asic sodium phosphate and dibasic sodium phosphate tablets dose [see dosage and administration (2.1) ] . 7.3 other sodium phosphate-based laxatives administration of additional sodium phosphate-based purgative or enema products with monobasic sodium phosphate and dibasic sodium phosphate tablets may increase the risk of acute phosphate nephropathy. avoid concomitant use [see warnings and precautions (5.1) ] .

sensitivity reactions, including anaphylaxis : inform patients to seek immediate medical care if symptoms occur. ( 5.7 ) 5.1 renal disease, acute phosphate nephropathy, and electrolyte disorders renal disease and acute phosphate nephropathy there have been rare, but serious, reports of renal failure, acute phosphate nephropathy, and nephrocalcinosis in patients who received oral sodium phosphate products, including monobasic sodium phosphate and dibasic sodium phosphate tablets, for colon cleansing prior to colonoscopy. these cases often resulted in permanent impairment of renal function and several patients required long-term dialysis. the time to onset is typically within days; however, in some cases, the diagnosis of these events has been delayed up to several months after the ingestion of these products. patients at increased risk of acute phosphate nephropathy may include patients with the following: hypovolemia, baseline kidney disease, increased age, and patients using medicines that affect renal perfusion or function [such as diuretics, angiotensin-converting enzyme (ace) inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs (nsaids) [see drug interactions (7.1) ] . electrolyte disorders bowel preparations, including monobasic sodium phosphate and dibasic sodium phosphate tabletscan cause fluid and electrolyte disturbances, which can lead to serious adverse reactions including cardiac arrhythmias, seizures and renal impairment [see adverse reactions (6.2) ] . patient management monobasic sodium phosphate and dibasic sodium phosphate tablets are contraindicated in patients with a history of acute phosphate nephropathy [see contraindications (4) ]. use monobasic sodium phosphate and dibasic sodium phosphate tablets with caution in patients with severe renal impairment (creatinine clearance less than 30 ml/minute), with conditions, or who are taking medications, that increase the risk for fluid and electrolyte disturbances or may increase the risk of arrhythmias, seizures, or renal impairment. consider performing baseline and post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and bun) in these patients [see drug interactions (7.1) ] . correct electrolyte abnormalities such as hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia before treatment with monobasic sodium phosphate and dibasic sodium phosphate tablets [see dosage and administration (2.1) ] . avoid additional sodium phosphate-based purgative or enema products [see drug interactions (7.1) ] . advise all patients to hydrate adequately before, during, and after the use of monobasic sodium phosphate and dibasic sodium phosphate tablets [see dosage and administration (2.1,2.2) ] . if a patient develops significant vomiting or signs of dehydration while or after taking monobasic sodium phosphate and dibasic sodium phosphate tablets, consider performing post-colonoscopy lab tests [electrolytes, creatinine, and blood urea nitrogen (bun)]. 5.2 cardiac arrhythmias there have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. qt prolongation with sodium phosphate tablets has been associated with electrolyte imbalances, such as hypokalemia and hypocalcemia. use caution when prescribing monobasic sodium phosphate and dibasic sodium phosphate tablets for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged qt, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy) and those taking medications known to prolong the qt interval, since serious complications may occur. consider pre-dose and post-colonoscopy ecgs in patients at increased risk of serious cardiac arrhythmias. 5.3 seizures there have been rare reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of sodium phosphate osmotic laxative products, such as monobasic sodium phosphate and dibasic sodium phosphate tablets, 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 monobasic sodium phosphate and dibasic sodium phosphate tablets with caution in patients with a history of seizures and in patients at higher risk of seizure, such as patients taking medications that lower the seizure threshold (such as tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, or patients with known or suspected hyponatremia [see drug interactions (7.1) ] . 5.4 use in patients with significant gastrointestinal disease if gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering monobasic sodium phosphate and dibasic sodium phosphate tablets [see contraindications (4) ] . use with caution in patients with severe active ulcerative colitis. 5.5 colonic mucosal ulceration and inflammatory bowel disease osmotic laxatives, including monobasic sodium phosphate and dibasic sodium phosphate tablets, may induce colonic mucosal aphthous ulcerations. in the monobasic sodium phosphate and dibasic sodium phosphate tablets clinical program, aphthous ulcers were observed in 3% of patients who took the recommended monobasic sodium phosphate and dibasic sodium phosphate tablets dosing regimen. consider the potential for mucosal ulcerations resulting from bowel preparation when interpreting colonoscopic finding should in patients with known or suspected inflammatory bowel disease. use monobasic sodium phosphate and dibasic sodium phosphate tablets with caution in patients experiencing an acute exacerbation of chronic inflammatory bowel disease as published data suggest that sodium phosphate absorption may be enhanced in such patients. 5.6 aspiration patients with impaired gag reflex or other swallowing abnormalities are at risk for regurgitation or aspiration of monobasic sodium phosphate and dibasic sodium phosphate tablets. observed these patients during administration of monobasic sodium phosphate and dibasic sodium phosphate tablets. 5.7 hypersensitivity reactions monobasic sodium phosphate and dibasic sodium phosphate tablets may cause serious hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and throat tightness [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.

