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Suclear

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Suclear

CLINICAL PHARMACOLOGY

Mechanism of Action

The primary mode of action of Suclear is the osmotic effect of the unabsorbed polyethylene glycol (PEG) and sulfate salts. 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.

PEG is also a largely unabsorbed osmotic agent which causes water to be retained within the gastrointestinal tract.

Pharmacodynamics

The osmotic effect of the unabsorbed PEG or sulfate ions, when ingested, produces a copious watery diarrhea.

Pharmacokinetics

Oral sulfates: Following oral administration of oral sulfate solution, approximately 20% of dose undergoes systemic absorption, with the remainder of the dose excreted in feces. Renal elimination appears to be the predominant route of clearance for absorbed sulfate. After administration of Suclear (only the 6-oz bottle of sulfate salts) to six healthy volunteers, the time at which serum sulfate reached its highest point (Tmax) was approximately 5.5 hours after the first dose of sulfates. Serum sulfate levels declined with a half-life of 8.5 hours.

PEG3350: The pharmacokinetics of PEG3350 following administration of Suclear were not assessed. Available pharmacokinetic information for oral PEG3350 suggests that it is poorly absorbed, primarily excreted in feces, and, to the extent it is absorbed it is eliminated in urine.

Pharmacokinetic Studies in Patients with Hepatic Impairment or Renal Impairment

The disposition of sulfate after ingestion of one 6-oz bottle of the Suclear sulfate solution was studied in patients (N=6) with mild-moderate hepatic impairment [Child-Pugh grades A (n = 5) and B (n = 1)] and in patients (N=6) with moderate renal impairment (creatinine clearance of 30 to 49 mL/min). Following administration of one 6-oz dose of sulfates, the renal impairment group had the highest serum sulfate levels, followed by the hepatic impairment group, and then by healthy subjects. Renal impairment resulted in 43% higher mean Cmax than healthy subjects. Urinary excretion of sulfate over 30 hours in subjects who received two 6-oz doses of sulfates was similar between hepatic patients and normal volunteers, but was approximately 16% lower in moderate renal impairment patients than in healthy volunteers. The mean sulfate levels of all three groups returned to their respective baseline levels by Day 6 after dose initiation.

PK for PEG3350 at the recommended dose was not assessed in patients with organ impairment.

Animal Toxicology and/or Pharmacology

The sulfate salts of sodium, potassium, and magnesium contained in Suclear were administered orally (gavage) to rats and dogs up to 28 days up to a maximum daily dose of 5 g/kg/day (approximately 1.8 and 6 times for rats and dogs, respectively, the recommended human dose of 22 g/day or 0.44 g/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, abnormal excreta (soft and/or mucoid feces and/or diarrhea) and increased urine pH and sodium excretion.

Clinical Studies

The colon cleansing efficacy of Suclear was evaluated in two randomized, single-blind (colonoscopist only), active-controlled, multicenter studies (Studies 1 and 2) in patients scheduled to undergo an elective colonoscopy. A total of 737 adult patients were included in the efficacy analysis: 366 from Study 1 and 371 from Study 2. Patients ranged in age from 21 to 86 years (mean age 57 years), and 54% were female. Self-identified race distribution was as follows: 82% White, 10% Black, and 8% other.

Patients randomized to Suclear in the two studies were treated with one of two dosing regimens:

  • In Study 1, Suclear was given by “Day-Before” (evening before) dosing, where both doses were taken sequentially on the day before the colonoscopy, with the first dose taken at approximately 6:00 PM, followed by one 16-oz container (provided with the kit) of water, and the second dose taken 2 hours after starting the first dose. Patients were recommended to drink at least one additional 16-oz container of water on the evening prior to colonoscopy.
    The comparator for Study 1 was a preparation containing two liters of PEG plus electrolytes (sodium chloride, sodium bicarbonate, and potassium chloride) for oral solution and two 5-mg bisacodyl tablets, administered the day before the procedure. All patients in both the Suclear and comparator group were limited to a clear liquid diet on the day before the procedure until after completion of the colonoscopy.
  • In Study 2, Suclear was given by “Split-Dose” (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (at approximately PM), followed by one 16-oz container of water (with a recommendation to drink at least one additional 16-oz container of water on the evening prior to colonoscopy), and the second dose was taken the morning of the colonoscopy (at approximately AM). The second dose had to be completed at least 2 hours prior to colonoscopy. Patients in the Suclear group were limited to a clear liquid diet on the day before the procedure until after completion of the colonoscopy.
    The comparator for Study 2 was a preparation containing two liters of PEG plus electrolytes (sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid) for oral solution, administered as split doses. Patients receiving Suclear were limited to a clear liquid diet on the day before the procedure until completion of the colonoscopy. Patients receiving the comparator were allowed to have a normal breakfast, a light lunch, clear soup and/or plain yogurt for dinner the day prior to colonoscopy. They were limited to a clear liquid diet from the time the preparation was started until after completion of the colonoscopy.

The primary efficacy endpoint in both studies was the proportion of patients with successful colon cleansing as assessed by the colonoscopists, who were not informed about the type of preparation received. Successful colon cleansing was defined as bowel preparations that were graded excellent (no more than small bits of adherent feces/fluid) or good (small amounts of feces or fluid not interfering with the exam) by the colonoscopist. Failed colon cleansing was defined as bowel preparations that were graded fair (enough feces or fluid to prevent a completely reliable exam) or poor (large amounts of fecal residue, additional cleansing required). The proportion of patients with successful colon cleansing was numerically similar between treatment groups for both studies. See Tables 3 and 4.

Table 3: Proportion of Patients with Successful Colon Cleansing† in Study 1 (Day-Before Regimen)

Suclear Comparator 1‡ Difference between treatment groups
% (n/N) 95% CI % (n/N) 95% CI Difference 95% CI
90% (158/176) (84%, 94%) 84% (157/188) (77%, 89%) 6% (-1%, 13%)
†Successful colon cleansing was defined as excellent (no more than small bits of adherent feces/fluid) or good (small amounts of feces or fluid not interfering with the exam) by the blinded colonoscopist.
‡Comparator 1: PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution; and two bisacodyl 5-mg delayed-release tablets.

Table 4: Proportion of Patients with Successful Colon Cleansing in Study 2 (Split-Dose Regimen)

Suclear Comparator 2‡ Difference between treatment groups
% (n/N) 95% CI % (n/N) 95% CI Difference 95% CI
94% (173/185) (89%, 97%) 94% (173/185) (89%, 97%) 0% (-5%, 5%)
†Successful colon cleansing was defined as excellent (no more than small bits of adherent feces/fluid) or good (small amounts of feces or fluid not interfering with the exam) by the blinded colonoscopist.
‡Comparator 2: PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid for oral solution.

Last reviewed on RxList: 2/1/2013
This monograph has been modified to include the generic and brand name in many instances.

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