DailyMed Label: SUFLAVE

DailyMed Label: SUFLAVE

2023

DailyMed Prescription

SUFLAVE

polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride for oral solution

Braintree Laboratories, Inc.

NDC: 52268-550

NDC: 52268-550

NDC: 52268-550

NDC: 52268-550

SUFLAVE (polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride for oral solution) is an osmotic laxative and is provided in two bottles and two flavor enhancing packets for oral solution. The active ingredients contained in SUFLAVE are provided in Table 3. Table 3: Active Ingredients in SUFLAVE Chemical Name Chemical Formula Average Molecular Weight (g/mol) Chemical Structure Polyethlyene Glycol 3350, USP 3350 Sodium Sulfate, USP Na 2 SO 4 142.04 Magnesium Sulfate, USP MgSO 4 120.37 Potassium Chloride, USP KCl 74.55 Sodium Chloride, USP NaCl 58.44 Na + Cl - Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride, plus the following excipients: advantame, lemon-lime flavor, and neotame. Each flavor enhancing packet contains anhydrous citric acid, colloidal silicon dioxide, malic acid, and sucralose. Each dose of reconstituted oral solution is one liter of slightly hazy to hazy liquid that contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride and the following excipients: advantame, anhydrous citric acid, colloidal silicon dioxide, lemon-lime flavor, malic acid, neotame, and sucralose. PEG3350 PEG3350 Sodium Sulfate Magnesium Sulfate Potassium Chloride

SUFLAVE is indicated for the cleansing of the colon as a preparation for colonoscopy in adults. SUFLAVE is an osmotic laxative indicated for cleansing of the colon in preparation for colonoscopy in adults.

Preparation and Administration ( 2.1 ) Administration of two doses of SUFLAVE are required for a complete preparation for colonoscopy.  One dose of SUFLAVE is equal to one bottle plus one flavor enhancing packet. Each bottle must be reconstituted with water before ingestion. An additional 16 ounces of water must be consumed after each dose. Stop consumption of all fluids at least 2 hours before the colonoscopy. Recommended Dosage and Administration ( 2.2 ) The recommended Split-Dose (two-day) regimen consists of two doses of SUFLAVE : o Day 1,  Dose 1: Evening before Colonoscopy:  1 bottle with flavor enhancing packet o Day 2,  Dose 2: Morning of the Colonoscopy (5 to 8 hours prior to the colonoscopy and no sooner than 4 hours from starting Dose 1): 1 bottle with flavor enhancing packet For complete information on preparation before colonoscopy and administration of the dosage regimen, see full prescribing information. ( 2.1 , 2.2 ) Correct fluid and electrolyte abnormalities before treatment with SUFLAVE [see Warnings and Precautions ( 5.1 )] Two doses of SUFLAVE are required for a complete preparation for colonoscopy. One dose of SUFLAVE is equal to one bottle plus one flavor enhancing packet. Reconstitue each bottle with water before ingestion. Do not reconstitute SUFLAVE with liquids other than water and/or add starch-based thickeners to the mixing bottle  [see Warnings and Precautions ( 5.7 )] . Must consume an additional 16 ounces of water after each dose of SUFLAVE. Consume a low residue breakfast on the day before colonoscopy. After breakfast, only consume clear liquids up to 2 hours prior to colonoscopy. Do not eat solid food or drink milk or eat or drink anything colored red or purple. Do not drink alcohol. Do not take other laxatives while taking SUFLAVE.  [see Drug Interactions ( 7.3 )]. Do not take oral medications within 1 hour of starting each dose of SUFLAVE.  [see Drug Interactions ( 7.2 )]. 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 SUFLAVE [see Drug Interactions ( 7.2 )] . Stop consumption of all fluids at least 2 hours prior to the colonoscopy. If nausea, bloating, or abdominal cramping occurs, pause or slow the rate of drinking the solution and additional water until symptoms diminish. The recommended Split-Dose (two-day) regimen consists of two doses of SUFLAVE: Day 1, Dose 1: Evening before Colonoscopy : 1 bottle with flavor enhancing packet Day 2, Dose 2: Morning of the Colonoscopy (5 to 8 hours prior to the colonoscopy and no sooner than 4 hours from starting Dose 1) : 1 bottle with flavor enhancing packet The Day Prior to Colonoscopy: A low residue breakfast may be consumed. Examples of low residue foods are white bread, biscuits, muffins (no wheat), cornflakes, eggs, cream of wheat, grits, yogurt, cottage cheese, coffee, tea, juice without pulp, fruit (no skin or seeds). After breakfast, only consume clear liquids until after the colonoscopy. Examples of clear liquids are water, fruit juice (without pulp), lemonade, plain coffee, tea (no cream or non-dairy creamer), chicken broth, gelatin dessert (no fruit or topping). No red or purple liquids, no milk or alcoholic beverages. Day 1, Dose 1 - Early in the Evening Prior to Colonoscopy: Open 1 flavor enhancing packet and pour the contents into 1 bottle. Fill the provided bottle with lukewarm water up to the fill line. After capping the bottle, gently shake the bottle until all powder has dissolved. For best taste, refrigerate the solution for an hour before drinking. Do not freeze. Use within 24 hours. Drink 8 ounces of solution every 15 minutes until the bottle is empty. Drink an additional 16 ounces of water during the evening. If nausea, bloating, or abdominal cramping occurs, pause or slow the rate of drinking the solution and additional water until symptoms diminish. Day 2, Dose 2 - The Morning of the Colonoscopy (5 to 8 hours prior to the colonoscopy and no sooner than 4 hours from starting Dose 1): Continue to consume only clear liquids until after the colonoscopy. Repeat Step 1 to Step 3 from Day 1, Dose 1. Drink an additional 16 ounces of water during the morning. Stop drinking liquids at least 2 hours prior to colonoscopy. If nausea, bloating, or abdominal cramping occurs, pause or slow the rate of drinking the solution and additional water until symptoms diminish. Storage of Reconstituted Solution After reconstitution, keep solution refrigerated 2°C to 8°C (36°F to 46°F). Do not freeze. Use within 24 hours, discard unused solution.