ic sodium phosphate and dibasic sodium phosphate tablets [ see warnings and precautions (5.1) ] . clear liquids must be consumed before, during and after taking monobasic sodium phosphate and dibasic sodium phosphate tablets [see dosage and administration (2.1) , warnings and precautions (5.1) ] . do not administer monobasic sodium phosphate and dibasic sodium phosphate tablets within 7 days of a previous use. two doses of monobasic sodium phosphate and dibasic sodium phosphate tablets are required for a complete preparation for colonoscopy: the first dose the evening before the colonoscopy and the second dose on the morning of the colonoscopy [see dosage and administration (2.2) ]. consume only clear liquids (no solid food) from the start of monobasic sodium phosphate and dibasic sodium phosphate tablets 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 monobasic sodium phosphate and dibasic sodium phosphate tablets, particularly additional sodium phosphate-based purgative or enema products [see drug interactions (7.3) ] . do not take oral medications within 1 hour before or after starting each dose of monobasic sodium phosphate and dibasic sodium phosphate tablets [see drug interactions (7.2) ] . 2.2 dosage regimen instruct adult patients that on the day before their colonoscopy, they can consume a light breakfast consisting of clear soup and/or plain yogurt (no solid foods) before noon, followed by only clear liquids until after the colonoscopy. the recommended dose of monobasic sodium phosphate and dibasic sodium phosphate tablets for colon cleansing for adult patients is 32 tablets (48 grams of sodium phosphate) taken orally with a total of 2 quarts of clear liquids in the following manner: the evening before the colonoscopy : take 4 monobasic sodium phosphate and dibasic sodium phosphate tablets with 8 ounces of clear liquids every 15 minutes for a total of 20 tablets. on the day of the colonoscopy starting 3 to 5 hours before the procedure : take 4 monobasic sodium phosphate and dibasic sodium phosphate tablets with 8 ounces of clear liquids every 15 minutes for a total of 12 tablets.

