Colorectal cancer (CRC) is the third most commonly diagnosed cancer in
the United States, resulting in the second highest rate of cancer-related
mortality.1 Routine screening of asymptomatic adults has been shown to
significantly reduce incidence of CRC.2 Detection of CRC at an early
localized stage is associated with a 5-year survival rate of 90%.3 Current
guidelines recommend colonoscopy, starting at 50 years of age for
average risk individuals, as the preferred screening method to promote
early detection and removal of polyps and precancerous lesions that
may lead to CRC.4
Despite the evidence supporting the effectiveness of colorectal screening, less than half of the US population aged 50 years and older
undergoes screening colonoscopy.5,6 Patient reluctance to undergo
screening procedures may contribute to low screening rates. In a survey
of patients who had and had not participated in screening colonoscopy,
the need for bowel preparation was identified as the most objectionable
aspect of colonoscopy.7 The importance of a high-quality bowel
preparation for the detection of polyps has been demonstrated in several
studies.8-10 Patients who are either unable or unwilling to complete a
colon-cleansing regimen may have inadequate bowel cleansing, which
can result in incomplete visualization of the colon and failure to detect
colon pathology.11 Furthermore, poor bowel preparation may have a
substantial economic impact by prolonging procedure time and
increasing the chance of an aborted examination, thereby necessitating
a repeat colonoscopy at an interval sooner than that recommended by
the guidelines. Therefore, improvements in bowel preparation tolerability
are paramount for increasing patient compliance with CRC screening
guidelines, which in turn can lead to improved outcomes of colonoscopy.
Split dosing of bowel preparations for colonoscopy has recently emerged
as an important factor in bowel cleansing efficacy and may also impact
patient tolerability. In an effort to improve the quality of colonoscopy, the
2008 American College of Gastroenterology guidelines for CRC
screening recommend that bowel preparations be given in split doses
and that this regimen be considered the standard of care.4 In this
newsletter, efficacy, potential concerns, and patient tolerability and
acceptability of split dosing of bowel purgatives in preparation for
colonoscopy are reviewed.
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Commercially available bowel preparations include polyethylene glycol electrolyte lavage solutions
(PEG-ELS; available as 4-L solutions and as reduced-volume 2-L solutions), sodium phosphate (NaP)
preparations (available in tablet form), and oral sulfate solutions (OSS; Table 1).
The early development of bowel preparation products emphasized increasing efficacy, safety, and patient tolerability of the
bowel-cleansing process. However, the timing of cathartics and fasting requirements adopted from the earliest days of bowel
preparation for colonoscopy remained unchanged. In the mid-1990s, investigators began to test the requirement to complete the
bowel preparation the day before the procedure. Subsequently, a number of studies demonstrated that both NaP and PEG-ELS
bowel preparations achieved more optimal bowel cleansing, especially in the right or ascending colon, with a split-dose regimen
versus evening-only dosing.12,13 Split-dose regimens, in which half of the formulation is taken the evening before the colonoscopy
and the rest is taken the morning of the procedure (PM/AM dosing), have been shown to improve colon cleansing compared with
the conventional regimen (the entire dose taken the day before the procedure; Figures 1 and 2).
Figure 1. The PM/AM split-dosing regimen. NPO = nothing by mouth.
A 
B 
Figure 2. Conventional PM only dosing versus PM/AM split-dosed bowel preparations.
A) cecum after PM only dosing and B) cecum after PM/AM split dosing.14
Split dosing, which can be carried out with PEG-ELS, NaP, or OSS, helps maximize the time between the 2 doses of the bowel
preparation and minimize the interval between the time the last dose of the purgative is taken and the start time of the colonoscopy.
Although many bowel preparations have been used as split doses, MoviPrep®, OsmoPrep®, Visicol®, and Suprep® are the only
bowel preparation formulations currently approved by the US Food and Drug Administration as split-dose regimens.
