Potassium Sulfate

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 )

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 Prep 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 in 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 in 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.

WARNINGS AND PRECAUTIONS Risk of fluid and electrolyte abnormalities : Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after each use. ( 5.1 , 7.1 ) Cardiac arrhythmias : Consider pre-dose and post-colonoscopy ECGs in patients at increased risk. ( 5.2 ) Seizures : Use caution in patients with a history of seizures and patients at increased risk of seizures, 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 laboratory testing. ( 5.4 , 7.1 ) Suspected GI obstruction or perforation : Rule out the diagnosis before administration. ( 4 , 5.6 ) 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 ) 5.1 Serious Fluid and Serum Chemistry Abnormalities Advise all patients to hydrate adequately before, during, and after the use of SUPREP Bowel Prep Kit. If a patient develops significant vomiting or signs of dehydration after taking SUPREP Bowel Prep Kit, 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. Correct fluid and electrolyte abnormalities before treatment with SUPREP Bowel Prep Kit. Use SUPREP Bowel Prep Kit with caution in 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 )] . SUPREP Bowel Prep Kit can cause temporary elevations in uric acid [see Adverse Reactions ( 6.1 )] . Uric acid fluctuations in patients with gout may precipitate an acute flare. The potential for uric acid elevation should be considered before administering SUPREP Bowel Prep Kit to patients with gout or other disorders of uric acid metabolism. 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 SUPREP Bowel Prep Kit 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 SUPREP Bowel Prep Kit 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 Use in Patients with Risk of Renal Injury Use SUPREP Bowel Prep Kit with caution in 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 )] . These patients may be at risk for renal injury. Advise these patients of the importance of adequate hydration with SUPREP Bowel Prep Kit and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Use in Specific Populations ( 8.6 )] . 5.5 Colonic Mucosal Ulcerations and Ischemic Colitis 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 SUPREP Bowel Prep Kit may increase these risks [see Drug Interactions ( 7.3 )] . 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 SUPREP Bowel Prep Kit [see Contraindications ( 4 )] . Use with caution in patients with severe active ulcerative colitis. 5.7 Aspiration Patients with impaired gag reflex or other swallowing abnormalities are at risk for regurgitation or aspiration of SUPREP Bowel Prep Kit solution. Observe these patients during administration of SUPREP Bowel Prep Kit solution. Use with caution in these patients. 5.8 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, angioedema, dyspnea, rash, pruritus and urticaria have been reported with SUPREP [see Adverse Reactions ( 6.2 )] . Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur.

CONTRAINDICATIONS SUPREP Bowel Prep Kit is contraindicated in the following conditions: Gastrointestinal obstruction or ileus [see Warnings and Precautions ( 5.6 )] Bowel perforation [see Warnings and Precautions ( 5.6 )] Toxic colitis or toxic megacolon Gastric retention Hypersensitivity to any of the ingredients in SUPREP Bowel Prep Kit [see Warnings and Precautions ( 5.8 ) and Description ( 11 )] Gastrointestinal obstruction or ileus ( 4 , 5.6 ) Bowel perforation ( 4 , 5.6 ) Toxic colitis or toxic megacolon ( 4 ) Gastric retention ( 4 ) Hypersensitivity to any ingredient ( 4 , 5.8 )

DRUG INTERACTIONS Drugs that increase risk of fluid and electrolyte imbalance. ( 7.1 ) 7.1 Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities Use caution when prescribing SUPREP Bowel Prep Kit to patients taking medications that increase the risk of 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 [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 )]. 7.2 Potential for Reduced Drug Absorption SUPREP Bowel Prep Kit can reduce the absorption of other co-administered drugs [see Dosage and Administration ( 2.1 )] . Administer oral medications at least one hour before starting each dose of SUPREP Bowel Prep Kit. Administer tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, and penicillamine at least 2 hours before and not less than 6 hours after administration of SUPREP Bowel Prep Kit to avoid chelation with magnesium. 7.3 Stimulant Laxatives Concurrent use of stimulant laxatives and SUPREP Bowel Prep Kit may increase the risk of mucosal ulceration or ischemic colitis. Avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking SUPREP Bowel Prep Kit [see Warnings and Precautions ( 5.5 )] .

