DESCRIPTION SECTION

11 DESCRIPTION

Sodium sulfate, potassium sulfate, and magnesium sulfate oral solution**(for adults)**is an osmotic laxative and is provided as two bottles each containing 6 ounces of solution.

Each bottle contains: 17.5 grams sodium sulfate, 3.13 grams potassium sulfate, and 1.6 grams magnesium sulfate. Inactive ingredients include: art cherry flavor, citric acid, dibasic sodium phosphate anhydrous, malic acid, monobasic sodium phosphate anhydrous, purified water, sodium benzoate, sucralose.

Sodium Sulfate, USP

The chemical name is Na2SO4. The average Molecular Weight is 142.04. The structural formula is:


Potassium Sulfate, FCC, purified

The chemical name is K2SO4. The average Molecular Weight is 174.26. The structural formula is:


Magnesium Sulfate, USP

The chemical name is MgSO4. The average Molecular Weight: 120.37. The structural formula is:


Each sodium sulfate, potassium sulfate, and magnesium sulfate oral solution also contains a polypropylene mixing container.

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

CLINICAL PHARMACOLOGY SECTION

12 CLINICAL PHARMACOLOGY

12.1 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.

12.2 Pharmacodynamics

No formal pharmacodynamic studies have been conducted with sodium sulfate, potassium sulfate and magnesium sulfate oral solution.

12.3 Pharmacokinetics

Absorption and Elimination

After administration of sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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 subjects.

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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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.

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INDICATIONS & USAGE SECTION

1 INDICATIONS & USAGE

Sodium sulfate, potassium sulfate and magnesium sulfate oral solution is indicated for cleansing of the colon as a preparation for colonoscopy in adult patients.

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

DOSAGE & ADMINISTRATION SECTION

Highlight: 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)
• Recommended sodium sulfate, potassium sulfate and magnesium sulfate oral solution dosage is: o**Adults:**Two 6-ounce doses. (2.3)
• For complete information on preparation before colonoscopy and administration of the dosage regimen, see full prescribing Information. (2.1, 2.2, 2.3)

2 DOSAGE AND ADMINISTRATION

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 one dosage strength [see Dosage Forms and Strengths (3)]. The recommended dosage is:

***Adults:**Two 6-ounce doses [see Dosage and Administration (2.3)].

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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 in Adults

The recommended Split-Dose (two-day) regimen foradultsconsists 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 (no solid food).
• In the evening before the procedure, pour the contents of one bottle of sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution and required water at least two hours prior to colonoscopy.

DOSAGE FORMS & STRENGTHS SECTION

3 DOSAGE FORMS & STRENGTHS

• Sodium sulfate, potassium sulfate and magnesium sulfate oral solution**(for adults):**Two bottles each containing 6 ounces of an oral solution of 17.5 grams sodium sulfate, 3.13 grams potassium sulfate, and 1.6 grams magnesium sulfate as a clear to slightly hazy liquid.

When diluted as directed, the solution is clear and colorless.

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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CONTRAINDICATIONS SECTION

Highlight: * 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)

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 Precaution (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

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USE IN SPECIFIC POPULATIONS SECTION

8 USE IN SPECIFIC POPULATIONS

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 (sodium sulfate, potassium sulfate and magnesium sulfate oral solution).

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.

8.2 Lactation

Risk Summary

There are no data available data on the presence of sodium sulfate, potassium sulfate and magnesium sulfate oral solution in human or animal milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sodium sulfate, potassium sulfate and magnesium sulfate oral solution and any potential adverse effects on the breastfed child from sodium sulfate, potassium sulfate and magnesium sulfate oral solution or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of sodium sulfate, potassium sulfate and magnesium sulfate oral solution in pediatric patients less than 12 years of age have not been established.

****Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

8.5 Geriatric Use

Of the 375 patients who received sodium sulfate, potassium sulfate and magnesium sulfate oral solution in clinical trials, 94 (25%) were 65 years of age or older, and 25 (7%) were 75 years of age or older. No overall differences in safety or effectiveness of sodium sulfate, potassium sulfate and magnesium sulfate oral solution, administered as the recommended split- dose (2-day) regimen, were observed between geriatric patients and younger patients. Geriatric patients reported more vomiting when sodium sulfate, potassium sulfate and magnesium sulfate oral solution was given as a one-day preparation (not a recommended regimen).

Elderly patients are more likely to have decreased hepatic, renal or cardiac function and may be more susceptible to adverse reactions resulting from fluid and electrolyte abnormalities [see Warnings and Precautions (5.1)].

8.6 Renal Impairment

Use sodium sulfate, potassium sulfate and magnesium sulfate oral solution with caution in patients with renal impairment or patients taking concomitant medications that may affect renal function. These patients may be at risk for renal injury. Advise these patients of the importance of adequate hydration before, during and after use of sodium sulfate, potassium sulfate and magnesium sulfate oral solution and consider performing baseline and post- colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Warnings and Precautions (5.4)].

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ADVERSE REACTIONS SECTION

Highlight: Most common adverse reactions are:

• Adults (>2%): overall discomfort, abdominal distention, abdominal pain, nausea, and vomiting. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or****www.fda.gov/medwatch.

6 ADVERSE REACTIONS

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)]

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.

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*

• 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

1The study was not designed to support comparative claims for the laboratory abnormalities reported in this table.

2Percent (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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution in an evening-only (1-day) dosing regimen is not recommended.

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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OVERDOSAGE SECTION

10 OVERDOSAGE

Overdosage of more than the recommended dose of sodium sulfate, potassium sulfate and magnesium sulfate oral solution may lead to severe electrolyte disturbances, as well as dehydration and hypovolemia, with signs and symptoms of these disturbances. [see Warnings and Precautions (5.1, 5.2, 5.3)]. Monitor for fluid and electrolyte disturbances and treat symptomatically.

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INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide).

Instruct patients or caregivers:

• Must dilute sodium sulfate, potassium sulfate and magnesium sulfate oral solution 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, apple or orange juice without pulp, lemonade, coffee, tea, or chicken broth). On the day of the colonoscopy only consume clear liquids up to two hours prior to colonoscopy.
• Two doses of sodium sulfate, potassium sulfate and magnesium sulfate oral solution are required for a complete preparation for colonoscopy. One bottle of sodium sulfate, potassium sulfate and magnesium sulfate oral solution is equivalent to one dose.
• Do not to take other laxatives while taking sodium sulfate, potassium sulfate and magnesium sulfate oral solution.
• Do not eat solid food or drink milk or eat or drink anything colored red or purple.
• Do not drink alcohol.
• 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 colonoscopy.
• Contact their healthcare provider if they develop significant vomiting or signs of dehydration after taking sodium sulfate, potassium sulfate and magnesium sulfate oral solution or if they experience cardiac arrhythmias or seizures [see Warnings and Precautions (5.1, 5.2, 5.3)].

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Manufactured by:

Alkem Laboratories Ltd.,

INDIA.

Distributed by:

Ascend Laboratories, LLC

Parsippany, NJ 07054

Revised: December, 2022

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

Each sodium sulfate, potassium sulfate, and magnesium sulfate oral solution (for adults)(NDC 67877-725-92) contains:

• Two bottles (NDC 67877-725-82) each containing 6-ounces of an oral solution of 17.5 grams sodium sulfate, 3.13 grams potassium sulfate, and 1.6 grams magnesium sulfate as a clear to slightly hazy liquid. When diluted as directed, the solution is clear and colorless.
• One (1) mixing container with a 16-ounce fill line.

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F). [see USP Controlled Room Temperature].

Pediatric use information is approved for Braintree Laboratories, Inc.’s SUPREP BOWEL PREP KIT (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution. However, due to Braintree Laboratories, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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