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PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate and Ascorbic Acid for Oral Solution

TABLE OF CONTENTS

1. DESCRIPTION 7. WARNINGS AND PRECAUTIONS
2. INDICATIONS AND USAGE 8. ADVERSE REACTIONS
3. DOSAGE AND ADMINISTRATION 9. OVERDOSAGE
4. CONTRAINDICATIONS 10. DRUG INTERACTIONS
5. MECHANISM OF ACTION 11. PHARMACOKINETICS
6. USE IN SPECIFIC POPULATIONS 12. HOW SUPPLIED/STORAGE AND HANDLING


1. DESCRIPTION

PEG-3350 Cleansing Solution consists of 4 separate 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, NF, 7.5 grams of sodium sulfate, USP, 2.691 grams of sodium chloride, USP, and 1.015 grams of potassium chloride, USP, plus the following excipients: aspartame, NF (sweetener), acesulfame potassium, NF (sweetener), and lemon flavoring. Each pouch B contains 4.7 grams of ascorbic acid, USP and 5.9 grams of sodium ascorbate, USP. When 1 pouch A and 1 pouch B are dissolved together in water to a volume of 1 liter, PEG-3350 Cleansing Solution is an oral solution having a lemon taste.

The entire, reconstituted, 2-liter PEG-3350 Cleansing Solution colon preparation contains 200 grams of PEG 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.

2. INDICATIONS AND USAGE

PEG-3350 Cleansing Solution is indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older.

3. DOSAGE AND ADMINISTRATION

The PEG-3350 Cleansing Solution dose for colon cleansing for adult patients is 2 liters (approximately 64 ounces) of PEG-3350 Cleansing Solution (with 1 additional liter of clear fluids) taken orally prior to the colonoscopy in one of the following ways:

1) Split-dose PEG-3350 Cleansing Solution regimen: The evening before the colonoscopy, take the first liter of PEG-3350 Cleansing Solution over one hour (one 8 ounce glass every 15 minutes) and then drink 0.5 liters (approximately 16 ounces) of clear fluid. Then, on the morning of the colonoscopy, take the second liter of PEG-3350 Cleansing Solution over one hour and then drink 0.5 liters of clear liquid at least one hour prior to the start of the colonoscopy; or

2) Evening-only (Full-dose) PEG-3350 Cleansing Solution regimen: Around 6 PM in the evening before the colonoscopy, take the first liter of PEG-3350 Cleansing Solution over one hour (one 8 ounce glass every 15 minutes) and then about 1.5 hours later take the second liter of PEG-3350 Cleansing Solution over one hour. In addition, take 1 liter (approximately 32 ounces) of additional clear liquid during the evening before the colonoscopy.

Preparation of the PEG-3350 Cleansing Solution:

PEG-3350 Cleansing Solution is prepared by emptying the contents of 1 pouch A and 1 pouch B into a suitable glass container (or the container provided) and adding to the container 1 liter of lukewarm water. Mix the solution to ensure that the ingredients are completely dissolved. If the patient prefers, the PEG-3350 Cleansing Solution can be refrigerated prior to drinking. The reconstituted solution should be used within 24 hours.

No additional ingredients (e.g., flavorings) should be added to the PEG-3350 Cleansing Solution.

After consumption of the first liter of PEG-3350 Cleansing Solution, the above mixing procedure should be repeated with the second pouch A and pouch B to reconstitute the second liter of the PEG-3350 Cleansing Solution.

4. CONTRAINDICATIONS

PEG-3350 Cleansing Solution is contraindicated in the following conditions:

• Gastrointestinal (GI) obstruction

• Bowel perforation

• Gastric retention

• Ileus

• Toxic colitis or toxic megacolon

• Hypersensitivity to any components of PEG-3350 Cleansing Solution [see Description]

5. MECHANISM OF ACTION

PEG-3350 Cleansing Solution produces a watery stool leading to cleansing of the colon. The osmotic activity of polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid, when taken with 1 liter of additional clear fluid, usually results in no net absorption or excretion of ions or water.

6. USE IN SPECIFIC POPULATIONS

6.1 Usage in Pregnancy

Pregnancy Category C

Animal reproduction studies have not been performed with PEG-3350 Cleansing Solution. It is also not known if PEG-3350 Cleansing Solution can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. PEG-3350 Cleansing Solution should be given to a pregnant woman only if clearly needed.

6.2 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 PEG-3350 Cleansing Solution is administered to a nursing woman.

6.3 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

6.4 Geriatric Use

Of the 413 patients in clinical studies receiving PEG-3350 Cleansing 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, but greater sensitivity of some older individuals cannot be ruled out.

7. WARNINGS AND PRECAUTIONS

7.1 Serious Fluid and Electrolyte Abnormalities

Advise patients to hydrate adequately before, during, and after the use of PEG-3350 Cleansing Solution. If a patient develops significant vomiting or signs of dehydration after taking PEG-3350 Cleansing Solution consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN). Fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias, seizures and renal impairment.

Patients with electrolyte abnormalities should have them corrected before treatment with PEG-3350 Cleansing Solution. PEG-3350 Cleansing 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 postcolonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients. [See Drug Interactions].

7.2 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 Cleansing 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.

7.3 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 PEG-3350 Cleansing 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.

