laxatives and sutab may increase the risk of mucosal ulceration or ischemic colitis. avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking sutab [see warnings and precautions ( 5.5 )] .

ylaxis : inform patients to seek immediate medical care if symptoms occur. ( 5.7 ) 5.1 serious fluid and electrolyte abnormalities advise all patients to hydrate adequately before, during, and after the use of sutab. if a patient develops significant vomiting or signs of dehydration after taking sutab, 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 sutab. use sutab 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 )] 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 sutab 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 sutab 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 sutab with caution in 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) [see drug interactions ( 7.1 )] . these patients may be at risk for renal injury. advise these patients of the importance of adequate hydration with sutab and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and bun) in these patients [see use in specific populations ( 8.6 )] . 5.5 colonic mucosal ulcerations and ischemic colitis osmotic laxative products may produce colonic mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. in addition, gastric ulcerations or gastritis may occur. concurrent use of stimulant laxatives and sutab may increase these risks [see drug interactions ( 7.3 )] . consider the potential for mucosal ulcerations resulting from the bowel preparation 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 sutab [see contraindications ( 4 )] . use in caution in patients with severe active ulcerative colitis. 5.7 hypersensitivity reactions serious hypersensitivity reactions, including anaphylaxis, angioedema, dyspnea, rash, pruritis and urticaria have been reported with sutab [see adverse reactions ( 6.2 )] . inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur.

re amount over 15 to 20 minutes. o approximately one hour after the last tablet is ingested, fill the provided container a second time with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. o approximately 30 minutes after finishing the second container of water, fill the provided container with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. morning of the colonoscopy: o open 1 bottle of 12 tablets. o fill the provided container with 16 ounces of water (up to the fill line). swallow each tablet with a sip of water and drink the entire amount over 15 to 20 minutes. o approximately one hour after the last tablet is ingested, fill the provided container a second time with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. o approximately 30 minutes after finishing the second container of water, fill the provided container with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. o complete all sutab tablets and required water at least 2 hours before colonoscopy. 2.1 preparation and administration instructions correct fluid and electrolyte abnormalities before treatment with sutab [see warnings and precautions ( 5.1 )] administration of two doses of sutab (24 tablets) are required for a complete preparation for colonoscopy. twelve (12) tablets are equivalent to one dose. water must be consumed with each dose of sutab and additional water must be consumed after each dose. consume a low residue breakfast on the day before colonoscopy, followed by clear liquids up to 2 hours prior to colonoscopy. do not drink milk or eat or drink anything colored red or purple. do not drink alcohol. do not take other laxatives while taking sutab. do not take oral medications within 1 hour of starting each dose of sutab. 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 each dose of sutab. stop consumption of all fluids at least 2 hours prior to the colonoscopy. 2.2 split-dose (2-day) regimen the recommended split-dose regimen for adults consists of two doses of sutab: the first dose during the evening prior to colonoscopy and the second dose the next day, during the morning of the colonoscopy. instruct patients: dose 1 – on the day prior to colonoscopy : a low residue breakfast may be consumed. examples of low residue foods are eggs, white bread, cottage cheese, yogurt, grits, coffee, tea. after breakfast, only clear liquids may be consumed until after the colonoscopy. early in the evening prior to colonoscopy, open one bottle of 12 tablets. fill the provided container with 16 ounces of water (up to the fill line). swallow each tablet with a sip of water and drink the entire amount over 15 to 20 minutes. approximately one hour after the last tablet is ingested, fill the provided container a second time with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. approximately 30 minutes after finishing the second container of water, fill the provided container again with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. if patients experience preparation-related symptoms (e.g. nausea, bloating, cramping), pause or slow the rate of drinking the additional water until symptoms diminish. dose 2 - day of colonoscopy : continue to consume only clear liquids until after the colonoscopy. the morning of colonoscopy (5 to 8 hours prior to the colonoscopy and no sooner than 4 hours from starting dose 1), open the second bottle of 12 tablets. fill the provided container with 16 ounces of water (up to the fill line). swallow each tablet with a sip of water and drink the entire amount over 15 to 20 minutes. approximately one hour after the last tablet is ingested, fill the provided container a second time with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. approximately 30 minutes after finishing the second container of water, fill the provided container again with 16 ounces of water (up to the fill line) and drink the entire amount over 30 minutes. if patients experience preparation-related symptoms (e.g. nausea, bloating, cramping), pause or slow the rate of drinking the additional water until symptoms diminish. complete all sutab tablets and water at least two hours prior to colonoscopy.