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Improved Quality of Bowel Preparation
Sodium phosphate and PEG-ELS bowel preparations have shown optimal cleansing when a split-dose regimen is followed.15 In a study with 4-L PEG-ELS, patients receiving a PM/AM split-dose preparation were significantly more likely to have their preparation rated excellent by the clinician than patients receiving the entire preparation the evening before colonoscopy (44% vs 6%, respectively; Figure 3) .13
Figure 3. Improved quality of bowel preparation with PM/AM split dosing compared with PM/AM dosing. Patients who received a PM/AM split dose of 4-L PEG-ELS were significantly more likely to have the quality of their preparation rated excellent than patients who received the entire 4-L dose the evening before colonoscopy. Reprinted from Gastrointestinal Endoscopy; Vol 62; Aoun E, Abdul-Baki H, Azar C, et al; A randomized single-blind trial of split-dose PEG-electrolyte solution without dietary restriction compared with whole dose PEG-electrolyte solution with dietary restriction for colonoscopy preparation; Pages 213-218; Copyright 2005, with permission from the American Society for Gastrointestinal Endoscopy. 13
One of the main concerns with respect to bowel preparations administered entirely the day before the procedure is the potential for
impaired visualization of the colon because of residual fecal matter, particularly in the right colon.12 Passage of chyme from the
small intestine to the cecum and ascending colon during the 10 to 14 hours between final administration of the purgative and onset
of the procedure may make the visualization of mucosal detail difficult. In addition, continuous gastric, intestinal, pancreatic, and
biliary secretions also may result in reaccumulation of small-intestinal effluent in the colon. In one study, PM/AM split dosing of NaP
solution resulted in significantly less fecal material in the right colon compared with NaP solution administered the day before the
procedure.12 Furthermore, the bowel fluid was typically translucent in the PM/AM split-dosed group, whereas the fluid was opaque
in the group taking the solution the day before the procedure.
Enhanced Detection of Flat Polyps
Another measure of the improved cleansing efficacy of a split-dose regimen compared with a conventional previous-day dosing
regimen of bowel preparation is the potentially enhanced detection of nonpolypoid flat lesions. Flat lesions are hard to differentiate
endoscopically from normal mucosa because flat lesions present with only subtle differences.16 These lesions have a greater
association with CRC than polypoid adenomas of similar size at the time of detection. Furthermore, the lesions in the right colon are
more often flat, which may contribute to the increased incidence of right-sided CRC compared with the overall rate of CRC.17 In a
study evaluating a PM/AM split-dose regimen, dosing the morning of the procedure (AM dosing), and dosing the day before the
procedure (PM dosing), both PM/AM and AM dosing demonstrated superior colon cleansing compared with PM dosing.18 In addition,
detection of flat lesions was significantly greater in the PM/AM and AM dosing groups than in the PM dosing groups. These results
provide further evidence that improvement in the quality of bowel preparation associated with PM/AM split dosing is associated
mainly with the second purgative dose (AM dose) administered the same day as the colonoscopy.18,19 Additionally, bowel
preparation quality varies inversely with the duration of the interval between the time the last purgative dose is taken and the start
time of the colonoscopy,20 which is more important than the interval between the 2 purgative doses in the PM/AM split-dose regimen.
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Compliance With American Society of Anesthesiologists Fasting Guidelines
Although PM/AM split dosing results in improved bowel-cleansing efficacy, some endoscopists may be reluctant to adopt such a
regimen because of misconceptions. One main concern is the confusion based on the belief that the second purgative dose is not
compliant with preprocedure fasting guidelines from the American Society of Anesthesiologists (ASA). The common
misunderstanding is that patients undergoing anesthesia should not eat or consume liquids after midnight the day before the
procedure. Guidelines of the ASA support a 2-hour period of nothing by mouth before sedation for all patients, which allows
patients to remain well hydrated.21 A PM/AM split-dosing regimen will not interfere with these guidelines if the second dose is
completed at least 2 hours before colonoscopy (Table 2).
The basis of fasting before sedation is to avoid the risk of potential pulmonary aspiration from residual gastric contents. However, a light meal is emptied from the stomach in 1.5 to 3 hours, and clear fluids are emptied almost immediately. In a prospective, randomized study, there were no significant differences in residual gastric volume and pH in patients who consumed clear liquids up to 2 hours versus 6 hours before the procedure (Table 3).22
Additionally, the risk of dehydration is reduced if clear liquids are consumed up to 2 hours before sedation.
Risk of Fecal Incontinence
Another concern of physicians and patients is the risk of fecal incontinence en route to the endoscopy center. This is a logical concern for patients after any bowel preparation regimen. However, prospective studies demonstrated that the percentage of patients requiring a bathroom stop in transit to the endoscopy center was similar with both PM/AM split-dose and conventional previous-day regimens (9% vs 5%; P=NS; Table 4).23
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Clinicians are sometimes reluctant to prescribe a split-dose regimen based on the concern that patients may not be willing to
comply with the early morning administration of the second dose. Although patients may not prefer to wake up early in the morning
to ingest the second dose, most patients are willing to comply once they understand the benefits of PM/AM split dosing (Figure 4).14
Figure 4. A majority of patients are willing to rise early to take the second dose of the preparation in a survey.24 Survey participants included
endoscopy patients and drivers of colonoscopy patients.
