Sodium Sulfate, Potassium Sulfate, Magnesium Sulfate

1 INDICATIONS AND USAGE SUPREP Bowel Prep Kit is indicated for cleansing of the colon as a preparation for colonoscopy in adult and pediatric patients 12 years of age and older. SUPREP Bowel Prep Kit is an osmotic laxative indicated for cleansing of the colon in preparation for colonoscopy in adult and pediatric patients 12 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Preparation and Administration ( 2.2 ) Must dilute in water prior to ingestion. Administration of two bottles of SUPREP Bowel Prep Kit is required for a complete preparation for colonoscopy. One bottle is equivalent to one dose. Must consume additional water after each dose. Stop consumption of all fluids at least 2 hours before the colonoscopy. Recommended Dosage and Administration Split-Dose (two-day) regimen consists of two doses of SUPREP Bowel Prep Kit: first dose during the evening prior to colonoscopy and second dose the next day, during the morning of colonoscopy. ( 2.1 , 2.3 , 2.4 ) Recommended SUPREP Bowel Prep Kit dosage is: º Adults: Two 6-ounce doses. ( 2.3 ) º Pediatric Patients 12 Years of Age and Older: Two 4.5-ounce doses. ( 2.4 ) For complete information on preparation before colonoscopy and administration of the dosage regimen, see full prescribing Information. ( 2.1 , 2.2 , 2.3 , 2.4 ) 2.1 Dosage and Administration Overview Administration of two bottles of SUPREP Bowel Prep Kit and additional water is required for a complete preparation for colonoscopy. One bottle of SUPREP Bowel Prep Kit is equivalent to one dose. SUPREP Bowel Prep Kit is supplied in two dosage strengths [see Dosage Forms and Strengths ( 3 )] . The recommended dosage is: Adults: Two 6-ounce doses [see Dosage and Administration ( 2.3 )] . Pediatric patients 12 years of age and older: Two 4.5-ounce doses [see Dosage and Administration ( 2.4 )] . 2.2 Important Preparation and Administration Instructions Correct fluid and electrolyte abnormalities before treatment with SUPREP Bowel Prep Kit [see Warnings and Precautions ( 5.1 )] Must dilute SUPREP Bowel Prep Kit in water before ingestion. Must consume additional water after each dose of SUPREP Bowel Prep Kit. On the day before colonoscopy, consume only a light breakfast or clear liquids (e.g., water, strained fruit juice without pulp, lemonade, plain coffee or tea, chicken broth gelatin dessert without fruit). On the day of the colonoscopy only consume clear liquids up to two hours prior to colonoscopy. Do not eat solid food or drink milk or eat or drink anything colored red or purple. Do not drink alcohol. Do not take other laxatives while taking SUPREP Bowel Prep Kit. Do not take oral medications within one hour of starting each dose of SUPREP Bowel Prep Kit. If taking tetracycline or fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, or penicillamine, take these medications at least 2 hours before and not less than 6 hours after administration of SUPREP Bowel Kit [see Drug Interactions ( 7.2 )] . Stop consumption of all fluids at least 2 hours prior to the colonoscopy. 2.3 Recommended Dosage and Administration for Adults The recommended Split-Dose (two-day) regimen for adults consists of two 6-ounce doses of SUPREP Bowel Prep Kit: the first dose during the evening prior to colonoscopy and the second dose the next day, during the morning of the colonoscopy. Each dose consists of one bottle of SUPREP Bowel Prep Kit with additional water. The total volume of liquid required for colon cleansing (using two bottles) is 3 quarts. The following are recommended dosage and administration instructions for adults: Dose 1 – On the Day Prior to Colonoscopy: May consume a light breakfast, or only clear liquids (no solid food). In the evening before the procedure, pour the contents of one bottle of SUPREP Bowel Prep Kit into the mixing container provided. Add cool drinking water to the 16-ounce fill line on the container, mix, and drink the entire amount. Drink two additional containers filled with water to the 16-ounce fill line over the next hour. Dose 2 - Day of Colonoscopy: Continue to consume only clear liquids. In the morning (10 to 12 hours after the evening dose) on the day of the procedure, pour the contents of the second bottle of SUPREP Bowel Prep Kit into the mixing container provided. Add cool drinking water to the 16-ounce fill line on the container, mix, and drink the entire amount. Drink two additional containers filled with water to the 16-ounce fill line over the next hour. Complete all solution of SUPREP Bowel Prep Kit and required water at least two hours prior to colonoscopy. 