PICOPREP

(sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution is a stimulant and osmotic laxative that is provided as a cranberry-flavored, colorless to slightly yellow, clear solution with possible presence of visible particles.

CLENPIQ is supplied as two bottles in each carton.

Each bottle of

CLENPIQ contains 10 mg sodium picosulfate, USP; 3.5 g magnesium oxide, USP; and 12 g anhydrous citric acid, USP.

The product also contains the following inactive ingredients: acesulfame potassium, cranberry flavor, disodium edetate, malic acid, sodium benzoate, sodium hydroxide, sodium metabisulfite, sucralose, and water.

The cranberry flavor contains glyceryl triacetate (triacetin), maltodextrin, and sodium octenyl succinated starch.

The following is a description of the three active ingredients contained in CLENPIQ: Sodium picosulfate is a stimulant laxative.

Chemical name: 4,4´-(2-pyridylmethylene) diphenyl bis(hydrogen sulfate) disodium salt, monohydrate Chemical formula: C 18 H 13 NNa 2 O 8 S 2 ∙H 2 O Molecular weight: 499.4 Structural formula: Sodium picosulfate Magnesium citrate, which is formed in solution by the combination of magnesium oxide and anhydrous citric acid, is an osmotic laxative.

Chemical Structure Magnesium Oxide Chemical name

Magnesium oxide Chemical formula: Mg O Molecular weight: 40.3 Structural formula: Mg O Anhydrous Citric Acid Chemical name: 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical formula: C 6 H 8 O 7 Molecular weight: 192.1 Structural formula: Anhydrous citric acid Chemical Structure.

Carefully used under the supervision of a doctor in the following cases: during pregnancy and lactation; heart patients; ulcers; stomach or intestinal problems; persons with low-skinned diet.

Sodium picosulfate is hydrolyzed by colonic bacteria to form an active metabolite: bis-(p-hydroxy-phenyl)-pyridyl-2-methane, BHPM, which acts directly on the colonic mucosa to stimulate colonic peristalsis.

Magnesium oxide and citric acid react to create magnesium citrate in solution, which is an osmotic agent that causes water to be retained within the gastrointestinal tract. 12.2 Pharmacodynamics The stimulant laxative activity of sodium picosulfate together with the osmotic laxative activity of magnesium citrate produces a purgative effect which, when ingested with additional liquids, produces watery diarrhea. 12.3 Pharmacokinetics Absorption After administration of the first dose of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product in 16 healthy subjects, the mean ± SD maximum plasma concentration (C max ) for picosulfate of 2.3 ± 1.4 ng/mL was reached at 2 hours.

After administration of two doses separated by 6 hours, the mean ± SD plasma C max for picosulfate of 3.2 ± 2.6 ng/mL was reached at approximately 7 hours after the first dose administration.

In the same study, the uncorrected plasma magnesium concentration reached a C max of approximately 1.9 mEq/L at 10 hours after the first dose administration, which represents an approximately 20% increase from baseline.

In patients scheduled to have an elective colonoscopy who received the Split-Dose dosage regimen of CLENPIQ, the mean ± SD plasma concentration for picosulfate was 1.05 ± 0.83 ng/mL at 15 minutes pre-second dose, 2.98 ± 1.27 ng/mL at 1-2 hours post-second dose, and 1.81 ± 0.86 ng/mL at 3-6 hours post-second dose.

Metabolism and Elimination Metabolism and Excretion

Plasma concentrations of the free BHPM were below the lower limit of quantification (0.1 ng/mL) in 13 out of 16 subjects studied.

The fraction of the sodium picosulfate dose excreted unchanged in urine was 0.1%.

In urine, the majority of excreted BHPM was in the glucuronide-conjugated form.

The terminal half-life of sodium picosulfate was 7.4 hours.

Pharmacokinetics of picosulfate was studied in pediatric patients aged from to 16 years old.

The half-life of picosulfate was 7 hours.

The picosulfate reached the mean ± SD C max of 3.5 ± 2.1 ng/mL at approximately to 7 hours.

The baseline uncorrected mean serum magnesium concentration was 2.02 mEq/L at 10 hours after the first dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid and ranged from 1.7 to 2.46 mEq/L. Drug Interaction Studies In an in vitro study using human liver microsomes, sodium picosulfate did not inhibit the major CYP enzymes (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5) evaluated.

Based on an in vitro study using freshly isolated hepatocyte culture, sodium picosulfate is not an inducer of CYP1A2, CYP2B6, or CYP3A4/5.

This drug includes sodium picosulfate, which belongs to the magnesium oxide category, and is also produced by the presence of sterric acid, which is a magnesium cyclic, which belongs to the victim's easer category, which is to draw water in colon, which facilitates intestinal motion and excretion.

Overdosage of more than the recommended dose of CLENPIQ may lead to severe electrolyte disturbances, as well as dehydration and hypovolemia, with signs and symptoms of these disturbances.

Monitor for fluid and electrolyte disturbances and treat symptomatically.

is contraindicated in the following conditions: Patients with severe renal impairment (creatinine clearance less than 30 mL/minute), which may result in accumulation of magnesium.

Gastrointestinal obstruction or ileus.

Bowel perforation.

Toxic colitis or toxic megacolon.

Gastric retention.

Hypersensitivity to any of the ingredients in CLENPIQ.

Severe renal impairment (creatinine clearance less than 30 mL/minute) Gastrointestinal (GI) obstruction or ileus Bowel perforation Toxic colitis or toxic megacolon Gastric retention Hypersensitivity to any of the ingredients in CLENPIQ.

