ranging in age from 21 to 76 years (mean age 53), with 53% male and 47% female patients.

Tables 1 and 2 display adverse reactions reported in at least 2% and 5% of patients in either treatment group in Study 1 and Study 2, respectively. Since diarrhea was considered as a part of the efficacy assessment, it was not defined as an adverse reaction in these trials.

Table 1: Common Adverse ReactionsReported in at least 2% of patients in either treatment group in Patients Undergoing Colonoscopy in Study 1

Table 2: Common Adverse ReactionsReported in at least 5% of patients in either treatment group Patients were specifically asked about the occurrence of the following symptoms: shivering, anal irritations, abdominal bloating or fullness, sleep loss, nausea, vomiting, weakness, hunger sensation, abdominal cramps or pain, thirst sensation, and dizziness. in Patients Undergoing Colonoscopy in Study 2

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution or other PEG-based products. 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.

Cardiovascular: tachycardia, palpitations, hypertension, arrhythmia, atrial fibrillation, peripheral edema, asystole, acute pulmonary edema and syncope, and dehydration.

Gastrointestinal: upper gastrointestinal bleeding from a Mallory-Weiss tear, esophageal perforation [usually with gastroesophageal reflux disease (GERD)].

Hypersensitivity reactions: anaphylaxis (some of which were severe, including shock), rash, urticaria, pruritus, lip, tongue and facial swelling, dyspnea, chest tightness and throat tightness, rhinorrhea, dermatitis, fever, and chills [see Warnings and Precautions (5.10)].

Nervous system: tremor, seizure.

Renal: renal impairment and/or failure.

7 DRUG INTERACTIONS

7.1 Drugs That May Increase Risks due to Fluid and Electrolyte Abnormalities

Use caution when prescribing Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution for patients with conditions and/or who are using medications that increase the risk for fluid and electrolyte disturbances or may increase the risk of renal impairment, seizures, arrhythmias, or QT prolongation in the setting of fluid and electrolyte abnormalities [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)]. Consider additional patient evaluations as appropriate.

7.2 Potential for Reduced Drug Absorption

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution can reduce the absorption of other co-administered drugs. Administer oral medications at least 1 hour before the start of administration of each dose of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution [see Dosage and Administration (2.1)].

7.3 Stimulant Laxatives

Concurrent use of stimulant laxatives and Polyethylene Glycol-3350, Electrolytes, and Ascorbate 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, Electrolytes, and Ascorbate for Oral Solution [see Warnings and Precautions (5.5, 5.6)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Animal reproduction studies have not been conducted with Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation

Risk Summary

There are no data available on the presence of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution to a child during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution and any potential adverse effects on the breastfed child from Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution in pediatric patients have not been established.

8.5 Geriatric Use

Of the 413 patients in clinical trials receiving Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, 91 (22%) patients were aged 65 or older, while 25 (6%) patients were over 75 years of age. No overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between geriatric patients and younger patients. However, elderly patients are more likely to have decreased hepatic, renal or cardiac function and may be more susceptible to adverse reactions resulting from fluid and electrolyte abnormalities [see Warnings and Precautions (5.1)].

8.6 Renal Impairment

Use Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution with caution in patients with renal impairment or patients taking concomitant medications that may affect renal function [see Drug Interactions (7.1)]. These patients may be at risk for renal injury. Advise these patients of the importance of adequate hydration before, during and after the use of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Warnings and Precautions (5.4)].

10 OVERDOSAGE

Overdosage of more than the recommended dose of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution may lead to severe electrolyte disturbances, including hyponatremia and/or hypokalemia, as well as dehydration and hypovolemia, with signs and symptoms of these disturbances. Certain severe electrolyte disturbances may lead to cardiac arrhythmias, seizures, and renal failure [see Warnings and Precautions (5.1, 5.2, 5.3)]. Monitor for fluid and electrolyte disturbances and treat symptomatically.

11 DESCRIPTION

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution is an osmotic laxative consisting of 4 pouches (2 of Pouch A and 2 of Pouch B) containing white to yellow powder for reconstitution.

Each Pouch A contains 100 grams of polyethylene glycol (PEG) 3350, 7.5 grams of sodium sulfate, 2.691 grams of sodium chloride, and 1.015 grams of potassium chloride, plus the following excipients: aspartame (sweetener), acesulfame potassium (sweetener), and lemon flavoring containing citral, lime oil, maltodextrin, acacia gum, vitamin E, and other natural flavoring agents.

Pouch A contains 111.9 g of powder for oral solution.

Each Pouch B contains 4.7 grams of ascorbic acid and 5.9 grams of sodium ascorbate. Pouch B contains 10.6 g of powder for oral solution.

When 1 Pouch A and 1 Pouch B are dissolved together in water to a volume of 1 liter, Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution is an oral solution having a lemon taste.

The entire, reconstituted, 2-liter Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution colon preparation contains 200 grams of polyethylene glycol-3350, 15 grams of sodium sulfate, 5.38 grams of sodium chloride, 2.03 grams of potassium chloride, 9.4 grams of ascorbic acid, and 11.8 grams of sodium ascorbate plus the following excipients: aspartame (sweetener), acesulfame potassium (sweetener), and lemon flavoring.

