Peg-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate And Ascorbic Acid

1 INDICATIONS AND USAGE PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults

2 DOSAGE AND ADMINISTRATION Preparation and Administration: Two doses of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution are required for a complete preparation for colonoscopy, using a "Two-Day" preferred method or "One-Day" alternative method dosing regimen. ( 2.1 ) PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution must be reconstituted in water prior to ingestion. ( 2.1 ) Additional clear liquids must be consumed after each dose of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution in both dosing regiments. ( 2.1 , 5.1 ) Do not take other laxatives while taking PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution. ( 2.1 , 5.5 ) Do not take oral medications within 1 hour of starting each dose. ( 2.1 ) Dosing Regimen: Two-Day (Split-Dose) (Preferred Method) : Dose 1 the evening before the colonoscopy, and Dose 2 the morning of the colonoscopy (approximately 12 hours after the start of Dose 1, and at least 3 ½ hours prior to the colonoscopy). ( 2.2 ) One-Day (Evening Only) (Alternative Method) : Dose 1 at least 3 ½ hours prior to bedtime the evening before the colonoscopy and Dose 2 approximately 1 ½ hours after starting Dose 1 the evening before the colonoscopy. ( 2.3 ) For complete information on dosing, preparation and administration see full prescribing information ( 2.1 , 2.2 , 2.3 ) 2.1 Important Preparation and Administration Instructions Correct fluid and electrolyte abnormalities before treatment with PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution [ see Warnings and Precautions (5.1) ]. Two doses of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution are required for a complete preparation for colonoscopy. The time interval between the two doses depends on the regimen prescribed and the planned timing of the colonoscopy procedure. [see Dosage and Administration ( 2.2 , 2.3 ) ] . The "Split-Dose" is the preferred method and consists of two separate doses: the first dose is taken the evening before the colonoscopy, and the second dose is taken the next day, the morning of the day of the colonoscopy [ see Dosage and Administration (2.2) ]. The "Evening Only" is the alternative method and consists of two separate doses: both doses are taken in the evening before the day of the colonoscopy, with a minimum of 1.5 hours between the start of the first dose and the start of the second dose [ see Dosage and Administration (2.3) ]. Both PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution dosing regimens require administration of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution using the mixing container provided to reconstitute the contents of Pouch A, Pouch B and Lemon flavor pack with water to the Fill Line. Do not reconstitute with other liquids and/or add starch-based thickeners to the mixing container [see Warnings and Precautions (5.7) ]. Additional clear liquids (including water) must be consumed in both dosing regimens [see Dosage and Administration ( 2.2 , 2.3 ), Warnings and Precautions (5.1) ] . Consume only clear liquids (no solid food) from the start of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution treatment until after the colonoscopy. Do not eat or drink alcohol, milk, anything colored red or purple or any other foods containing pulp material. Do not take other laxatives while taking PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution [ see Drug Interactions (7.3) ] . Do not take oral medications within 1 hour before or after starting each dose of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution [ see Drug Interactions (7.2) ]. Ensure completion of Dose 2, including all additional liquids, at least 2 hours before the colonoscopy. Storage : After reconstitution, store PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution- solution in an upright position and keep refrigerated. Use within 24 hours after it is mixed in water. 2.2 Two-Day Split-Dosing Regimen (Preferred Method) The Two-Day Split-Dosing regimen is the preferred dosing method. Instruct adult patients that on the day before the clinical procedure, they can consume breakfast, followed by a light lunch (no solid foods), and clear soup and/or plain yogurt for dinner, which must be completed at least 1 hour prior to the start of the first PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution dose. Instruct adult patients to take two separate doses in conjunction with fluids as follows: Dose 1 – In the evening before the colonoscopy, approximately 10 to 12 hours before Dose 2: Empty the contents of 1 Pouch A, 1 Pouch B and 1 Lemon Flavor pack into the mixing container that comes with PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution- solution. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A, Pouch B and Lemon flavor pack are completely dissolved. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all the solution. Refill the mixing container halfway to the Fill Line (at least 16 ounces) with a clear liquid and drink all this liquid before going to bed. Dose 2 – Take next morning, on the day of the colonoscopy, approximately 12 hours after the start of Dose 1 and at least 3 ½ hours prior to colonoscopy: Empty the contents of 1 Pouch A, 1 Pouch B and 1 Lemon flavor pack into the mixing container that comes with PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution- solution. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A, Pouch B and Lemon flavor pack are completely dissolved. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all of the solution. Refill the mixing container halfway to the Fill Line (at least 16 ounces) with a clear liquid and drink all this liquid at least 2 hours before the colonoscopy. Consume additional water or clear liquids up to 2 hours before the colonoscopy or as prescribed by your healthcare provider. Then stop drinking liquids until after the colonoscopy. Stop drinking PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution temporarily or drink each portion at longer intervals if severe bloating, abdominal discomfort or distention occurs, until these symptoms resolve. 2.3 One-Day Evening Only Dosing Regimen (Alternative Method) The One-Day Evening Only regimen is the alternative dosing method for patients for whom the Split-Dosing regimen is inappropriate. Instruct adult patients that on the day before the clinical procedure, they can consume breakfast, followed by a light lunch (no solid foods), and clear soup and/or plain yogurt for dinner, which must be completed at least 1 hour prior to the start of the first PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution dose. Instruct adult patients to take two separate doses in conjunction with fluids as follows: Dose 1 – At least 3 ½ hours before bedtime the evening before the colonoscopy : Empty the contents of 1 Pouch A, 1 Pouch B and 1 Lemon Flavor pack into the mixing container that comes with PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution- solution. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A, Pouch B and Lemon Flavor pack are completely dissolved. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all the solution. Dose 2 – At least 1 ½ hours after starting Dose 1 on the evening before the colonoscopy : Empty the contents of 1 Pouch A, 1 Pouch B and 1 Lemon Flavor pack into the mixing container that comes with PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution. Add lukewarm water to the Fill Line on the mixing container (32 fluid ounces). Do not add other ingredients to the PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution- solution. Thoroughly mix with a spoon or shake with lid on securely until the contents of Pouch A, Pouch B and Lemon Flavor pack are completely dissolved. Drink 8 ounces of the solution every 15 minutes. This should take about 1 hour. Be sure to drink all of the solution. Refill the mixing container to the Fill Line (32 fluid ounces) with a clear liquid and drink all this liquid before going to bed. Consume additional water or clear liquids up to 2 hours before the colonoscopy or as prescribed by your healthcare provider. Then stop drinking liquids until after the colonoscopy. Stop drinking PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution temporarily or drink each portion at longer intervals if severe bloating, abdominal discomfort or distention occurs, until these symptoms resolve.

