SODIUM SULFATE, POTASSIUM SULFATE AND MAGNESIUM SULFATE

1 INDICATIONS AND USAGE Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution is indicated for cleansing of the colon as a preparation for colonoscopy in adult and pediatric patients 12 years of age and older. Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution: 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution dosage is: Adults: Two 6-ounce doses. ( 2.3 ) 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution and additional water is required for a complete preparation for colonoscopy. One bottle of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution is equivalent to one dose. Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution [see Warnings and Precautions ( 5.1 )] Must dilute Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution in water before ingestion. Must consume additional water after each dose of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. Do not take oral medications within one hour of starting each dose of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution [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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution: 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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…

5 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. If a patient develops significant vomiting or signs of dehydration after taking Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution, 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. Use Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 )] . Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate 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 Use in Patients with Risk of Renal Injury Use Sodium Sulfate, Potassium Sulfate and Magnesium…

4 CONTRAINDICATIONS Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution [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)

7 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. Administer tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, and penicillamine at least 2 hours before and not less than 6 hours after administration of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution to avoid chelation with magnesium. 7.3 Stimulant Laxatives Concurrent use of stimulant laxatives and Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution may increase the risk of mucosal ulceration or ischemic colitis. Avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution [see Warnings and Precautions ( 5.5 )] .

8.1 Pregnancy Risk Summary There are no available data on Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproductive studies have not been conducted with sodium sulfate, potassium sulfate, and magnesium sulfate. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

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 Wilshire Pharmaceuticals, Inc. at 1-800-461-7449 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 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 * 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 20 (13) 7 (4) PEG + Electrolytes 24 (15) 4 (3) Bilirubin, total (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 14 (9) 0 (0) PEG + Electrolytes 20 (12) 3 (2) BUN (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 2 (2) 14 (11) PEG + Electrolytes 4 (3) 19 (15) Calcium (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 16 (10) 8 (5) PEG + Electrolytes 6 (4) 6 (4) Chloride (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 4 (2) 6 (4) PEG + Electrolytes 20 (12) 6 (4) Osmolality (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 8 (6) NA PEG + Electrolytes 19 (13) NA Uric acid (high) Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 wher…