1 INDICATIONS AND USAGE PLENVU ® is indicated for cleansing of the colon in preparation for colonoscopy in adults.

PLENVU is an osmotic laxative indicated for cleansing of the colon in preparation for colonoscopy in adults.

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6 ADVERSE REACTIONS 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 Renal Impairment [see Warnings and Precautions ( 5.4 )] • Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis [see Warnings and Precautions ( 5.5 )] • Patients with Significant Gastrointestinal Disease [see Warnings and Precautions ( 5.6 )] • Aspiration [see Warnings and Precautions ( 5.7 )] • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency [see Warnings and Precautions ( 5.8 )] • Risks in Patients with Phenylketonuria [see Warnings and Precautions ( 5.9 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.10 )] Most common adverse reactions (>2%) are nausea, vomiting, dehydration and abdominal pain/discomfort.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of PLENVU Two-Day Split Dosage and One-Day Morning Dosage regimens was evaluated in two randomized, parallel group, multicenter, investigator-blinded clinical trials (Two-Day Split Dosage in the NOCT and MORA trials and One-Day Morning Dosage in the MORA trial) in 1351 adult patients undergoing colonoscopy.

The mean age of the study population was 56 years (range 18 to 86 years), 92% of patients were Caucasian and 51% were female.

In the NOCT trial, 61% of patients had mild renal impairment.

In the MORA trial, 67% had mild renal impairment and 5% had moderate renal impairment.

Patients with severe renal impairment were not enrolled in the clinical trials of PLENVU [see Clinical Studies ( 14 )].

The most common adverse reactions (>2%) in the PLENVU treatment groups in both trials were: nausea, vomiting, dehydration and abdominal pain/discomfort.

Table 1 and Table 2 display adverse reactions reported in at least 1% of patients in one or more treatment group(s) in the NOCT and MORA trials, respectively.

Since diarrhea was considered as a part of the efficacy assessment, it was not defined as an adverse reaction in these trials.

Table 1: Common Adverse Reactions* in Patients Undergoing Colonoscopy in the NOCT Trial by Treatment Group Preferred Term PLENVU Two-Day Split Dosage Regimen (N = 275) % Trisulfate Trisulfate: Two 6-ounce bottles of oral solution each containing sodium sulfate 17.5 grams, potassium sulfate 3.13 grams, magnesium sulfate 1.6 grams Two-Day Split Dosage Regimen (N = 271) % Nausea 7 2 Vomiting 6 3 Dehydration Includes signs and symptoms of dehydration, including dizziness, dry mouth, orthostatic hypotension, pre-syncope, syncope, and thirst 4 2 Abdominal Pain/Discomfort Includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, and abdominal tenderness 2 2 Decline in Glomerular Filtration Rate (GFR) Decreased or abnormal GFR 2 2 Electrolyte Abnormalities Includes increased anion gap, decreased blood bicarbonate, hypomagnesemia, hyperosmolarity, hypokalemia, hyperkalemia, hypercalcemia, hypernatremia, hyperosmolar state, hyperuricemia, hypocalcemia, and hypophosphatemia 2 1 Fatigue 2 1 Headache 2 1 Abdominal Distension 1 1 Gastritis 1 1 Hiatus Hernia 1 0 Nasopharyngitis 1 1 * Reported in at least 1% of patients in either treatment group N = Total number of patients in the treatment group Table 2: Common Adverse Reactions* in Patients Undergoing Colonoscopy in the MORA Trial by Treatment Group Preferred Term PLENVU One-Day Morning Dosage Regimen (N = 271) % PLENVU Two-Day Split Dosage Regimen (N = 265) % 2 Liter PEG + Electrolytes Two-Day Split Dosage Regimen 2 Liter PEG Plus Electrolytes: Two doses each containing PEG 3350 100 grams, sodium sulfate 7.5 grams, sodium chloride 2.691 grams, potassium chloride 1.015 grams, sodium ascorbate 5.9 grams, and ascorbic acid 4.7 grams (N = 269) % Vomiting 7 4 1 Nausea 6 6 3 Dehydration Includes signs and symptoms of dehydration, including dizziness, dry mouth, orthostatic hypotension, pre-syncope, syncope, and thirst 4 3 2 Abdominal Pain/Discomfort Includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, and abdominal tenderness 3 2 3 Hypertension 2 1 0 Headache 1 2 2 Electrolyte Abnormalities Includes increased anion gap, decreased blood bicarbonate, hypomagnesemia, increased blood osmolarity, hypokalemia, hyperkalemia, hypercalcemia, hypernatremia, hyperosmolar state, hyperuricemia, hypocalcemia, and hypophosphatemia 1 1 0 * Reported in at least 1% of patients in either treatment group N = Total number of patients in the treatment group Electrolyte Changes Increases in serum sodium, chloride, calcium, magnesium, phosphate, and urate were noted in more patients treated with PLENVU compared with control in one or both trials.

The majority of these changes were transient and not clinically significant.

Associated decreases in bicarbonate and increases in serum osmolality were also noted.

Renal Function Decreases in creatinine clearance and increases in blood urea nitrogen (BUN) were also noted in more patients treated with PLENVU compared to control in both trials.

Changes of a magnitude indicative of possible acute renal injury, or worsening of baseline chronic renal impairment, were noted infrequently and occurred at a similar incidence in both PLENVU and comparator arms.

Adverse reactions in patients with mild renal impairment were similar to those in patients with normal renal function .

Less Common Adverse Reactions Less common adverse reactions (less than 1%) in the NOCT and MORA trials include: anorectal discomfort, hypersensitivity reaction (including rash), migraine, somnolence, asthenia, chills, pains, aches, palpitation, sinus tachycardia, hot flush, and transient increase in liver enzymes.

An additional 235 patients were exposed to the One-Day Morning Dosage Regimen of PLENVU in a third clinical trial, utilizing a comparator not approved in the United States.

The adverse reaction profile for patients receiving PLENVU in that trial was similar to what is described above.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of another oral formulation of polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride and potassium chloride or other polyethylene glycol (PEG)-based bowel preparations.

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.

Hypersensitivity: urticaria/rash, pruritus, dermatitis, rhinorrhea dyspnea, chest and throat tightness, fever, angioedema, anaphylaxis and anaphylactic shock [see Contraindications ( 4 )] Cardiovascular: arrhythmia, atrial fibrillation, peripheral edema, asystole, and acute pulmonary edema after aspiration Gastrointestinal: upper gastrointestinal bleeding from a Mallory-Weiss tear, esophageal perforation [usually with gastroesophageal reflux disease (GERD)] Nervous system: tremor, seizure