In a recent survey, 85% of respondents were willing to awaken as early as 2 AM or 3 AM to take the second dose.24 In a
comparative study, patients taking a PM/AM split-dose formulation were more often satisfied with the bowel preparation than those
who took the purgative entirely the evening before (63% vs 46%; P<0.0001).23 Fewer patients found the PM/AM split-dosing
regimen difficult to finish compared with the evening-only regimen (19% vs 44%). In a study of 4-L PEG-ELS administered as
PM/AM split dosing versus previous-day dosing, the volume of the preparation was better tolerated and patients were more willing
to repeat the split-dose regimen than the conventional previous-day dosing regimen.25 Results from these studies demonstrate that
a PM/AM split-dosing regimen is well accepted by patients, and waking early to take the second purgative dose is not a concern if
patients are convinced that the regimen will improve the outcome of their colonoscopy.
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With patient acceptance, convenience, and an improved efficacy, PM/AM split dosing is an effective strategy to optimize colon
cleansing and should be considered the standard of care. The timing of the second dose being less than 6 hours before
examination is considered critical for the quality of bowel preparation. Also, by maximizing the time between the 2 doses, PM/AM
split dosing may minimize the risk of dehydration associated with bowel preparations. By improving the quality of bowel preparation
and potentially the detection of flat lesions, a PM/AM split-dose regimen may increase the overall efficiency of colonoscopy and
CRC screening.
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Important Safety Information about MOVIPREP
MOVIPREP® (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 18 years of age or older. MOVIPREP is contraindicated in patients with gastrointestinal (GI) obstruction, bowel perforation, gastric retention, ileus, toxic colitis or toxic megacolon, and patients who have had a severe hypersensitivity reaction to any of its components. MOVIPREP should be used with caution in patients at risk of or with fluid and electrolyte abnormalities, hyponatremia, arrhythmias, seizures, in patients with impaired renal function or patients taking concomitant medications that affect renal function, patients with known or suspected inflammatory bowel disease, patients with suspected GI obstruction or perforation, patients at risk for aspiration, and patients with glucose-6-phosphate dehydrogenase deficiency. Most common adverse reactions for split dosing (incidence = 5%) are malaise, nausea, abdominal pain, vomiting, and upper abdominal pain. The most common adverse reactions for evening only dosing (incidence = 5%) are abdominal distension, anal discomfort, thirst, nausea, abdominal pain, sleep disorder, rigors, hunger, malaise, vomiting, and dizziness. MOVIPREP contains 233 mg of phenylalanine per treatment. Advise patients to hydrate adequately before, during, and after the use of MOVIPREP.
For complete Prescribing Information.
Important Safety Information about OSMOPREP
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior
to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some
cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with
increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers
[ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
OSMOPREP® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing
of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OSMOPREP is used in
patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation,
bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal
function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte
disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as
hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OSMOPREP.
OSMOPREP is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with
biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were
abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OSMOPREP be advised to adequately hydrate before,
during, and after the use of OsmoPrep.
For complete Prescribing Information for OSMOPREP including BOXED WARNING.
Important Safety Information about VISICOL
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium
phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal
function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable
risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia,
increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors,
angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
VISICOL®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for
cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older.
VISICOL is not to be used in patients with congestive heart failure, ascites, unstable angina pectoris, gastric retention,
ileus or acute obstruction or pseudo-obstruction, severe chronic constipation, bowel perforation, acute colitis, toxic
megacolon, or hypomotility syndrome. Use with caution in patients with impaired renal function, pre-existing electrolyte
disturbances, or people taking drugs that affect electrolyte levels. VISICOL is contraindicated in patients with a known
allergy or hypersensitivity to sodium phosphate salts or any of its ingredients. In clinical trials, the most commonly
observed (=1%) adverse reactions occurring with use of VISICOL were generally transient and self-limited and included
nausea, vomiting, abdominal bloating, abdominal pain, dizziness and headache.
Consult with your physician to see if this product is right for you.
Complete Prescribing Information for VISICOL, including BOXED WARNING
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