2.4 Recommended Dosage and Administration for Pediatric Patients 12 Years of Age and Older The recommended Split-Dose (two-day) regimen for pediatric patients 12 years of age and older consists of two 4.5-ounce doses of SUPREP Bowel Prep Kit: the first dose during the evening prior to colonoscopy and the second dose the next day, during the morning of the colonoscopy. Each dose consists of one bottle of SUPREP Bowel Prep Kit with additional water. The total volume of liquid required for colon cleansing (using two bottles) is 2.25 quarts. The following are recommended dosage and administration instructions for pediatric patients 12 years of age and older and/or their caregivers: Dose 1 – On the Day Prior to Colonoscopy: May consume a light breakfast, or only clear liquids (no solid food). In the evening before the procedure, pour the contents of one bottle of SUPREP Bowel Prep Kit into the mixing container provided. Add cool drinking water to the 12-ounce fill line on the container, mix, and drink the entire amount. Drink two additional containers filled with water to the 12-ounce fill line over the next hour. Dose 2 - Day of Colonoscopy: Continue to consume only clear liquids. In the morning (10 to 12 hours after the evening dose) on the day of the procedure, pour the contents of the second bottle of SUPREP Bowel Prep Kit into the mixing container provided. Add cool drinking water to the 12-ounce fill line on the container, mix, and drink the entire amount. Drink two additional containers filled with water to the 12-ounce fill line over the next hour. Complete all solution of SUPREP Bowel Prep Kit solution and required water at least two hours prior to colonoscopy.

6 ADVERSE REACTIONS Most common adverse reactions are: Adults (>2%): overall discomfort, abdominal distention, abdominal pain, nausea, and vomiting. ( 6.1 ) Pediatric Patients (>10%): nausea, abdominal pain, abdominal bloating and vomiting. ( 6.1 ) 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 . The following important adverse reactions for bowel preparations are described elsewhere in the labeling: Serious Fluid and Serum Chemistry Abnormalities [see Warnings and Precautions ( 5.1 )] Cardiac Arrhythmias [see Warnings and Precautions ( 5.2 )] Seizures [see Warnings and Precautions ( 5.3 )] Use in Patients with Risk of Renal Injury [see Warnings and Precautions ( 5.4 )] Colonic Mucosal Ulceration 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 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 )] 6.1 Clinical Trials 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. Adults The safety of SUPREP Bowel Prep Kit was evaluated in a multi-center, randomized, active controlled trial in 379 adult patients undergoing colonoscopy [see Clinical Studies ( 14 )] . Most Common Adverse Reactions Table 1 shows the most common adverse reactions reported in at least 2% of patients receiving SUPREP Bowel Prep Kit or the control (a bowel prep containing polyethylene glycol and electrolytes (PEG + E)) administered in split-dose (2-day) regimens. Table 1: Common Adverse Reactions* in Adult Patients Undergoing Colonoscopy in a Randomized, Active Controlled Trial Symptom Split-Dose (2-Day) Regimen SUPREP Bowel Prep Kit % N=190 PEG + E product % N=189 Overall Discomfort 54 67 Abdominal Distension 40 52 Abdominal Pain 36 43 Nausea 36 33 Vomiting 8 4 * reported in at least 2% of patients Laboratory Abnormalities Table 2 shows the most common laboratory abnormalities (at least 10% in either treatment group and more than 2% difference between groups) for patients who developed new abnormalities of important