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 monobasic sodium phosphate and dibasic sodium phosphate tablets was evaluated in two randomized, investigator-blinded, active controlled trials in 931 adult patients undergoing elective colonoscopy. the mean age of the study population was 60 years (range 20 to 89 years), 88% of patients were caucasian and 55% were female [see clinical studies (14) ] . table 1 shows the most common adverse reactions reported in greater than 3% of patients by treatment group in study 1 [see clinical studies (14) ]. since diarrhea was considered as a part of the efficacy of monobasic sodium phosphate and dibasic sodium phosphate tablets, diarrhea was not defined as an adverse event in this clinical trial. 1 reported in more than 3% of patients in at least one treatment group 2 another oral formulation of monobasic sodium phosphate and dibasic sodium phosphate table 1: common adverse reactions 1 in patients undergoing colonoscopy in study 1 monobasic sodium phosphate and dibasic sodium phosphate tablets 32 tabs (48 g) n=272 monobasic sodium phosphate and dibasic sodium phosphate tablets 40 tabs (60 g) n=265 sodium phosphate2 40 tabs (60 g) n=268 bloating 31% 39% 41% nausea 26% 37% 30% abdominal pain 23% 24% 25% vomiting 4% 10% 9% electrolyte abnormalities in study 1 hyperphosphatemia a total of, 96%, 96%, and 93% of patients who took 60 grams of oral sodium phosphate, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, respectively, developed hyperphosphatemia (defined as phosphate level > 5.1 mg/dl) on the day of the colonoscopy. in this study, patients who took 60 grams of oral sodium phosphate, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets had baseline mean phosphate levels of 3.5, 3.5, and 3.6 mg/dl and subsequently developed mean phosphate levels of 7.6, 7.9, and 7.1 mg/dl, respectively, on the day of the colonoscopy. hyperkalemia a total of 20%, 22%, and 18% of patients who took 60 grams of oral sodium phosphate, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, respectively, developed hypokalemia (defined as a potassium level < 3.4 meq/l) on the day of the colonoscopy. in this study, patients who took 60 grams of oral sodium phosphate, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets all had baseline potassium levels of about 4.3 meq/l and then developed a mean potassium level of 3.7 meq/l on the day of the colonoscopy. several patients on all three sodium phosphate regimens developed hypocalcemia and hypernatremia that did not require treatment. the monobasic sodium phosphate and dibasic sodium phosphate tablets 60-gram dosage regimen was associated with an increased risk of adverse reactions compared to the 48- gram dosage regimen and a similar overall response rate [see clinical studies (14) ] . therefore, the monobasic sodium phosphate and dibasic sodium phosphate tablets 60-gram dosage is not a recommended regimen [see dosage and administration (2.2) ]. 6.2 postmarketing experience the following adverse reactions have been identified during post-approval use of monobasic sodium phosphate and dibasic sodium phosphate tablets. because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. hypersensitivity reactions : anaphylaxis, angioedema (swelling of the lips, tongue and face), rash, pruritus, urticaria, throat tightness, bronchospasm, dyspnea, pharyngeal edema, dysphagia, and paresthesia. cardiovascular: arrhythmias nervous system: seizures renal: renal impairment, increased blood urea nitrogen (bun), increased creatinine, acute renal failure, acute phosphate nephropathy, nephrocalcinosis, and renal tubular necrosis.

asic sodium phosphate and dibasic sodium phosphate tablets dose [see dosage and administration (2.1) ] . 7.3 other sodium phosphate-based laxatives administration of additional sodium phosphate-based purgative or enema products with monobasic sodium phosphate and dibasic sodium phosphate tablets may increase the risk of acute phosphate nephropathy. avoid concomitant use [see warnings and precautions (5.1) ] .

