GaviLyte-H and Bisacodyl

1 INDICATIONS & USAGE GaviLyte - H and bisacodyl delayed-release tablet, USP is indicated for cleansing of the colon as a preparation for colonoscopy in adults. GaviLyte - H and bisacodyl delayed-release tablet, USP is a combination of PEG-3350, an osmotic laxative and bisacodyl, a stimulant laxative, indicated for cleansing of the colon as a preparation for colonoscopy in adults ( 1 )

2 DOSAGE & ADMINISTRATION The recommended GaviLyte - H and bisacodyl delayed-release tablet, USP oral dosage regimen for adults on the day prior to colonoscopy is as follows: No solid food or milk (clear liquids only) should be consumed on the day of the preparation. Take one 5 mg bisacodyl delayed-release tablet, USP with water. Do NOT chew or crush the tablet. No antacids should be taken within one hour of taking the bisacodyl delayed-release tablet, USP. Prepare the GaviLyte - H solution according to the instructions on the kit. Add flavor pack of choice (if applicable) to the 2 liter container. No additional ingredients (other than flavor packs provided) should be added to the solution. Prepare the GaviLyte - H solution by filling the container to the 2 liter mark with water. Cap the container. Shake to dissolve the powder. Wait for a bowel movement (or maximum of 6 hours) then drink the 2 liter GaviLyte - H solution at a rate of 8 ounces every 10 minutes. Drink all of the solution. If you have abdominal distention or discomfort, stop drinking the GaviLyte - H solution temporarily or drink each portion at longer intervals until your symptoms improve. Consume only clear liquids after taking the GaviLyte - H solution until your colonoscopy. See FULL PRESCRIBING INFORMATION for complete dosing and administration instructions ( 2 ) No solid food or milk (clear liquids only) should be consumed on the day of the preparation. Take one 5 mg bisacodyl tablet with water. Do NOT chew or crush. Dissolve the GaviLyte - H powder in 2 liters of water. Wait for a bowel movement (or maximum of 6 hours) then drink all the GaviLyte - H solution at a rate of 8 ounces every 10 minutes. Consume only clear liquids until the colonoscopy.

4 CONTRAINDICATIONS The GaviLyte - H and bisacodyl delayed-release tablet, USP is contraindicated in the following conditions: Gastrointestinal (GI) obstruction Bowel perforation Toxic colitis and toxic megacolon Gastric retention Ileus Gastrointestinal (GI) obstruction ( 4 ) Bowel perforation ( 4 ) Toxic colitis or toxic megacolon ( 4 ) Gastric retention ( 4 ) Ileus ( 4 )

5 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 impairment – use caution, ensure adequate hydration and consider testing ( 5.3 ) Ischemic colitis has been reported ( 5.5 ) Suspected GI obstruction or perforation – rule out the diagnosis before administration ( 5.6 ) Patients at risk for aspiration – observe during administration ( 5.7 ) 5.1 Serious Fluid and Serum Chemistry Abnormalities Advise all patients to hydrate adequately before, during, and after the use of GaviLyte - H and bisacodyl delayed-release tablet, USP. If a patient develops significant vomiting or signs of dehydration after taking GaviLyte - H and bisacodyl delayed-release tablet, USP, 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 GaviLyte - H and bisacodyl delayed-release tablet, USP. In addition, use caution when prescribing GaviLyte - H and bisacodyl delayed-release tablet, USP for patients with 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 Seizures There have been reports of generalized tonic-clonic seizures with the use of large volume (4 liter) PEG-based colon 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 the GaviLyte - H and bisacodyl delayed-release tablet, USP for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, patients with known or suspected hyponatremia, or patients using concomitant medications (such as diuretics) that increase the risk of electrolyte abnormalities. Monitor baseline and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients. 5.3 Renal Impairment Patients with impaired water handling who experience severe vomiting should be closely monitored including measurement of electrolytes (sodium, potassium, calcium, BUN and creatinine). Use caution when prescribing GaviLyte - H and bisacodyl delayed-release tablet, USP 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. 5.4 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 GaviLyte - H and bisacodyl delayed-release tablet, USP 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. 5.5 Ischemic Colitis There have been reports of ischemic colitis in patients with use of GaviLyte - H and 20 mg bisacodyl delayed-release tablet, USP and GaviLyte - H and 10 mg bisacodyl delayed-release tablet, USP. If patients develop severe abdominal pain or rectal bleeding, patients should be evaluated as soon as possible. 5.6 Patients with Significant Gastrointestinal Disease If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering GaviLyte - H and bisacodyl delayed-release tablet, USP Use with caution in patients with severe active ulcerative colitis. 5.7 Aspiration Use with caution in patients with impaired gag reflex and patients prone to regurgitation or aspiration. Such patients should be observed during administration of the GaviLyte - H and bisacodyl delayed-release tablet, USP solution.

