6 ADVERSE REACTIONS Most common adverse reactions (≥3%) are: overall discomfort, abdominal fullness, nausea, abdominal cramping, and vomiting (6) 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 . 6.1 Clinical Studies 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. In a multicenter, controlled clinical trial comparing SUPREP Bowel Prep Kit with a bowel prep containing polyethylene glycol and electrolytes (PEG + E) that were administered in a split-dose (2-day) regimen, the most common adverse reactions after administration of SUPREP Bowel Prep Kit were overall discomfort, abdominal 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 SUPREP Bowel Prep Kit 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 SUPREP 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 SUPREP Bowel Prep Kit 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 *Percent (n/N) of patients where N=number of patients with normal baseline who had abnormal values at the timepoint(s) of interest. †Patients with normal bicarbonate at baseline who developed low bicarbonate (≤ 21 mEq/L) and high anion gap (≥ 13 mEq/L) on Day of Colonoscopy or Day 30. Day of Colonoscopy n (%)* Day 30 n (%)* Anion gap (high) † SUPREP 14 (8.9) 3 (1.9) PEG + Electrolytes 12 (7.6) 2 (1.4) Bicarbonate (low) SUPREP 20 (12.7) 7 (4.4) PEG + Electrolytes 24 (15.2) 4 (2.7) Bilirubin, total (high) SUPREP 14 (8.5) 0 (0) PEG + Electrolytes 20 (11.7) 3 (1.9) BUN (high) SUPREP 2 (1.6) 14 (11.2) PEG + Electrolytes 4 (2.9) 19 (14.5) Calcium (high) SUPREP 16 (10.4) 8 (5.2) PEG + Electrolytes 6 (3.7) 6 (3.9) Chloride (high) SUPREP 4 (2.4) 6 (3.7) PEG + Electrolytes 20 (12.2) 6 (3.8) Creatinine (high) SUPREP 3 (1.9) 5 (3.2) PEG + Electrolytes 2 (1.2) 8 (5.2) Osmolality (high) SUPREP 8 (5.8) NA PEG + Electrolytes 19 (12.9) NA Osmolality (low) SUPREP 3 (2.2) NA PEG + Electrolytes 2 (1.4) NA Potassium (high) SUPREP 3 (1.8) 6 (3.7) PEG + Electrolytes 5 (2.9) 8 (4.9) Sodium (low) SUPREP 5 (3.1) 1 (0.6) PEG + Electrolytes 4 (2.3) 2 (1.2) Uric acid (high) SUPREP 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 SUPREP Bowel Prep Kit 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 SUPREP Bowel Prep Kit 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 SUPREP Bowel Prep Kit, 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 SUPREP Bowel Prep Kit split-dose (2day) regimen. Administration of SUPREP Bowel Prep Kit in an evening-only (1-day) dosing regimen is not recommended.