A mixing container for reconstitution is enclosed.

Phenylketonurics: Contains Phenylalanine 131 mg per treatment.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The primary mode of action is osmotic action of polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid, which induce a laxative effect. The physiological consequence is increased water retention in the lumen of the colon, resulting in loose stools.

14 CLINICAL STUDIES

The colon cleansing efficacy and safety of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution was evaluated in two randomized, actively-controlled, multi-center, investigator-blinded trials in adult patients scheduled to have an elective colonoscopy.

In Study 1, patients were randomized to one of the following two colon preparation treatments: 1) 2 liters of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution with 1 additional liter of clear liquid split into two doses (during the evening before and the morning of the colonoscopy) and 2) 4 liters of polyethylene glycol plus electrolytes solution (4L PEG + E) split into two doses (during the evening before and the morning of the colonoscopy). Patients were allowed to have a morning breakfast, a light lunch, clear soup and/or plain yogurt for dinner. Dinner had to be completed at least one hour prior to initiation of the colon preparation administration.

The primary efficacy endpoint was the proportion of patients with effective colon cleansing as judged by blinded gastroenterologists on the basis of videotapes recorded during the colonoscopy.

The blinded gastroenterologists graded the colon cleansing twice (during introduction and withdrawal of the colonoscope) and the poorer of the two assessments was used in the primary efficacy analysis.

The efficacy analysis included 308 adult patients who had an elective colonoscopy. Patients ranged in age from 18 to 88 years old (mean age about 59 years old) with 52% female and 48% male patients. Table 3 displays the results.

Table 3: Effectiveness of Overall Colon Cleansing of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution vs. 4 Liter Polyethylene Glycol plus Electrolytes Solution in Study 1

4L PEG+E’s responder rate was not significantly higher than Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution’s responder rate.

In Study 2, patients were randomized to one of the following two colon preparation treatments: 1) 2 liters of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution with 1 additional liter of clear liquid in the evening prior to the colonoscopy and 2) 90 mL of oral sodium phosphate solution (90 mL OSPS) with at least 2 liters of additional clear liquid during the day and evening prior to the colonoscopy. Patients randomized to Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution therapy were allowed to have a morning breakfast; a light lunch; and clear soup and/or plain yogurt for dinner. Dinner had to be completed at least one hour prior to initiation of the colon preparation administration.

The primary efficacy endpoint was the proportion of patients with effective colon cleansing as judged by the colonoscopist and one blinded gastroenterologist (on the basis of videotapes recorded during the colonoscopy). In case of a discrepancy between the colonoscopist and the blinded gastroenterologist, a second blinded gastroenterologist made the final efficacy determination.

The efficacy analysis included 280 adult patients who had an elective colonoscopy. Patients ranged in age from 21 to 76 years old (mean age about 53 years old) with 47% female and 53% male patients. Table 4 displays the results.

Table 4: Effectiveness of Overall Colon Cleansing of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution vs. 90 mL Oral Sodium Phosphate Solution in Study 2

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution’s responder rate was not significantly higher than OSPS’s responder rate.

16 HOW SUPPLIED/STORAGE AND HANDLING

Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution (polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid for oral solution) is supplied as a white to yellow powder for reconstitution and is lemon flavored.

NDC 68682-201-75, Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, single-use outer carton:

• Each outer carton contains a disposable mixing container with lid for reconstitution of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution, prescribing information and patient information, and one inner carton.
• Each inner carton contains 2 pouches labeled Pouch A and 2 pouches labeled Pouch B.

Storage

• Store carton/container at room temperature, between 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). When reconstituted, store upright and keep solution refrigerated. Use within 24 hours [see Dosage and Administration (2.1)].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Instruct patients:

• That two doses of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution are required for a complete preparation for colonoscopy either as a Split-Dose (2-Day), or Evening Only (1-Day) dosing regimen [see Instructions for Use].
• Not to take other laxatives while they are taking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
• That Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution contains 131 mg of phenylalanine per treatment [see Warnings and Precautions (5.9)].
• That each pouch needs to be reconstituted in water before ingestion and that they should drink additional clear liquids. Examples of clear liquids can be found in the Instructions for Use.
• Not to take oral medications within one hour of starting each dose of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution.
• To follow the directions in the Instructions for Use, for either the Two-Day Split-Dosing or the One-Day Evening Only Dosing regimen, as prescribed.
• To consume additional clear liquids before, during, and after the use of Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution to prevent dehydration [see Warnings and Precautions (5.1)].
• To contact their healthcare provider if they develop significant vomiting or signs of dehydration after taking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution or if they experience altered consciousness or seizures [see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4)]
• Not to eat or drink alcohol, milk, anything colored red or purple or any other foods containing pulp material.
• To stop drinking Polyethylene Glycol-3350, Electrolytes, and Ascorbate for Oral Solution temporarily or drink each portion at longer intervals if they develop severe abdominal discomfort or distention until these symptoms diminish. If severe symptoms persist, tell patients to contact their healthcare provider.

Distributed by:

Oceanside Pharmaceuticals, a division of

Bausch Health US, LLC

Bridgewater, NJ 08807 USA

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