Indications and Usage
OsmoPrep Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older.
Dosage and Administration
The recommended dose of OsmoPrep 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 procedure:Take 4 OsmoPrep Tablets with 8 ounces of clear liquids every 15 minutes for a total of 20 tablets.
On the day of the colonoscopy procedure:
Starting 3-5 hours before the procedure, take 4 OsmoPrep Tablets with 8 ounces of clear liquids every 15 minutes for a total of 12 tablets.
Patients should be advised of the importance of taking the recommended fluid regimen. It is recommended that patients receiving OsmoPrep be advised to adequately hydrate before, during, and after the use of OsmoPrep.
Patients should not use OsmoPrep for colon cleansing within seven days of previous administration. No additional enema or laxative is required, and patients should be advised NOT to take additional agents, particularly those containing sodium phosphate.
Contraindications
OsmoPrep Tablets are contraindicated in patients with biopsy-proven acute phosphate nephropathy.
OsmoPrep Tablets are contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients.
Adverse Reactions
Abdominal bloating, abdominal pain, nausea, and vomiting were the most common adverse events reported with the use of OsmoPrep Tablets. Dizziness and headache were reported less frequently. Since diarrhea was considered as a part of the efficacy of OsmoPrep, diarrhea was not defined as an adverse event in the clinical studies. Table 2 shows the most common adverse events associated with the use of 48 grams of OsmoPrep, 60 grams of OsmoPrep, and 60 grams of Visicol in the colon preparation trials (n=931).
|
Table 2: Frequency
of Adverse Events of Any Severity Occurring in Greater Than 3% of Patients in the OsmoPrep Trials |
|||
| OsmoPrep 32 tabs (48 g) N=272 |
OsmoPrep 40 tabs (60 g) N=265 |
Visicol 40 tabs (60 g) N=268 |
|
|---|---|---|---|
| Bloating | 31% | 39% | 41% |
| Nausea | 26% | 37% | 30% |
| Abdominal Pain | 23% | 24% | 25% |
| Vomiting | 4% | 10% | 9% |
Postmarketing Experience
In addition to adverse events reported from clinical trials, the following adverse events have been identified during post-approval use of OsmoPrep. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to OsmoPrep, or a combination of these factors.
General: Hypersensitivity reactions including anaphylaxis, rash, pruritus, urticaria, throat tightness, bronchospasm, dyspnea, pharyngeal edema, dysphagia, paresthesia and swelling of the lips and tongue, and facial swelling.
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.
Drug Abuse and Dependence
Laxatives and purgatives (including OsmoPrep) have the potential for abuse by bulimia nervosa patients who frequently have binge eating and vomiting.
Overdosage
There have been no reported cases of overdosage with OsmoPrep Tablets. Purposeful or accidental ingestion of more than the recommended dosage of OsmoPrep Tablets might be expected to lead to severe electrolyte disturbances, including hyperphosphatemia, hypocalcemia, hypernatremia, or hypokalemia, as well as dehydration and hypovolemia, with attendant signs and symptoms of these disturbances. Certain severe electrolyte disturbances resulting from overdose may lead to cardiac arrhythmias, seizure, renal failure, and death. The patient who has taken an overdosage should be monitored carefully, and treated symptomatically for complications until stable.
Description
OsmoPrep® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) is a purgative used to clean the colon prior to colonoscopy. OsmoPrep is manufactured with a highly soluble tablet binder and does not contain microcrystalline cellulose (MCC). OsmoPrep Tablets are oval, white to off-white compressed tablets, debossed with “SLX” on one side of the bisect and “102” on the other side of the bisect. Each OsmoPrep tablet contains 1.102 grams of sodium phosphate monobasic monohydrate, USP and 0.398 grams of sodium phosphate dibasic anhydrous, USP for a total of 1.5 grams of sodium phosphate per tablet. Inert ingredients include polyethylene glycol 8000, NF; and magnesium stearate, NF. OsmoPrep is gluten-free.
The structural and molecular formulae and molecular weights of the active ingredients are shown below:
- Sodium phosphate monobasic monohydrate, USP
Molecular Formula: NaH2PO4 • H2O
Molecular Weight: 137.99
- Sodium phosphate dibasic anhydrous, USP
Molecular Formula: Na2HPO4
Molecular Weight: 141.96
OsmoPrep Tablets are for oral administration only.
image of chem structure 1 image of chem structure 2Clinical Pharmacology
OsmoPrep Tablets, a dosing regimen containing 48 grams of sodium phosphate (32 tablets), induces diarrhea, which effectively cleanses the entire colon. Each administration has a purgative effect for approximately 1 to 3 hours. The primary mode of action is thought to be through the osmotic effect of sodium, causing large amounts of water to be drawn into the colon, promoting evacuation.
