may not be absorbed properly.

e, and bun). fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias, seizures and renal impairment. patients with electrolyte abnormalities should have them corrected before treatment with sodium sulfate, potassium sulfate and magnesium sulfate oral solution. in addition, 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 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). pre-dose and post-colonoscopy ecgs should be considered 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. 5.4 renal impairment use caution when prescribing sodium sulfate, potassium sulfate and magnesium sulfate oral solution for 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). advise these patients of the importance of adequate hydration, and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and bun) in these patients. 5.5 colonic mucosal ulcerations and ischemic colitis administration of 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution may increase these risks. the potential for mucosal ulcerations resulting from the bowel preparation should be considered 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 sodium sulfate, potassium sulfate and magnesium sulfate oral solution. use with caution in patients with severe active ulcerative colitis. 5.7 aspiration use with caution in patients with impaired gag reflex and patients prone to regurgitation or aspiration. such patients should be observed during administration of sodium sulfate, potassium sulfate and magnesium sulfate oral solution. 5.8 not for direct ingestion each bottle must be diluted with water to a final volume of 16 ounces and ingestion of additional water as recommended is important to patient tolerance. direct ingestion of the undiluted solution may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances.

o bottles) is 3 quarts (approximately 2.8 l) taken orally prior to the colonoscopy in the following way: split-dose (two-day) regimen day prior to colonoscopy: a light breakfast may be consumed, or have only clear liquids on the day before colonoscopy. avoid red and purple liquids, milk, and alcoholic beverages. early in the evening prior to colonoscopy: pour the contents of one bottle of sodium sulfate, potassium sulfate and magnesium sulfate oral solution into the mixing container provided. fill the container with water to the 16 ounce fill line, and drink the entire amount. drink two additional containers filled to the 16 ounce line with water over the next hour. day of colonoscopy: have only clear liquids until after the colonoscopy. avoid red and purple liquids, milk, and alcoholic beverages. the morning of colonoscopy (10 to 12 hours after the evening dose): pour the contents of the second bottle of sodium sulfate, potassium sulfate and magnesium sulfate oral solution into the mixing container provided. fill the container with water to the 16 ounce fill line, and drink the entire amount. drink two additional containers filled to the 16 ounce line with water over the next hour. complete all sodium sulfate, potassium sulfate and magnesium sulfate oral solution and required water at least two hours prior to colonoscopy or as directed by physician.

inal 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.

may not be absorbed properly.

lfate 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.

-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 c max , followed by the hepatic impairment group, and then by healthy subjects. systemic exposure of serum sulfate (auc and c max ) was similar between healthy subjects and hepatic impairment patients. renal impairment resulted in 54% higher mean auc and 44% higher mean c max 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.

ent resulted in 54% higher mean auc and 44% higher mean c max 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.

atremia, 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.

al 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 responders 1 % ( 95 % c . i .) sodium sulfate , potassium sulfate and magnesium sulfate oral solution – peg difference ( 95 % ci ) sodium sulfate, potassium sulfate and magnesium sulfate oral solution (with light breakfast) split- dose 180 97 % (94%, 99%) 2 % 2 (-2%, 5%) peg bowel prep (with normal breakfast & light lunch) 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 amounts of feces or fluid not interfering with the exam) by the colonoscopist. 2 does not equal difference in tabled responder rates due to rounding effects.