SUFLAVE is supplied as a white powder for reconstitution and is available in a carton that contains two bottles and two flavor enhancing packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. The bottle contains lemon-lime flavoring. When diluted as directed, the solution is slightly hazy to hazy. For Oral Solution: Two bottles and two flavor enhancing packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. The bottle also contains lemon-lime flavoring. ( 3 )

SUFLAVE is contraindicated in the following conditions: Gastrointestinal obstruction or ileus [see Warnings and Precautions ( 5.6 )] Bowel perforation [see Warnings and Precautions ( 5.6 )] Toxic colitis or toxic megacolon Gastric retention Hypersensitivity to any ingredient in SUFLAVE  [see Warnings and Precautions ( 5.8 )] Gastrointestinal obstruction or ileus ( 4 , 5.6 ) Bowel perforation ( 4 , 5.6 ) Toxic colitis or toxic megacolon ( 4 ) Gastric retention ( 4 ) Hypersensitivity to any ingredient in SUFLAVE ( 4 )

Risk of fluid and electrolyte abnormalities : Encourage adequate hydration, assess concurrent medications and consider laboratory assessments prior to and after each use. ( 5.1 , 7.1 ) Cardiac arrhythmias : Consider pre-dose and post-colonoscopy ECGs in patients at increased risk. ( 5.2 ) Seizures : Use caution in patients with a history of seizures and patients at increased risk of seizures, including medications that lower the seizure threshold. ( 5.3 , 7.1 ) Colonic mucosal ulcerations : Consider potential for ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. ( 5.5 ) Patients with renal impairment or taking concomitant medications that affect renal function : Use caution, ensure adequate hydration and consider laboratory testing. ( 5.4 , 7.1 ) Suspected GI obstruction or perforation : Rule out the diagnosis before administration. ( 4 , 5.6 ) Patients at risk for aspiration : Observe during administration ( 5.7 ) Hypersensitivity reactions, including anaphylaxis : Inform patients to seek immediate medical care if symptoms occur ( 5.8 ) Advise all patients to hydrate adequately before, during, and after the use of SUFLAVE. If a patient develops significant vomiting or signs of dehydration after taking SUFLAVE, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN). Bowel preparation products can cause fluid and electrolyte disturbances, which can lead to serious adverse reactions including cardiac arrhythmias, seizures, and renal impairment [see Adverse Reactions ( 6.2 )] . Correct fluid and electrolyte abnormalities before treatment with SUFLAVE. Use SUFLAVE with caution in patients with conditions, or who are using medications [such as diuretics, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)], that increase the risk for fluid and electrolyte disturbances or may increase the risk of seizure, arrhythmias, and renal impairment [see Drug Interactions ( 7.1 )] . There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. These occur predominantly in patients with underlying cardiac risk factors and electrolyte disturbances. Use caution when prescribing SUFLAVE for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT interval, 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. 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 SUFLAVE 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 )] . Use SUFLAVE 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 SUFLAVE and consider performing baseline and postcolonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Use in Specific  Populations ( 8.6 )] . Osmotic laxative products may produce colonic mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of stimulant laxatives and SUFLAVE 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. If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering SUFLAVE [see Contraindications ( 4 )] . Use with caution in patients with severe active ulcerative colitis. Patients with impaired gag reflex or other swallowing abnormalities are at risk for regurgitation or aspiration of SUFLAVE. Observe these patients during administration of SUFLAVE. Do not combine SUFLAVE with starch-based thickeners [see Dosage and Administration ( 2.1 )] . Polyethylene glycol (PEG), a component of SUFLAVE, when mixed with starch-thickened liquids reduces the viscosity of the starch-thickened liquid. When a PEG-based product used for another indication was mixed in starch-based pre-thickened liquids used in patients with dysphagia, thinning of the liquid occurred and cases of choking and potential aspiration were reported. SUFLAVE contains polyethylene glycol (PEG) and other ingredients that may cause serious hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and pruritus [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.