electrolytes and uric acid after completing the bowel preparation with either SUPREP Bowel Prep Kit or PEG+E administered as a split-dose (2-day) regimen. Table 2: Adult Patients with Normal Baseline Serum Chemistry with A Shift to an Abnormal Value While on the Split-Dose (2-Day) Regimen 1 Day of Colonoscopy N (%) 2 Day 30 N (%) 2 Bicarbonate (low) SUPREP 20 (13) 7 (4) PEG + Electrolytes 24 (15) 4 (3) Bilirubin, total (high) SUPREP 14 (9) 0 (0) PEG + Electrolytes 20 (12) 3 (2) BUN (high) SUPREP 2 (2) 14 (11) PEG + Electrolytes 4 (3) 19 (15) Calcium (high) SUPREP 16 (10) 8 (5) PEG + Electrolytes 6 (4) 6 (4) Chloride (high) SUPREP 4 (2) 6 (4) PEG + Electrolytes 20 (12) 6 (4) Osmolality (high) SUPREP 8 (6) NA PEG + Electrolytes 19 (13) NA Uric acid (high) SUPREP 27 (24) 13 (12) PEG + Electrolytes 12 (10) 20 (17) 1 The study was not designed to support comparative claims for the laboratory abnormalities reported in this table. 2 Percent (n/N) of patients where N=number of patients with normal baseline who had abnormal values at the timepoint(s) of interest. Less Common Adverse Reactions AV Block (1 case) and CK increase. Adverse Reactions with Unapproved Use In another study of 408 adult patients, higher rates of the following adverse reactions and laboratory abnormalities were reported in patients treated with SUPREP Bowel Prep Kit as an evening-only (1-day) regimen compared to the split-dose (2-day) regimen. overall discomfort, abdominal distention, nausea, and vomiting total bilirubin (high), BUN (high), creatinine (high), osmolality (high), potassium (high) and uric acid (high) Administration of SUPREP Bowel Prep Kit in an evening-only (1-day) dosing regimen is not recommended. Pediatrics 12 Years to 16 Years of Age The safety of SUPREP Bowel Prep Kit was evaluated in a single dose-ranging clinical trial of 89 pediatric patients aged 12 years to 16 years [see Clinical Studies ( 14 )] . In 26 pediatric patients who received SUPREP Bowel Prep Kit (two 4.5-ounce doses), the most common adverse reactions (> 10%) were nausea, abdominal pain, abdominal bloating, and vomiting. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of SUPREP. 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. Hypersensitivity: anaphylaxis, angioedema, dyspnea, rash, pruritus, urticaria [see Warning and Precautions ( 5.8 )]

12.3 Pharmacokinetics Absorption and Elimination After administration of SUPREP Bowel Prep Kit in six healthy subjects, the time at which serum sulfate reached its highest point (Tmax) was approximately 17 hours after the first dose or approximately 5 hours after the second dose, and then declined with a half-life of 8.5 hours. Excretion Fecal excretion was the primary route of sulfate elimination. Specific Populations Patients with Renal Impairment The disposition of sulfate after ingestion of SUPREP Bowel Prep Kit was studied in patients (N=6) with moderate renal impairment (creatinine clearance of 30 to 49 mL/min). In patients with moderate renal impairment, mean AUC was 54% higher and mean Cmax was 44% higher, than healthy subject s. The mean sulfate concentrations in healthy subjects and in patients with moderate renal impairment returned to their respective baselines by Day 6 after dose initiation. Urinary excretion of sulfate over 30 hours after the first dose was approximately 16% lower in patients with moderate renal impairment than in healthy subjects. These differences are not considered clinically meaningful. Patients with Hepatic Impairment The disposition of sulfate after ingestion of SUPREP Bowel Prep Kit was studied in patients (N=6) with mild to moderate hepatic impairment (Child-Pugh grades A and B). Systemic exposure of serum sulfate (AUC and Cmax) was similar between healthy subjects and patients with hepatic impairment. The mean sulfate concentrations in healthy subjects and in patients with mild to moderate hepatic impairment returned to their respective baselines by Day 6 after dose initiation. Urinary excretion of sulfate over 30 hours after the first dose was similar between patients with hepatic impairment and healthy subjects.