idely 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. the safety of sutab was evaluated in two randomized, parallel group, multicenter, investigator blinded clinical trials in 941 adult patients undergoing colonoscopy. the active comparators were polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, ascorbic acid and sodium ascorbate for oral solution in study 1 and sodium picosulfate, magnesium oxide, and anhydrous citric acid for oral solution in study 2 [see clinical studies ( 14 )] . adverse gastrointestinal reactions reported by symptom questionnaire in studies 1 and 2, patients were queried for selected gastrointestinal adverse reactions of stomach cramping (upper abdominal pain), stomach bloating (abdominal distention), nausea and vomiting using a standard questionnaire following completion of study drug and prior to colonoscopy on the day of colonoscopy. patients reporting selected gastrointestinal symptom(s) rated the intensity as mild, moderate or severe. a total of 52% (287/552) of patients in study 1 and 52% (202/389) in study 2 reported at least one selected gastrointestinal adverse reaction when queried using the standard questionnaire. tables 1 and 2 show results for each gastrointestinal adverse reaction reported by patients using the standard questionnaire, including severity. table 1: gastrointestinal symptoms by severity a from symptom questionnaire in adult patients following colon cleansing and prior to colonoscopy – study 1 b a mild : barely noticeable, does not influence functioning causing no limitations of usual activities; moderate : makes participant uncomfortable, influences functioning causing some limitations of usual activities; severe : severe discomfort, treatment needed, severe and undesirable, causing inability to carry out usual activities b study 1 was not designed to support comparative claims for sutab for the adverse reactions reported in this table. c percentage represents n/n for patients who experienced each gastrointestinal adverse reaction on the symptom questionnaire based on the total number of patients per treatment arm. symptom sutab polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, ascorbic acid and sodium ascorbate total number or patients per treatment arm (n) 281 271 patients with at least one gastrointestinal adverse reaction from symptom questionnaire 163 124 % nausea c 48 26 mild 71 77 moderate 27 23 severe 2 0 % abdominal distension c,d 29 22 mild 68 71 moderate 30 29 severe 1 0 % vomiting c 23 5 mild 48 46 moderate 52 54 severe 0 0 % upper abdominal pain c 16 18 mild 65 71 moderate 35 29 severe 0 0 table 2: gastrointestinal symptoms by severity a from symptom questionnaire in adult patients following colon cleansing and prior to colonoscopy – study 2 b a mild : barely noticeable, does not influence functioning causing no limitations of usual activities; moderate : makes participant uncomfortable, influences functioning causing some limitations of usual activities; severe : severe discomfort, treatment needed, severe and undesirable, causing inability to carry out usual activities b study 2 was not designed to support comparative claims for sutab for the adverse reactions reported in this table. c percentage represents n/n for patients who experienced each gastrointestinal adverse reaction on the symptom questionnaire based on the total number of patients per treatment arm. symptom sutab sodium picosulfate, magnesium oxide, and anhydrous citric acid total number or patients per treatment arm (n) 190 199 patients with at least one gastrointestinal adverse reaction from symptom questionnaire 135 67 % nausea c 52 18 mild 74 94 moderate 20 6 severe 6 0 % abdominal distension c 34 15 mild 73 69 moderate 27 31 severe 0 0 % vomiting c 16 2 mild 53 33 moderate 47 67 severe 0 0 % upper abdominal pain c 23 13 mild 82 100 moderate 16 0 severe 2 0 additional adverse reactions reported in studies 1 and 2 in addition to the gastrointestinal symptoms reported on the standard questionnaire (tables 1 and 2), other adverse reactions reported in at least 2% of patients in either treatment arm in studies 1 and 2 were: dizziness in study 1 (0% sutab and 2% comparator); and hypermagnesemia (2% sutab and 2% comparator) and increased liver function test (including alt, ast and bilirubin) (3% sutab and 1% comparator) in study 2. laboratory changes electrolyte abnormalities shifts in serum electrolytes from normal at baseline to above the upper end of normal following study drug on the day of colonoscopy in at least 2% of patients in either treatment arm and at least 2% greater in patients treated with sutab than treated with comparator in either study 1 or study 2 were: magnesium (27% sutab and 5% comparator in study 1), and serum osmolality (44% sutab and 28% comparator in study 2). these changes were transient and resolved without intervention. renal function parameters decreases in creatinine clearance and increases in blood urea nitrogen (bun) were reported in less than 1% of patients in both sutab and comparator arms in both trials. 6.2 postmarketing experience the following adverse reactions have been identified during post-approval use of sutab. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. gastrointestinal : gastric ulceration, gastritis hypersensitivity : anaphylaxis, angioedema, dyspnea, rash, pruritus, urticaria [see warnings and precautions ( 5.7 )]

laxatives and sutab may increase the risk of mucosal ulceration or ischemic colitis. avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking sutab [see warnings and precautions ( 5.5 )] .