7 DRUG INTERACTIONS Some drugs (e.g., diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) increase risk due to fluid and electrolyte changes ( 7.1 ) Oral medication administered within one hour of the start of drinking GaviLyte - H might not be absorbed fully. ( 7.2 ) Do not take the bisacodyl tablet within one hour of taking antacid ( 7.3 ) 7.1 Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities Use caution when prescribing GaviLyte - H and bisacodyl delayed-release tablet, USP for patients with 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 prolonged QT in the setting of fluid and electrolyte abnormalities. Consider additional patient evaluations as appropriate [see Warnings and Precautions ( 5.1 )] 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 GaviLyte - H solution may be flushed from the GI tract and the medication may not be absorbed completely. 7.3 Interaction with Antacids Do not take the bisacodyl delayed-release tablet within one hour of taking an antacid.

6 ADVERSE REACTIONS Most common adverse reactions (>3%) are overall discomfort, abdominal fullness, abdominal cramping, nausea, and vomiting, ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novel Laboratories, Inc. at 908-603-6000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in clinical studies of another drug and may not reflect the rates observed in practice. In a clinical study of GaviLyte - H and (5 mg vs. 10 mg) bisacodyl delayed-release tablet, USP, overall discomfort, abdominal fullness, abdominal cramping, nausea, and vomiting, were the most common adverse reactions (>3%). The data in Table 1 reflects the 154 patients that received GaviLyte - H and 5 mg bisacodyl tablet vs. the 154 patients that received GaviLyte - H and 10 mg bisacodyl tablets. The GaviLyte - H and 5 mg bisacodyl delayed-release tablet, USP population was 29-87 years of age, 49% male, 51% female, 13% African American, 83% White, 5% Hispanic requiring a colonoscopy. The demographics of the comparator group were similar. Table 1: Adverse Reactions Observed in at Least 3% of Randomized Patients GaviLyte - H and 5 mg Bisacodyl Delayed-release Tablet, USP(N=154)] GaviLyte - H and 10 mg Bisacodyl Delayed-release Tablet, USP(N=154) Overall Discomfort 57% 66% Abdominal fullness 40% 53% Abdominal cramping 38% 46% Nausea 34% 42% Vomiting 10% 7% 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of GaviLyte - H and bisacodyl delayed-release tablet, USP. 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. Allergic Reactions: Cases of urticaria, rhinorrhea, dermatitis and anaphylactic reactions have been reported with PEG-based products. Gastrointestinal: There are isolated reports of serious post-marketing events following the administration of PEG-based products in patients over 60 years of age. These adverse reactions include upper GI bleeding from a Mallory-Weiss tear, esophageal perforation, asystole, and acute pulmonary edema after vomiting and aspirating the PEG-based solution. In addition, during administration of 4 liters of PEG-3350 colon cleansing preparation the following serious adverse reactions were seen: two deaths in end stage renal failure patients who developed diarrhea, vomiting and dysnatremia [ see Warnings and Precautions ( 5.3 ) ]. Ischemic colitis has been reported with use of of GaviLyte - H and 20 mg and 10 mg bisacodyl delayed-release tablets, USP for colon preparation prior to colonoscopy. However, a causal relationship between these ischemic colitis cases and the use of GaviLyte - H and bisacodyl delayed-release tablets, USP has not been established. Neurologic: There have been reports of generalized tonic-clonic seizures associated with use of large volume (4 liter) PEG-based colon preparation products in patients with no prior history of seizures. Cases of dizziness and syncope have been reported [see Warnings and Precautions ( 5.1 )] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C animal reproduction studies have not been conducted. It is not known whether GaviLyte - H and bisacodyl delayed-release tablet, USP can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. GaviLyte - H and bisacodyl delayed-release tablet, USP should be given to a pregnant or nursing 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 GaviLyte - H and bisacodyl delayed-release tablet, USP is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness in pediatric patients has not been established. 8.5 Geriatric Use Of the 148 patients who took GaviLyte - H and 5 mg bisacodyl delayed-release tablet, USP in clinical trials, 42 (28%) were 65 years of age or older, while 10 (7%) were 75 years of age or older. The rates of success appear to be lower in patients 65 years and older [see Clinical Studies ( 14 )] .