The following serious or otherwise important adverse reactions for bowel preparations are described elsewhere in the labeling:

Drugs that increase risk of fluid and electrolyte imbalance. ( 7.1 ) Use caution when prescribing SUFLAVE to patients taking medications that increase the risk of fluid and electrolyte disturbances or may increase the risk of adverse events of seizure, arrhythmias, and prolonged QT in the setting of fluid and electrolyte abnormalities [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 )] . SUFLAVE can reduce the absorption of other co-administered drugs [see Dosage and Administration ( 2.1 )] : Administer oral medications at least one hour before starting each dose of SUFLAVE. Administer tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, and penicillamine at least 2 hours before and not less than 6 hours after administration of each dose of SUFLAVE to avoid chelation with magnesium. Concurrent use of stimulant laxatives and SUFLAVE may increase the risk of mucosal ulceration or ischemic colitis. Avoid use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) while taking SUFLAVE [see Warnings and Precautions ( 5.5 )] .

Risk Summary There are no available data on the use of SUFLAVE during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride (SUFLAVE). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Risk Summary There are no available data on the presence of SUFLAVE in human or animal milk, the effects of on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SUFLAVE and any potential adverse effects on the breastfed child from SUFLAVE or from the underlying maternal condition. The safety and effectiveness of SUFLAVE in pediatric patients have not been established. Of the 460 patients who received SUFLAVE in clinical trials, 125 (27%) were 65 years of age or older. No differences in effectiveness of SUFLAVE were observed between geriatric patients and younger adult patients. Among geriatric patients, decreases in blood pressure on the day of colonoscopy were reported more frequently with SUFLAVE than with the active comparator in Study 1 (6% in SUFLAVE-treated patients and 1% in patients treated with active comparator) in Study 2 (3% in SUFLAVE-treated patients and 0% treated with active comparator) [see Clinical Studies ( 14 )] . Geriatric 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 )] . Advise geriatric patients to hydrate adequately before, during, and after the use of SUFLAVE. Use SUFLAVE 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 SUFLAVE and consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients [see Warning and Precautions ( 5.4 )] .

SUFLAVE (polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride for oral solution) is supplied as a white powder for reconstitution and is lemon-lime flavored. Each carton of SUFLAVE (NDC 52268-550-01) contains: Two bottles, each bottle (NDC 52268-551-01), closed with child resistant closure, contains a white powder of 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride for reconstitution. The bottle contains lemon-lime flavor. Two flavor enhancing packets (NDC 52268-552-01). Storage Store SUFLAVE at room temperature between 20º to 25°C (68º to 77°F), excursions permitted from 15º to 30°C (59º to 86°F). See USP controlled room temperature.

