Polyethylene Glycol-3350 and Electrolytes

Preparation and Administration (2.1): Correct fluid and electrolyte abnormalities before treatment with PEG-3350 and electrolytes for oral solution. Reconstitute PEG-3350 and electrolytes for oral solution with water prior to ingestion. Do not take oral medications within 1 hour before the start or during administration of PEG-3350 and electrolytes for oral solution. (2.1) Do not take other laxatives while taking PEG-3350 and electrolytes for oral solution. Consume only clear liquids; avoid red and purple liquids. Consume water or other clear liquids up until 2 hours before the time of the colonoscopy. Do not consume solid food within 2 hours before starting PEG-3350 and electrolytes for oral solution. Adult Dosing Regimen (2.2): On day prior to colonoscopy, instruct patients to consume a light breakfast at least 2 hours before starting PEG-3350 and electrolytes for oral solution. Begin the recommended dosage regimen for PEG-3350 and electrolytes for oral solution early in the evening on the day before colonoscopy Drink reconstituted solution at a rate of 8 ounces every 10 minutes, until 4 liters are consumed, or rectal effluent is clear. For complete information on dosing, preparation and administration, see the full prescribing information. (2.1, 2.2)

2.1Important Preparation and Administration Instructions

Correct fluid and electrolyte abnormalities before treatment with PEG-3350 and electrolytes for oral solution [see Warnings and Precautions (5.1)]. Reconstitute PEG-3350 and electrolytes for oral solutionwith water prior to ingestion, do not take undissolved PEG-3350 and electrolytes for oral solution [see Dosage and Administration (2.2)]. Do not take oral medications within 1 hour before the start of or during administration of PEG-3350 and electrolytes for oral solution [see Drug Interactions (7.2)]. Do not take other laxatives while taking PEG-3350 and electrolytes for oral solution [see Drug Interactions (7.3)]. Consume only clear liquids, avoid red and purple liquids. Patients may consume water or other 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. Do not consume solid food within 2 hours before starting PEG-3350 and electrolytes for oral solution. For the best results, do not consume solid food for 3 to 4 hours before drinking the solution. If severe bloating, distention or abdominal pain occurs, slow or temporarily discontinue PEG-3350 and electrolytes for oral solution until the symptoms abate. 2.2 Dosage Regimen Instruct adult patients that on the day before the colonoscopy procedure, they may consume a light breakfast at least 2 hours before starting PEG-3350 and electrolytes for oral solution. Begin the recommended dosage regiment for PEG-3350 and electrolytes for oral solution early in the evening on the day before colonoscopy. Instruct patients to take PEG-3350 and electrolytes for oral solution in conjunction with clear liquids as follows: This preparation can be used with or without the lemon flavor pack. The pharmacist will add the lemon flavor pack prior to dispensing (see packet instructions) 4 Liter Jug Fill the supplied container containing the PEG-3350 and electrolytes for oral solution powder with lukewarm drinking water to the 4-liter fill line Do not add any other ingredients, flavors, etc After capping the container, shake vigorously several times to ensure that the ingredients are dissolved. Drink at a rate of 8 ounces every 10 minutes until the entire contents are consumed or the rectal effluent is clear. A loose watery bowel movement should result in approximately one hour. After reconstitution, keep solution refrigerated 2° to 8°C (36° to 46°F). Do not freeze. Use within 48 hours, discard unused portion. Administration via a Nasogastric Tube For patients with a nasogastric tube, administer the reconstituted PEG-3350 and electrolytes for oral solution solution at a rate of 20 to 30 mL per minute (1.2 to 1.8 liters per hour).

Risk of fluid and electrolyte abnormalities: Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use. (5.1, 5.2, 7.1) Cardiac arrhythmias: Consider pre-dose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. (5.2) Seizures: Use caution in patients with a history of seizures and patients at increased risk of seizure, including medications that lower the seizure threshold. (5.3, 7.1) Patients with renal impairment or taking concomitant medications that affect renal function: Use caution, ensure adequate hydration and consider testing. (5.4, 7.1, 8.6) Mucosal ulcerations: Consider potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. (5.5, 7.3) Patients at risk for aspiration: Observe during administration. (5.7) Hypersensitivity reactions including anaphylaxis: Inform patients to seek immediate medical care if symptoms occur. (5.8)

5.1Serious Fluid and Serum Chemistry Abnormalities

Advise patients to hydrate adequately before, during, and after the use of PEG-3350 and electrolytes 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 and electrolytes for oral solution, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Correct fluid and electrolyte abnormalities before treatment with PEG-3350 and electrolytes for oral solution. 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 and electrolytes for oral solution. In addition, use caution when prescribing PEG-3350 and electrolytes 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)]

5.2Cardiac 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 and electrolytes 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). Consider pre-dose and post-colonoscopy ECGs 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 and electrolytes 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 Renal Impairment Use caution when prescribing PEG-3350 and electrolytes 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) [see Drug Interactions (7.1)]. 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 [see Use is Specific Populations (8.6)]

5.5Colonic 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 and electrolytes for oral solution may increase this risk. Consider the potential for mucosal ulcerations resulting from the bowel preparation 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 and electrolytes 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 and electrolytes 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. Observe these patients during administration of PEG-3350 and electrolytes for oral solution, especially if it is administered via nasogastric tube." Do not combine PEG-3350 and electrolytes for oral solution with starch-based thickeners [see Dosage and Administration (2.1)]. Polyethylene glycol (PEG), a component of PEG-3350 and electrolytes 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 chocking and potential aspiration were reported. 5.8 Hypersensitivity Reactions PEG-3350 and electrolytes for oral solution contains PEG and may cause serious hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and pruritus [see Adverse Reactions (6)]. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur.

Most common adverse reactions (≥3%) are: nausea, abdominal fullness and bloating abdominal cramps, vomiting and anal irritation (6) To report SUSPECTED ADVERSE REACTIONS, contact Novel Laboratories, Inc. at 1-866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following clinically significant adverse reactions are described elsewhere in the labeling: Renal impairment [see Warnings and Precautions (5.4)] Colonic mucosal ulcerations and ischemic 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)] The following adverse reactions associated with the use of PEG-3350 and electrolytes for oral solution were identified in clinical trials or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or establish a causal relationship to drug exposure. Cardiovascular: arrhythmia, atrial fibrillation, peripheral edema, asystole, and acute pulmonary edema after aspiration [see Warnings and Precautions (5.2)]. Nervous system: tremor, seizure [see Warnings and Precautions (5.3)] Hypersensitivity: Urticaria/rash, pruritus, dermatitis, rhinorrhea, dyspnea, chest and throat tightness, fever, angioedema, anaphylaxis and anaphylactic shock [see Contraindications (4), Warnings and Precautions (5.8)] Gastrointestinal: Nausea, abdominal fullness and bloating are the most common adverse reactions (occurred in up to 50% of patients). Other less common adverse reactions include: abdominal cramps, vomiting, "butterfly-like" infiltrates on chest X-ray after vomiting and aspirating PEG, anal irritation, and upper GI bleeding from Mallory-Weiss Tear, esophageal perforation [usually with gastroesophageal reflux disease (GERD)].

8.1Pregnancy

Animal reproduction studies have not been conducted with PEG-3350 and electrolytes for oral solution. It is also not known whether PEG-3350 and electrolytes for oral solution can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. PEG-3350 and electrolytes 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 PEG-3350 and electrolytes for oral solution is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness of PEG-3350 and electrolytes for oral solution in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of PEG-3350 and electrolytes 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. 8.6 Renal Impairment Use PEG-3350 and electrolytes 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 use of PEG-3350 and electrolytes 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)].