7.4 Renal Impairment

Use with caution in patients with impaired renal function or patients taking concomitant medications that affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or nonsteroidal anti-inflammatory drugs). Advise these patients of the importance of adequate hydration, and consider performing pre-dose and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.

7.5 (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 PEG-3350 Cleansing Solution may increase the risk and is not recommended. The potential for mucosal ulcerations resulting from the bowel preparation should be considered when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease.

7.6 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 Cleansing Solution. If a patient experiences severe bloating, abdominal distension, or abdominal pain, administration should be slowed or temporarily discontinued until symptoms abate.

Use with caution in patients with severe ulcerative colitis.

7.7 Aspiration

Patients with impaired gag reflex and patients prone to regurgitation or aspiration should be observed during the administration of PEG-3350 Cleansing Solution. Use with caution in these patients.

7.8 Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency

Since PEG-3350 Cleansing Solution contains sodium ascorbate and ascorbic acid, PEG-3350 Cleansing Solution should be used with caution in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, especially G-6-PD deficiency patients with an active infection, with a history of hemolysis, or taking concomitant medications known to precipitate hemolytic reactions.

7.9 Contains Phenylalanine

Phenylketonurics: Contains aspartame 233 mg per treatment which corresponds to 131 mg of phenylalanine per treatment (after hydrolysis of the aspartame molecule in-vivo to aspartic acid and phenylalanine).

8. ADVERSE REACTIONS

8.1 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.

In the PEG-3350 Cleansing Solution trials, abdominal distension, anal discomfort, thirst, nausea, and abdominal pain were some of the most common adverse reactions to PEG-3350 Cleansing Solution administration. Since diarrhea was considered as a part of the efficacy of PEG-3350 Cleansing Solution, diarrhea was not defined as an adverse reaction in the clinical studies. Tables 1 and 2 display the most common drug-related adverse reactions of PEG-3350 Cleansing Solution and its comparator in the controlled PEG-3350 Cleansing Solution trials.

Table 1: The Most Common Drug-Related Adverse Reactions1 (≥ 2%) in the Study of PEG-3350 Cleansing Solution vs. 4 liter Polyethylene Glycol plus Electrolytes Solution

1 Drug-related adverse reactions were adverse events that were possibly, probably, or definitely related to the study drug.

2 4L PEG + E is 4 liter Polyethylene Glycol plus Electrolytes Solution

Table 2: The Most Common Drug-Related Adverse Reactions1 (≥ 5%) in the Study of PEG-3350 Cleansing Solution vs. 90 mL Oral Sodium Phosphate Solution

1 Drug-related adverse reactions were adverse events that were possibly, probably, or definitely related to the study drug. In addition to the recording of spontaneous adverse events, patients were also 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.

2 OSPS is Oral Sodium Phosphate Solution

Published literature contains isolated reports of serious adverse events following the administration of PEG-based products in patients over 60 years of age. These adverse events included upper gastrointestinal bleeding from a Mallory-Weiss tear, esophageal perforation, asystole, and acute pulmonary edema after aspirating the PEG-based preparation.

8.2 Postmarketing Experience

In addition to adverse events reported from clinical trials, the following adverse events have been identified during post-approval use of PEG-3350 Cleansing Solution. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to PEG-3350 Cleansing Solution, or a combination of these factors.

General: Hypersensitivity reactions including anaphylaxis (some of which were severe, including shock), rash, urticaria, pruritus, lip, tongue and facial swelling, dyspnea, chest tightness and throat tightness. Fever, chills and dehydration.

9. OVERDOSAGE

There have been no reported cases of overdose with PEG-3350 Cleansing Solution. Purposeful or gross accidental ingestion of more than the recommended dose of PEG-3350 Cleansing Solution might be expected to lead to severe electrolyte disturbances, including hyponatremia and/or hypokalemia, as well as dehydration and hypovolemia, with signs and symptoms of these disturbances. The patient who has taken an overdose should be monitored carefully, and treated symptomatically for complications until stable.

10. DRUG INTERACTIONS

10.1 Drugs That May Increase Risks Due to Fluid and Electrolyte Abnormalities

Use caution when prescribing PEG-3350 Cleansing Solution for patients with conditions, or who are using mediations 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].

10.2 Potential for Altered Drug Absorption

Oral medication administered within 1 hour of the start of administration of PEG-3350 Cleansing Solution may be flushed from the gastrointestinal tract and the medication may not be absorbed.

11. PHARMACOKINETICS

No pharmakokinetic information is available.

12. HOW SUPPLIED/STORAGE AND HANDLING

1) How Available:

a) Brand name: MOVIPREP, by SALIX PHARMS.

b) Generic drugs: ASCORBIC ACID; POLYETHYLENE GLYCOL 3350; POTASSIUM CHLORIDE; SODIUM ASCORBATE; SODIUM CHLORIDE; SODIUM SULFATE, by Novel Labs.

2) How Supplied:

MoviPrep® is supplied as a white to yellow powder. MoviPrep is administered as an oral solution after reconstitution.

NDC 65649-201-75, MoviPrep, single use carton.

NDC 65649-201-76, MoviPrep, professional sample carton.

Each carton contains a disposable container for reconstitution of MoviPrep and an inner carton containing 4 pouches (2 of pouch A and 2 of pouch B).

3) Storage and Handling:

Store carton/container at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). When reconstituted, store upright and keep solution refrigerated. Use within 24 hours.

Rx only

Rev 08/12