nsidered along with the mother’s clinical need for sutab and any potential adverse effects on the breastfed child from sutab or from the underlying maternal condition. 8.4 pediatric use safety and effectiveness in pediatric patients have not been established. 8.5 geriatric use of the 471 patients who received sutab in pivotal clinical trials, 150 (32%) were 65 years of age or older, and 25 (5%) were 75 years of age or older. no differences in safety or effectiveness of sutab were observed between geriatric patients and younger patients. 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 sutab 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 sutab and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and bun) in these patients [see warning and precautions ( 5.4 )] .

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 a sulfate-based product containing sodium sulfate, potassium sulfate, and magnesium sulfate similar to sutab was also studied in patients (n=6) with mild-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.

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.

ration ( 2.2 )] . patients receiving sutab were limited to a low residue breakfast followed by clear liquids on the day prior to the day of colonoscopy; patients receiving the comparator bowel prep were allowed to have a normal breakfast and a light lunch, followed by clear liquids and/or yogurt for dinner. approximately 97% of patients in the study completed both doses of preparation (98% of sutab patients and 95% of comparator patients). in study 2 (bli4700-302; nct 03261960), 388 adult patients were included in the efficacy analysis. patients ranged in age from 23 to 83 years (median age 58 years) and 58% were female. racial distribution was 94% caucasian, 9% hispanic or latino, and 5% african-american. patients were randomized to one of the following two colon preparation regimens: sutab or sodium picosulfate, magnesium oxide, and anhydrous citric acid for oral solution. both preparations were administered according to a split-dose regimen [see dosage and administration ( 2.2 )] . patients receiving sutab were limited to a low residue breakfast followed by clear liquids on the day prior to the day of colonoscopy; patients receiving the comparator bowel prep were only allowed clear liquids on the day prior to colonoscopy. approximately 98% of patients in the study completed both doses of preparation (98% of sutab patients and 99% of comparator patients). the primary efficacy endpoint in each trial was the proportion of patients with successful colon cleansing, as assessed by the blinded colonoscopist utilizing the four-point scaled described below. success was defined as an overall cleansing assessment of 3 (good) or 4 (excellent). score grade description 1 poor large amount of fecal residue, additional bowel preparation required. 2 fair enough feces even after washing and suctioning to prevent clear visualization of the entire colonic mucosa. 3 good feces and fluid requiring washing and suctioning, but still achieves clear visualization of the entire colonic mucosa. 4 excellent no more than small bits of feces/fluid which can be suctioned easily; achieves clear visualization of the entire colonic mucosa. results for the primary endpoint in studies 1 and 2 are shown in table 3. in both trials, sutab was non-inferior to the comparator. table 3 proportion of adult patients with overall cleansing success a in two controlled trials with a split-dose regimen a success was defined as an overall cleaning assessment of 3 (good) or 4 (excellent) by the blinded endoscopist, scores were assigned on withdrawal of colonoscope. b treatment differences and confidence intervals were adjusted by study sites based on mantel-haenszel method c comparator in study 1 was polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution d comparator in study 2 was sodium picosulfate, magnesium oxide, and anhydrous citric acid for oral solution e non-inferior sutab % (n/n) comparator % (n/n) sutab-comparator difference b (%) 99% confidence interval b study 1 92% (257/278) 89% c (241/270) 3.0 (-3.2, 9.3) e study 2 92% (175/190) 88% d (174/198) 3.1 (-4.5, 10.7) e

dose of sutab. to complete all sutab tablets and required water at least two hours prior to colonoscopy. to contact their healthcare provider if they develop significant vomiting or signs of dehydration after taking sutab or if they experience cardiac arrhythmias or seizures [see warnings and precautions ( 5.1 , 5.2 , 5.3 )] . to seek immediate medical care should signs or symptoms of a hypersensitivity reaction occur [see warnings and precautions ( 5.7 )] manufactured by: braintree laboratories, inc. 270 centre street holbrook, ma 02343 this product is covered by the following patents: u.s. patents 10,143,656, 11,033,498 please see www.sebelapharma.com for patent information. © braintree laboratories, inc.