hate tablets to a child during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for monobasic sodium phosphate and dibasic sodium phosphate tablets and any potential adverse effects on the breastfed child from monobasic sodium phosphate and dibasic sodium phosphate tablets or from the underlying maternal condition. 8.4 pediatric use safety and effectiveness in pediatric patients have not been established. 8.5 geriatric use of the 599 patients in clinical trials receiving at least 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, 134 (22%) were 65 years of age or older, while 27 (5%) were 75 years of age or older. no overall differences in safety or effectiveness were observed between geriatric patients and younger patients. however, the mean phosphate levels in geriatric patients were greater than the phosphate levels in younger patients after monobasic sodium phosphate and dibasic sodium phosphate tablets administration. the mean colonoscopy-day phosphate levels in patients 18-64, 65-74, and ≥ 75 years old who received the recommended monobasic sodium phosphate and dibasic sodium phosphate tablets dosage regimen in study 1were 7.0, 7.3, and 8.0 mg/dl, respectively. after monobasic sodium phosphate and dibasic sodium phosphate tablets administration, the mean phosphate levels in patients 18-64, 65-74, and ≥ 75 years old were 7.4, 7.9, and 8.0 mg/dl, respectively. greater sensitivity of some older individuals cannot be ruled out; therefore, use monobasic sodium phosphate and dibasic sodium phosphate tablets with caution in geriatric patients. advise geriatric patients to adequately hydrate before, during, and after the use of monobasic sodium phosphate and dibasic sodium phosphate tablets. sodium phosphate is known to be substantially excreted by the kidney, and the risk of adverse reactions with sodium phosphate may be greater in patients with impaired renal function. since geriatric patients are more likely to have impaired renal function, consider performing baseline and post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and bun) in these patients [see warnings and precautions (5.1) ]. 8.6 renal impairment sodium phosphate is substantially excreted by the kidney. use monobasic sodium phosphate and dibasic sodium phosphate tablets with caution in patients with severe renal impairment (creatinine clearance less than 30 ml/min) 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 the use of monobasic sodium phosphate and dibasic sodium phosphate tablets, and consider performing baseline and post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and bun) in these patients [see warnings and precautions (5.1) , drug interactions (7.1) ] .

hy subjects was performed to determine the concentration-time profile of serum inorganic phosphorus levels after oral sodium phosphate administration. all subjects received the approved dosing regimen for colon cleansing of 60 grams of sodium phosphate with a total liquid volume of 3.6 quarts. a 30-gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) was given beginning at 6 pm in the evening. the 30-gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) was repeated the following morning beginning at 6 am. twenty-three healthy subjects (mean age 57 years old; 57% male and 43% female; and 65% hispanic, 30% caucasian, and 4% african-american) participated in this pharmacokinetic study. the serum phosphorus level rose from a mean (± standard deviation) baseline of 4.0 (± 0.7) mg/dl to 7.7 (± 1.6 mg/dl), at a median of 3 hours after the administration of the first 30-gram dose of sodium phosphate tablets (see figure 1 ). the serum phosphorus level rose to a mean of 8.4 (± 1.9) mg/dl, at a median of 4 hours after the administration of the second 30-gram dose of sodium phosphate tablets. the serum phosphorus level remained above baseline for a median of 24 hours after the administration of the initial dose of sodium phosphate tablets (range 16 to 48 hours). figure 1. mean (±standard deviation) serum phosphorus concentrations the upper (4.5 mg/dl) and lower (2.6 mg/dl) reference limits for serum phosphate are represented by solid bars. specific populations male and female patients : no difference in serum phosphate auc values were observed in the single pharmacokinetic study conducted with sodium phosphate tablets in 13 male and 10 female healthy subjects. elderly patients : in a single pharmacokinetic study of sodium phosphate tablets, which included 6 elderly subjects, plasma half-life increased two-fold in subjects > 70 years of age compared to subjects < 50 years of age (3 subjects and 5 subjects, respectively) [see use in specific populations (8.5) ] . patients with renal impairment : the effect of renal impairment on the pharmacokinetics of monobasic sodium phosphate and dibasic sodium phosphate tablets has not been studied. the inorganic form of phosphate in the circulating plasma is excreted almost entirely by the kidneys [see warnings and precautions (5.1) , use in specific populations (8.6) ]. graph

dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) was repeated the following morning beginning at 6 am. twenty-three healthy subjects (mean age 57 years old; 57% male and 43% female; and 65% hispanic, 30% caucasian, and 4% african-american) participated in this pharmacokinetic study. the serum phosphorus level rose from a mean (± standard deviation) baseline of 4.0 (± 0.7) mg/dl to 7.7 (± 1.6 mg/dl), at a median of 3 hours after the administration of the first 30-gram dose of sodium phosphate tablets (see figure 1 ). the serum phosphorus level rose to a mean of 8.4 (± 1.9) mg/dl, at a median of 4 hours after the administration of the second 30-gram dose of sodium phosphate tablets. the serum phosphorus level remained above baseline for a median of 24 hours after the administration of the initial dose of sodium phosphate tablets (range 16 to 48 hours). figure 1. mean (±standard deviation) serum phosphorus concentrations the upper (4.5 mg/dl) and lower (2.6 mg/dl) reference limits for serum phosphate are represented by solid bars. specific populations male and female patients : no difference in serum phosphate auc values were observed in the single pharmacokinetic study conducted with sodium phosphate tablets in 13 male and 10 female healthy subjects. elderly patients : in a single pharmacokinetic study of sodium phosphate tablets, which included 6 elderly subjects, plasma half-life increased two-fold in subjects > 70 years of age compared to subjects < 50 years of age (3 subjects and 5 subjects, respectively) [see use in specific populations (8.5) ] . patients with renal impairment : the effect of renal impairment on the pharmacokinetics of monobasic sodium phosphate and dibasic sodium phosphate tablets has not been studied. the inorganic form of phosphate in the circulating plasma is excreted almost entirely by the kidneys [see warnings and precautions (5.1) , use in specific populations (8.6) ].

the colonoscopy and 18 grams on the next day) with 2 quarts of clear liquids. patients were instructed to eat a light breakfast before noon on the day prior to the colonoscopy and then were told to drink only clear liquids after noon on the day prior to the colonoscopy. the primary efficacy endpoint was the overall colon cleansing response rate in the 4-point colonic contents scale. response was defined as a rating of "excellent" or "good" on the 4-point scale as determined by the blinded colonoscopist. this trial was designed to assess the non-inferiority of the two monobasic sodium phosphate and dibasic sodium phosphate tablets groups compared to the active control group. the efficacy analysis included 704 adult patients who had an elective colonoscopy. patients ranged in age from 21 to 89 years old (mean age 56 years old) with 55% female and 45% male patients. race was distributed as follows: 87% caucasian, 10% african american, and 3% other race. the monobasic sodium phosphate and dibasic sodium phosphate tablets 60-gram and 48-gram treatment groups demonstrated non-inferiority compared to the active control. see table 2 for the results. 1colon cleansing efficacy was based on response rate to treatment. a patient was considered to be a responder if overall colon cleansing was rated as "excellent" or "good" on a 4-point scale based on the amount of retained "colonic contents". excellent was defined as >90% of mucosa seen, mostly liquid stool, minimal suctioning needed for adequate visualization. good was defined as >90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization. fair was defined as >90% of mucosa seen, mixture of liquid and semisolid stool, could be suctioned and/or washed. inadequate was defined as <90% of mucosa seen, mixture of semisolid and solid stool which could not be suctioned or washed. 2on the day of the colonoscopy, study medication was taken 3 to 5 hours before the start of the colonoscopy. table 2: phase 3 study – overall colon content cleansing response rates 1 treatment arm (grams of sodium phosphate) no. of tablets taken at 6 pm on the day prior to colonoscopy no. of tablets taken the next day 2 excellent good fair inadequate overall response rate (excellent or good) monobasic sodium phosphate and dibasic sodium phosphate tablets 32 tabs (48 g) n=236 20 12 76% 19% 3% 2% 95% monobasic sodium phosphate and dibasic sodium phosphate tablets 40 tabs (60 g) n=233 20 20 73% 24% 2% 1% 97% sodium phosphate tablets 40 tabs (60 g) n=235 20 20 51% 43% 6% 0% 94% the monobasic sodium phosphate and dibasic sodium phosphate tablets 60-gram dosage regimen had a similar overall response rate as the 48-gram dosage regimen and was associated with an increased risk of adverse reactions [see adverse reactions (6.1) ] . therefore, the monobasic sodium phosphate and dibasic sodium phosphate tablets 60-gram dosage is not a recommended regimen [see dosage and administration (2.2) ].

ed portion.