NuLYTELY With Flavor Packs

Braintree Laboratories, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use NuLYTELY safely and effectively. See full prescribing information for NuLYTELY.NuLYTELY (polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution)Initial U.S. Approval: 1991 RECENT MAJOR CHANGESWarnings and Precautions (5) 9/2013 INDICATIONS AND USAGENuLYTELY is a combination of PEG 3350, an osmotic laxative, and electrolytes indicated for cleansing of the colon in preparation for colonoscopy in adults and pediatric patients aged 6 months or greater (1) DOSAGE AND ADMINISTRATION NuLYTELY, supplied as a powder, must be reconstituted with water before its use (2.1, 5.8) On day prior to colonoscopy, instruct patients to: Eat a light breakfast or have clear liquids (avoid red and purple liquids) (2.2). If adding a NuLYTELY flavor pack, pour the contents of flavor powder (i.e., cherry, lemon-lime, orange or pineapple) into container prior to reconstitution (2.2). Early in the evening prior to colonoscopy, fill container containing NuLYTELY powder with lukewarm water to 4 liter fill line (2.2). After capping container, shake vigorously several times (2.2). Instruct patients to consume water or clear liquids during and after bowel preparation up until 2 hours before time of colonoscopy (2.3). Adults: Drink at a rate of 240 mL (8 oz.) every 10 minutes, until 4 liters are consumed or rectal effluent is clear. For nasogastric tube (NGT), rate is 1.2 to 1.8 liters per hour (2.3) Pediatric patients (aged 6 months or greater): Drink 25 mL/kg/hour orally or administer by NGT. Continue drinking until watery stool is clear and free of solid matter (2.3). DOSAGE FORMS AND STRENGTHSFor oral solution: polyethylene glycol 3350 420 grams, sodium bicarbonate 5.72 grams, sodium chloride 11.2 grams, potassium chloride 1.48 grams, and flavoring ingredients 2 grams; supplied in one 4 liter disposable jug (3) CONTRAINDICATIONS Gastrointestinal (GI) obstruction, ileus, or gastric retention (4, 5.6) Bowel perforation (4, 5.6) Toxic colitis or toxic megacolon (4) Known allergy or hypersensitivity to components of NuLYTELY (4, 11) WARNINGS AND PRECAUTIONS Risk of fluid and electrolyte abnormalities, arrhythmias, seizures and renal impairment– assess concurrent medications and consider testing in some patients (5.1, 5.2, 5.3, 5.4) Patients with renal insufficiency– use caution, ensure adequate hydration and consider testing (5.4) Suspected GI obstruction or perforation – rule out the diagnosis before administration (4, 5.6) Patients at risk for aspiration – observe during administration (5.7) Not for direct ingestion – dilute and take with additional water (5.8) Side EffectsMost common adverse reactions (≥3%) are: nausea, abdominal fullness and bloating. Abdominal cramps, vomiting and anal irritation occur less frequently (6) To report SUSPECTED ADVERSE REACTIONS, contact Braintree Laboratories, Inc. at 1-800-874-6756 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Some drugs increase risks due to fluid and electrolyte changes (7.1) Oral medication taken within 1 hour of start of each dose may not be absorbed properly (7.2)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 NULYTELY WITH FLAVOR PACKS INDICATIONS AND USAGE
• 2 NULYTELY WITH FLAVOR PACKS DOSAGE AND ADMINISTRATION
  • 2.1 Dosage Overview
  • 2.2 Administration Instructions Prior to Dosage
  • 2.3 Dosage
• 3 DOSAGE FORMS AND STRENGTHS
• 4 NULYTELY WITH FLAVOR PACKS CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Serious Fluid and Serum Chemistry Abnormalities
  • 5.2 Cardiac Arrhythmias
  • 5.3 Seizures
  • 5.4 Renal Impairment
  • 5.5 Colonic Mucosal Ulcerations and Ischemic Colitis
  • 5.6 Use in Patients with Significant Gastrointestinal Disease
  • 5.7 Aspiration
  • 5.8 Not for Direct Ingestion
• 6 NULYTELY WITH FLAVOR PACKS ADVERSE REACTIONS
• 7 DRUG INTERACTIONS
  • 7.1 Drugs that May Lead to Fluid and Electrolyte Abnormalities
  • 7.2 Potential for Altered Drug Absorption
  • 7.3 Stimulant Laxatives
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 11 NULYTELY WITH FLAVOR PACKS DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

NuLYTELY 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

NuLYTELY, 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)]. The 4 liter reconstituted NuLYTELY solution contains: 420 grams of polyethylene glycol (PEG) 3350, 5.72 grams of sodium bicarbonate, 11.2 grams of sodium chloride, and 1.4 grams of potassium chloride. NuLYTELY may be used with or without one of the supplied flavor packs.

2.2 Administration Instructions Prior to Dosage

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

• Take only clear liquids, but avoid red and purple liquids. Patients may consume a light breakfast.
• If adding a NuLYTELY flavor pack, pour the contents of the 2 gram flavor powder (i.e., cherry, lemon-lime, orange or pineapple) into the container prior to reconstitution. No additional flavorings should be added. Discard unused flavor packs. The NuLYTELY flavor packs are for use only in combination with the contents of the accompanying 4 liter container.
• Early in the evening prior to colonoscopy, fill the supplied container containing the NuLYTELY powder (and if applicable, a flavor 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.
• 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 NuLYTELY 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 NuLYTELY 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 NuLYTELY 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

NuLYTELY 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 NuLYTELY [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 NuLYTELY. 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 NuLYTELY, 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 NuLYTELY.

In addition, use caution when prescribing NuLYTELY 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 NuLYTELY 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 NuLYTELY 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 NuLYTELY 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 postcolonoscopy 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 NuLYTELY 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 NuLYTELY. 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 NuLYTELY. 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 NuLYTELY, especially if it is administered via nasogastric tube.

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.

6 ADVERSE REACTIONS

The following adverse reactions have been identified during post-approval use of NuLYTELY. 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 NuLYTELY. 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 DRUG INTERACTIONS

7.1 Drugs that May Lead to Fluid and Electrolyte Abnormalities

Use caution when prescribing NuLYTELY 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 NuLYTELY 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 NuLYTELY may increase the risk of mucosal ulceration or ischemic colitis. Avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking NuLYTELY.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

Animal reproduction studies have not been conducted with NuLYTELY. It is also not known whether NuLYTELY can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. NuLYTELY 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 NuLYTELY is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of NuLYTELY in pediatric patients aged 6 months and older is supported by evidence from adequate and well-controlled clinical trials of NuLYTELY in adults with additional safety and efficacy data from published studies of similar formulations. Use of NuLYTELY 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 NuLYTELY 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.

11 DESCRIPTION

For oral solution: Each 4 liter (4L) NuLYTELY jug contains a white powder for reconstitution. NuLYTELY is a combination of polyethylene glycol 3350, an osmotic laxative, and electrolytes (sodium chloride, sodium bicarbonate and potassium chloride) for oral solution.

Each 4 liter jug contains: polyethylene glycol 3350 420 g, sodium bicarbonate 5.72 g, sodium chloride 11.2 g, potassium chloride 1.4 g. The solution is clear and colorless when reconstituted to a final volume of 4 liters with water.

Polyethylene Glycol 3350, NF