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) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.10) ] Most common adverse reactions (≥ 5%) are: Two-Day (Split-Dose): malaise, nausea, abdominal pain, vomiting, and upper abdominal pain. ( 6.1 ) One-Day (Evening-Only): abdominal distension, anal discomfort, thirst, nausea, abdominal pain, sleep disorder, rigors, hunger, malaise, vomiting, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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 clinical practice. The safety of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution as a Two-Day Split-Dosing and One-Day Evening Only Dosing Regimen was evaluated in two randomized, active-controlled, multicenter, investigator-blinded clinical trials in adult patients scheduled to have an elective colonoscopy [see Clinical Studies (14)] . The safety analysis for Study 1 included 359 adult patients ranging in age from 18 to 88 years (mean age 59), with 52% female and 48% male patients. The safety analysis for Study 2 included 340 adult patients ranging in age from 21 to 76 years (mean age 53), with 53% male and 47% female patients. Tables 1 and 2 display adverse reactions reported in at least 2% and 5% of patients in either treatment group in Study 1 and Study 2, 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 Reactions1 in Patients Undergoing Colonoscopy in Study 11 PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution Two-Day Split Dosing Regimen (N=180) 4 Liter PEG + Electrolytes Solution (N=179) Malaise 19% 18% Nausea 14% 20% Abdominal pain 13% 15% Vomiting 8% 13% Upper abdominal pain 6% 6% Dyspepsia 3% 1% 1 Reported in at least 2% of patients in either treatment group Table 2: Common Adverse Reactions1,2 in Patients Undergoing Colonoscopy in Study 22 PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution One-Day Evening Only Dosing Regimen(N=169) 90 mL Oral Sodium Phosphate Solution (N=171) Abdominal distension 60% 41% Anal discomfort 51% 52% Thirst 47% 65% Nausea 47% 47% Abdominal pain 39% 32% Sleep disorder 35% 29% Rigors 34% 30% Hunger 30% 71% Malaise 27% 53% Vomiting 7% 8% Dizziness 7% 18% Headache 2% 5% Hypokalemia 0% 6% Hyperphosphatemia 0% 6% 1 Reported in at least 5% of patients in either treatment group 2 Patients were specifically asked about the occurrence of the following symptoms: shivering, anal irritations, abdominal bloating or fullness, sleep loss, nausea, vomiting, weakness, hunger sensation, abdominal cramps or pain, thirst sensation, and dizziness. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of PEG-3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate, and Ascorbic Acid for Oral Solution or other PEG-based products. 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. Cardiovascular: Tachycardia, palpitations, hypertension, arrhythmia, atrial fibrillation, peripheral edema, asystole, acute pulmonary edema and syncope, and dehydration. Gastrointestinal: upper gastrointestinal bleeding from a Mallory-Weiss tear, esophageal perforation [usually with gastroesophageal reflux disease (GERD)] Hypersensitivity reactions: anaphylaxis (some of which were severe, including shock), rash, urticaria, pruritus, lip, tongue and facial swelling, dyspnea, chest tightness and throat tightness, rhinorrhea, dermatitis, fever, and chills [see Warnings and Precautions (5.10) ]. Nervous system: tremor, seizure. Renal: renal impairment and/or failure.