ADVERSE REACTIONS Most common adverse reactions (≥3%) are: overall discomfort, abdominal fullness, nausea, abdominal cramping, and vomiting ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novel Laboratories, Inc. at 866-403-7592 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 multicenter, controlled clinical trial comparing Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution with a bowel prep containing polyethylene glycol and electrolytes (PEG + E) that were administered in a split-dose (2-day) regimen, the most common adverse reactions after administration of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution were overall discomfort, abdominal distention, abdominal pain, nausea, vomiting, and headache; see Table 1, below. Less common Adverse Reactions occurring were AV Block (1 case) and CK increase. In this study, patients receiving Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution were limited to a light breakfast followed by clear liquids; patients receiving the PEG + E bowel prep were allowed to have a normal breakfast and a light lunch, followed by clear liquids. Table 1: Treatment-Emergent Adverse Reactions Observed in at Least 2% of Patients on the Split-Dose (2-Day) Regimen Symptom Split-Dose (2-Day) Regimen Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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% Headache 1.1% 0.5% Table 2 shows the percentages of patients who developed new abnormalities of important electrolytes and uric acid after completing the bowel preparation with either Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution or PEG+E administered as a split-dose (2-day) regimen. Table 2: Patients with Normal Baseline Serum Chemistry with A Shift to an Abnormal Value While on the Split-Dose (2-Day) Regimen Day of Colonoscopy n (%)* Day 30n (%)* Anion gap (high) † Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 14 (8.9) 3 (1.9) PEG + Electrolytes 12 (7.6) 2 (1.4) Bicarbonate (low) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 20 (12.7) 7 (4.4) PEG + Electrolytes 24 (15.2) 4 (2.7) Bilirubin, total (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 14 (8.5) 0 (0) PEG + Electrolytes 20 (11.7) 3 (1.9) BUN (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 2 (1.6) 14 (11.2) PEG + Electrolytes 4 (2.9) 19 (14.5) Calcium (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 16 (10.4) 8 (5.2) PEG + Electrolytes 6 (3.7) 6 (3.9) Chloride (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 4 (2.4) 6 (3.7) PEG + Electrolytes 20 (12.2) 6 (3.8) Creatinine (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 3 (1.9) 5 (3.2) PEG + Electrolytes 2 (1.2) 8 (5.2) Osmolality (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 8 (5.8) NA PEG + Electrolytes 19 (12.9) NA Osmolality (low) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 3 (2.2) NA PEG + Electrolytes 2 (1.4) NA Potassium (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 3 (1.8) 6 (3.7) PEG + Electrolytes 5 (2.9) 8 (4.9) Sodium (low) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 5 (3.1) 1 (0.6) PEG + Electrolytes 4 (2.3) 2 (1.2) Uric acid (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 27 (23.5) 13 (11.5) PEG + Electrolytes 12 (9.5) 20 (16.7) There were also 408 patients who participated in a study in which either Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution or PEG+E were administered in an evening-only (1-day) regimen. Higher rates of overall discomfort, abdominal distention, and nausea were observed with the evening-only (1-day) regimen compared to the split-dose (2-day) regimen for both preparations. Patients treated with Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution had increased rates of vomiting with the evening-only (1-day) regimen. An evening-only (1-day) dosing regimen was associated with higher rates of abnormal values for some electrolytes when compared to the split-dose (2-day) regimen for both preparations. For Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution, the evening-only (1-day) regimen was associated with higher rates of total bilirubin (high), BUN (high), creatinine (high), osmolality (high), potassium (high) and uric acid (high) than the Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution split dose (2-day) regimen. Administration of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution in an evening-only (1-day) dosing regimen is not recommended.

Mechanism of Action Sulfate salts provide sulfate anions, which are poorly absorbed. The osmotic effect of unabsorbed sulfate anions and the associated cations causes water to be retained within the gastrointestinal tract.