The primary mode of action is the osmotic effects of polyethylene glycol 3350, sodium sulfate and magnesium sulfate, which induce a laxative effect. The physiological consequence is increased water retention in the lumen of the colon, resulting in loose stools. After administration of the first dose of SUFLAVE in 18 healthy subjects, the mean ± SD maximum plasma concentration (C max ) for polyethylene glycol 3350 of 3.4 ± 1.4 mcg/mL was reached at 4 hours, and the mean ± SD serum C max for sulfate of 27.0 ± 11.4 mcg/mL was reached at 6 hours. Following a second dose of SUFLAVE (approximately 12 hours later), the mean ± SD plasma C max for polyethylene glycol 3350 of 2.9 ± 0.97 mcg/mL was reached at 4 hours, and the mean ± SD serum C max for sulfate of 29.2 ± 11.0 mcg/mL was reached at 3 hours. Sulfate concentrations were below the limit of quantitation (19.2 mcg/mL) for all subjects by follow-up Day 3. Polyethylene glycol 3350 concentrations were below the limit of quantitation (LOQ 0.01 mcg/mL) for 16 of 18 subjects by follow-up Day 7.

The colon cleansing efficacy of SUFLAVE was evaluated in two randomized, single-blind, active-controlled, multicenter trials (Study 1 and Study 2). These trials included adult patients undergoing colonoscopy for colorectal cancer screening and surveillance, or diagnostic colonoscopy, including patients with abdominal pain, diarrhea, constipation and non-severe inflammatory bowel disease. In Study 1 ( NCT04446299 ), 471 adult patients were included in the efficacy analysis. Patients ranged in age from 20 to 84 years (median age 58 years) and 54% were female. The racial distribution was 70% White, 27% African-American, 2% Asian, and 1% American Indian or Alaska Native. The population was 8% Hispanic or Latino. Patients were randomized to one of the following two colon preparation regimens: SUFLAVE or polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, ascorbic acid and sodium ascorbate for oral solution. Both preparations were administered according to a split-dose regimen [see Dosage and Administration ( 2.2 )] . Patients receiving SUFLAVE were limited to a low residue breakfast followed by clear liquids on the day prior to the 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 on the day prior to the colonoscopy. In Study 2 ( NCT04446312 ), 450 adult patients were included in the efficacy analysis. Patients ranged in age from 18 to 80 years (median age 57 years) and 58% were female. The racial distribution was 85% White, 10% African-American, 3% Asian, and < 1% American Indian or Alaska Native. The population was 21% Hispanic or Latino. Patients were randomized to one of the following two colon preparation regimens: SUFLAVE or sodium sulfate, potassium sulfate, and magnesium sulfate oral solution. Both preparations were administered according to a split-dose regimen [see Dosage and Administration ( 2.2 )] . Patients receiving SUFLAVE were limited to a low residue breakfast followed by clear liquids on the day prior to the colonoscopy; patients receiving the comparator bowel prep were allowed a light breakfast followed by clear liquids on the day prior to the colonoscopy. 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 scale described in Table 4. Success was defined as an overall cleansing assessment of 3 (Good) or 4 (Excellent). Table 4: Description of Colonoscopy Scoring  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 5. In both trials, SUFLAVE was non-inferior to the active comparator. Table 5: 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, with scores assigned on withdrawal of colonoscope. b  common risk differences and confidence intervals were based on Mantel-Haenszel method adjusting for study site c  active comparator in Study 1 was polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution d  active comparator in Study 2 was sodium sulfate, potassium sulfate, and magnesium sulfate oral solution e non-inferiority was demonstrated SUFLAVE % (n/N) Active Comparator % (n/N) SUFLAVE-Active Comparator Difference b (%) 99% Confidence Interval b Study 1 93% (215/232) 89% c (212/239) 3.4% (-1.7%, 8.5%) e Study 2 94% (212/226) 94% d (211/224) 0.2% (-4.0%, 4.3%) e

Principal Display Panel - Carton Label NDC 52268-550-01 Dispense the enclosed Medication Guide to each patient. SUFLAVE (polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride for oral solution) 178.7g/7.3g/1.12 g/0.9g/0.5g 2 Doses of SUFLAVE are required for a complete preparation. This carton contains: 2 Flavor Enhancing Packets 2 Bottles 1 Patient booklet, which includes: 1. Instructions for Use 2. Full Prescribing Information 3. Medication Guide © 2023 Braintree Labroatories, Inc. All rights reserved. 6/2023 Rx only Braintree A PART OF SEBELA PHARMACEUTICALS® SUFLAVE Carton PDP