Pharmacokinetics
Pharmacokinetic studies with OsmoPrep have not been conducted. However, the following pharmacokinetic study was conducted with Visicol® tablets which contain the same active ingredients (sodium phosphate) as OsmoPrep. In addition, Visicol is administered at a dose that is 25% greater than the OsmoPrep dose.
An open-label pharmacokinetic study of Visicol in healthy volunteers was performed to determine the concentration-time profile of serum inorganic phosphorus levels after Visicol administration. All subjects received the approved Visicol dosing regimen (60 grams of sodium phosphate with a total liquid volume of 3.6 quarts) for colon cleansing. 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.
Special Populations
Renal Insufficiency: The effect of renal dysfunction on the pharmacokinetics of OsmoPrep Tablets has not been studied. Since the inorganic form of phosphate in the circulating plasma is excreted almost entirely by the kidneys, patients with renal disease may have difficulty excreting a large phosphate load. Thus, OsmoPrep Tablets should be used with caution in patients with impaired renal function (see WARNINGS).
Hepatic Insufficiency: OsmoPrep Tablets have not been investigated in patients with hepatic failure.
Geriatric: In a single pharmacokinetic study of sodium phosphate tablets, which included 6 elderly volunteers, plasma half-life increased two-fold in subjects greater than 70 years of age compared to subjects less than 50 years of age (3 subjects and 5 subjects, respectively).
Gender: 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 volunteers.
image of figure 1
Clinical Studies
The colon cleansing efficacy and safety of OsmoPrep was evaluated in 2 randomized, investigator-blinded, actively controlled, multicenter, U.S. trials in patients scheduled to have an elective colonoscopy. The trials consisted of a dose ranging and a confirmatory phase 3 study.
In the phase 3 trial, patients were randomized into one of the following three sodium phosphate treatment groups: 1) Visicol containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with at least 3.6 quarts of clear liquids; 2) OsmoPrep containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with 2.5 quarts of clear liquids; and 3) OsmoPrep containing 48 grams of sodium phosphate (30 grams in the evening before 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 phase 3 study was planned to assess the non-inferiority of the two OsmoPrep groups compared to the Visicol 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 OsmoPrep 60 gram and 48 gram treatment groups demonstrated non-inferiority compared to Visicol. See Table 1 for the results.
|
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 day2 |
Excellent
|
Good
|
Fair
|
Inadequate
|
Overall Response Rate (Excellent or Good) |
| OsmoPrep 32 tabs (48 g) n = 236 |
20 |
12 |
76% |
19% |
3% |
2% |
95% |
| OsmoPrep 40 tabs (60 g) n = 233 |
20 |
20 |
73% |
24% |
2% |
1% |
97% |
| Visicol 40 tabs (60 g) n = 235 |
20 |
20 |
51% |
43% |
6% |
0% |
94% |
Colon-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 greater than 90% of mucosa seen, mostly liquid stool, minimal suctioning needed for adequate visualization. Good was defined as greater than 90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization. Fair was defined as greater than 90% of mucosa seen, mixture of liquid and semisolid stool, could be suctioned and/or washed. Inadequate was defined as less than 90% of mucosa seen, mixture of semisolid and solid stool which could not be suctioned or washed.
2
On the day of the colonoscopy, study medication was taken 3 to 5 hours before the start of the colonoscopy.
the day of the colonoscopy, study medication was taken 3 to 5 hours before the start of the colonoscopy.
How Supplied / Storage and Handling
OsmoPrep Tablets are supplied in child-resistant bottles containing 32 tablets. Each tablet contains 1.102 g sodium phosphate monobasic monohydrate, USP and 0.398 g sodium phosphate dibasic anhydrous, USP for a total of 1.5 g of sodium phosphate per tablet.
| NDC 54868-5889-1 |
Bottles of 04 |
| NDC 54868-5889-0 |
Bottles of 32 |
Rx only.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature]. Discard any unused portion.
Manufactured by:
WellSpring Pharmaceutical Canada
Corp.
Oakville, Ontario Canada L6H 1M5
for:
Salix Pharmaceuticals, Inc.
Morrisville, NC 27560
Made in Canada
VENART-30-4/Mar. 2009
Product protected by US Patent No. 5,616,346 and other pending applications.
Relabeling and Repackaging by:
Physicians Total Care, Inc.
Tulsa, OK 74146