CLENPIQ is ready to drink.

It does not need to be diluted prior to administration.

One bottle of

CLENPIQ is equivalent to one dose.

Two doses of

CLENPIQ are required for a complete preparation for colonoscopy as a Split-Dose regimen.

Consume five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose.

Consume a variety of clear liquids after each dose of CLENPIQ.

Ensure inclusion of balanced electrolyte solution along with other clear liquids.

Administer oral medications at least 1 hour before starting CLENPIQ.

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 CLENPIQ.

For complete information on preparation before colonoscopy and administration of the dosage regimen, see full prescribing information.

First dose: administer during evening before the colonoscopy Second dose: administer the next day, during the morning prior to the colonoscopy. 2.1 Important Administration Instructions Correct fluid and electrolyte abnormalities before administration of CLENPIQ.

It is a clear solution with possible presence of visible particles and it does not need to be diluted prior to administration.

Split-Dose method consists of two separate doses: the first dose during the evening before the colonoscopy and the second dose the next day, during the morning prior to the colonoscopy.

Consume a variety of clear liquids.

Clear liquids should include balanced electrolyte solution.

Additional clear liquids, other than water, include black coffee or tea, plain jello, clear broth or bouillon, clear juices without pulp, ginger ale and other sodas, and frozen juice bars.

Do not drink anything colored red or purple.

Consume only clear liquids (no solid food) on the day before colonoscopy and until after the colonoscopy.

Do not eat solid food or dairy and do not drink anything colored red or purple.

Do not drink alcohol.

Stop consumption of all liquids at least 2 hours before the colonoscopy.

Do not take other laxatives while taking CLENPIQ.

Administer oral medications at least one hour before starting each dose of CLENPIQ.

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 CLENPIQ. 2.2 Split-Dose Dosage Regimen The recommended dosage in adults and pediatric patients 9 years of age and older is shown below.

Instruct patients to take two separate doses in conjunction with liquids, as follows: Dose 1 – On the day before colonoscopy: Instruct patients to consume only clear liquids (no solid food or dairy) on the day before the colonoscopy up until 2 hours before the time of the colonoscopy.

Take the first dose (1 bottle) of CLENPIQ during the evening before the colonoscopy (e.g., 5:00 PM to 9:00 PM).

Consume at least five 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose over the next 5 hours.

If severe bloating, distention, or abdominal pain occurs, following the first dose, delay the second dose until the symptoms resolve.

Dose 2 – Next morning on the day of colonoscopy (start approximately 5 hours prior to colonoscopy): Continue to consume only clear liquids (no solid food or dairy).

Take the second dose (the second bottle) of CLENPIQ.

Consume four or more 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose and up to 2 hours before the colonoscopy.

CLENPIQ is supplied in a carton containing two bottles, each holding 175 mL of cranberry-flavored, colorless to slightly yellow, clear oral solution with possible presence of visible particles.

Each bottle contains 10 mg sodium picosulfate, 3.5 g magnesium oxide, and 12 g anhydrous citric acid.

An eight-ounce cup for measuring liquids for hydration is also supplied.

CLENPIQ Cranberry flavor

NDC# 55566-6800-1.

CLENPIQ at 25°C (77°F).

Excursions permitted at 15°C to 30°C (59°F to 86°F). .

Do not refrigerate or freeze.

CLENPIQ at 25°C (77°F).

Excursions permitted at 15°C to 30°C (59°F to 86°F). .

Do not refrigerate or freeze.

Risk Summary There are no data with CLENPIQ use in pregnant women to determine a drug-associated risk of adverse developmental outcomes.

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats when sodium picosulfate, magnesium oxide, and anhydrous citric acid were administered orally at doses 1.2 times the recommended human dose based on body surface area during organogenesis.

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 to 4% and to 20%, respectively.

Reproduction studies with sodium picosulfate, magnesium oxide, and anhydrous citric acid have been performed in pregnant rats following oral administration of up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area) during the period of organogenesis.

There was no evidence of harm to the fetus due to sodium picosulfate, magnesium oxide, and anhydrous citric acid.

The reproduction study in rabbits was not adequate, as treatment-related mortalities were observed at all doses.

A pre and postnatal development study with sodium picosulfate, magnesium oxide, and anhydrous citric acid in rats showed no evidence of any adverse effect on pre and postnatal development at oral doses up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area).

Published reproduction studies with sodium picosulfate in pregnant rats and rabbits during the period of organogenesis did not show evidence of harm to the fetus at doses up to 100 mg/kg (approximately and 98 times, respectively, the recommended human dose of 10 mg sodium picosulfate based on body surface area).

The safety and effectiveness of

CLENPIQ have been established for cleansing of the colon as a preparation for colonoscopy in pediatric patients 9 years of age and older.

Use of

CLENPIQ in this is supported by evidence from adequate and well-controlled trials in adults and a single, dose-ranging, controlled trial in 78 pediatric patients to 16 years of age all of which evaluated another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid.

The safety profile in this pediatric population was similar to that seen in adults.

Monitor for possible hypoglycemia in pediatric patients, as CLENPIQ has no caloric substrate.

CLENPIQ in pediatric patients less than 9 years of age have not been established.

Of the 448 adult patients in Study 1 who received CLENPIQ, 124 (28%) patients were 65 years of age or older.

No overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients.

Elderly 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.