The following serious or otherwise important adverse reactions for bowel preparations are described elsewhere in the labeling: Serious Fluid and Electrolyte Abnormalities [see Warnings and Precautions ( 5.1 )] Cardiac Arrhythmias [see Warnings and Precautions ( 5.2 )] Seizures [see Warnings and Precautions ( 5.3 )] 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 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Risk of Gastrointestinal Complications with Ingestion of Desiccant [see Warnings and Precautions ( 5.8 )] Most common gastrointestinal adverse reactions are nausea, abdominal distension, vomiting and upper abdominal pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Braintree Laboratories, Inc. at 1-800-874-6756 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials 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. 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 Total Number of Patients per Treatment Arm (N) 281 271 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 Total Number of Patients per Treatment Arm (N) 190 199 Patients with at Least One Gastrointestinal Adverse Reaction from Symptom Questionnaire 135 67 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.
6.2Postmarketing 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 )]
