SODIUM SULFATE, POTASSIUM SULFATE, MAGNESIUM SULFATE (Page 2 of 4)
7 DRUG INTERACTIONS
7.1 Drugs That May Increase Risks Due to Fluid and Electrolyte Abnormalities
Use caution when prescribing Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution 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 (5)] in patients taking these concomitant medications.
7.2 Potential for Altered Drug Absorption
Oral medication administered within one hour of the start of each Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution dose may be flushed from the gastrointestinal tract, and the medication may not be absorbed properly.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic effects: Pregnancy Category C. Animal reproduction studies have not been conducted with Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. It is also not known whether Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution should be given to a pregnant 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 Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
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 a 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.
11 DESCRIPTION
Each Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution contains two 6 ounce bottles of solution. Each 6 ounce bottle contains: sodium sulfate 17.5 grams, potassium sulfate 3.13 grams, magnesium sulfate 1.6 grams. Inactive ingredients include: sodium benzoate, sucralose, malic acid, citric acid, lemon flavor, purified water. The solution is a clear to slightly hazy liquid. The solution is clear and colorless when diluted to a final volume of 16 ounces with water.
Sodium Sulfate, USP
The chemical name is Na2 SO4 . The average Molecular Weight is 142.04. The structural formula is:
Potassium Sulfate, FCC, Granular
The chemical name is K2 SO4 . The average Molecular Weight is 174.26. The structural formula is:
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 package also contains a polypropylene mixing container.
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
The osmotic effect of the unabsorbed ions, when ingested with a large volume of water, produces a copious watery diarrhea.
12.3 Pharmacokinetics
Fecal excretion was the primary route of sulfate elimination. After administration of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution in six healthy volunteers, the time at which serum sulfate reached its highest point (Tmax) was approximately 17 hours after the first half dose or approximately 5 hours after the second dose, and then declined with a half-life of 8.5 hours.
The disposition of sulfate after Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution was also studied in patients (N=6) with mild-moderate hepatic impairment (Child-Pugh grades A and B) and in patients (N=6) with moderate renal impairment (creatinine clearance of 30 to 49 mL/min). The renal impairment group had the highest serum sulfate AUC and Cmax , followed by the hepatic impairment group, and then by healthy subjects. Systemic exposure of serum sulfate (AUC and Cmax ) was similar between healthy subjects and hepatic impairment patients. Renal impairment resulted in 54% higher mean AUC and 44% higher mean Cmax than healthy subjects. The mean sulfate levels of all three groups returned to their respective baseline levels by Day 6 after dose initiation. Urinary excretion of sulfate over 30 hours, starting after the first half dose, was similar between hepatic patients and normal volunteers, but was approximately 16% lower in moderate renal impairment patients than in healthy volunteers.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution. Studies to evaluate the possible impairment of fertility or mutagenic potential of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution have not been performed.
13.2 Animal Toxicology and/or Pharmacology
The sulfate salts of sodium, potassium, and magnesium contained in Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution were administered orally (gavage) to rats and dogs up to 28 days up to a maximum daily dose of 5 grams/kg/day (approximately 0.9 and 3 times for rats and dogs, respectively, the recommended human dose of 44 grams/day or 0.89 grams/kg based on the body surface area). In rats, the sulfate salts caused diarrhea and electrolyte and metabolic changes, including hypochloremia, hypokalemia, hyponatremia, lower serum osmolality, and high serum bicarbonate. Significant renal changes included increased fractional sodium excretion, increased urinary sodium and potassium excretion, and alkaline urine in both males and females. In addition, creatinine clearance was significantly decreased in females at the highest dose. No microscopic renal changes were seen. In dogs, the sulfate salts caused emesis, excessive salivation, excessive drinking of water, and abnormal excreta (soft and/or mucoid feces and/or diarrhea) and increased urine pH and sodium excretion.
14 CLINICAL STUDIES
The colon cleansing efficacy of Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution was evaluated in a randomized, single-blind, active-controlled, multicenter study. In this study, 363 adult patients were included in the efficacy analysis. Patients ranged in age from 20 to 84 years (mean age 55 years) and 54% were female. Race distribution was 86% Caucasian, 9% African-American, and 5% other.
Patients were randomized to one of the following two colon preparation regimens: Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution or a marketed polyethylene glycol (PEG) bowel prep. In the Study Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution was administered according to a split-dose preparation regimen [see Dosage and Administration (2)]. The PEG bowel prep was also given as a split-dose preparation according to its labeled instructions. Patients receiving Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution were limited to a light breakfast followed by clear liquids on the day prior to the day of colonoscopy; patients receiving the PEG bowel prep were allowed to have a normal breakfast and a light lunch, followed by clear liquids.
The primary efficacy endpoint was the proportion of patients with successful colon cleansing as assessed by the colonoscopists, who were not informed about the type of preparation received. In the study, no clinically or statistically significant differences were seen between the group treated with Sodium Sulfate, Potassium Sulfate and Magnesium Sulfate Oral Solution and the group treated with the PEG bowel prep. See Table 3 below.
| Table 3 : Colon Cleansing Response Rates | ||||
| Treatment Group | Regimen | N | Responders1 % ( 95 % C . I .) | Sodium Sulfate , Potassium Sulfate and Magnesium Sulfate Oral Solution – PEG Difference ( 95 % CI ) |
| Sodium Sulfate, PotassiumSulfate and Magnesium SulfateOral Solution (With lightbreakfast) | Split-Dose | 180 | 97 %(94%, 99%) | 2 %2 (-2%, 5%) |
| PEG bowel prep(with normal breakfast & lightlunch) | Split-Dose | 183 | 96 %(92%, 98%) | |
| 1 Responders were patients whose colon preparations were graded excellent (no more than small bits of adherent feces/fluid) or good (small amountsof feces or fluid not interfering with the exam) by the colonoscopist. | ||||
| 2 Does not equal difference in tabled responder rates due to rounding effects. | ||||
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