Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer
2014; Lippincott Williams & Wilkins; Volume: 109; Issue: 10 Linguagem: Inglês
10.1038/ajg.2014.272
ISSN1572-0241
AutoresDavid A. Johnson, Alan Barkun, Larry Cohen, Jason A. Dominitz, Tonya Kaltenbach, Myriam Martel, Douglas J. Robertson, C. Richard Boland, Frances M. Giardello, David A. Lieberman, Theodore R. Levin, Douglas K. Rex,
Tópico(s)Colorectal Cancer Surgical Treatments
ResumoColorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States (1) Colonoscopy can prevent CRC by the detection and removal of precancerous lesions. In addition to CRC screening and surveillance, colonoscopy is used widely for the diagnostic evaluation of symptoms and other positive CRC screening tests. Regardless of indication, the success of colonoscopy is linked closely to the adequacy of preprocedure bowel cleansing. Unfortunately, up to 20–25% of all colonoscopies are reported to have an inadequate bowel preparation (2, 3) The reasons for this range from patient-related variables such as compliance with preparation instructions and a variety of medical conditions that make bowel cleansing more difficult to unit-specific factors (eg, extended wait times after scheduling of colonoscopy) (4) Adverse consequences of ineffective bowel preparation include lower adenoma detection rates, longer procedural time, lower cecal intubation rates, increased electrocautery risk, and shorter intervals between examinations (3, 5, 6, 7) Bowel preparation formulations intended for precolonoscopy cleansing are assessed based on their efficacy, safety, and tolerability. Lack of specific organ toxicity is considered to be a prerequisite for bowel preparations. Between cleansing efficacy and tolerability, however, the consequences of inadequate cleansing suggest that efficacy should be a higher priority than tolerability. Consequently, the choice of a bowel cleansing regimen should be based on cleansing efficacy first and patient tolerability second. However, efficacy and tolerability are closely interrelated. For example, a cleansing agent that is poorly tolerated and thus not fully ingested may not achieve an adequate cleansing. The goals of this consensus document are to provide expert, evidence-based recommendations for clinicians to optimize colonoscopy preparation quality and patient safety. Recommendations are provided using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) scoring system, which weighs the strength of the recommendation and the quality of the evidence (8) Methods Search Strategy Computerized medical literature searches were conducted from January 1980 (first year of approval of polyethylene glycol–electrolyte lavage solution [PEG-ELS]–based preparation by the Food and Drug Administration [FDA]) up to August 2013 using MEDLINE, PubMed EMBASE, Scopus, CENTRAL, and ISI Web of knowledge. We used a highly sensitive search strategy to identify reports of randomized controlled trials (9) with a combination of medical subject headings adapted to each database and text words related to colonoscopy and gastrointestinal agents, bowel preparation, generic name, and brand name. The complete search terms are available in Appendix A. Recursive searches and cross-referencing also were performed using a "similar articles" function; hand searches of articles were identified after an initial search. We included all fully published adult human studies in English or French. A systematic review of published articles and abstracts presented at national meetings was performed to collect and select the evidence. A meta-analysis and consensus agreement were used to analyze the evidence. Expert consensus was used to formulate the recommendations. The GRADE system was used to rate the strength of the recommendations. The guideline was reviewed by committees of and approved by the governing boards of the member societies of the Multi-Society Task Force on Colorectal Cancer (American College of Gastroenterology, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy). Effect of inadequate preparation on polyp/adenoma detection and recommended follow-up intervals Recommendations Preliminary assessment of preparation quality should be made in the rectosigmoid colon, and if the indication is screening or surveillance and the preparation clearly is inadequate to allow polyp detection greater than 5 mm, the procedure should be either terminated and rescheduled or an attempt should be made at additional bowel cleansing strategies that can be delivered without cancelling the procedure that day (Strong recommendation, low-quality evidence). If the colonoscopy is complete to cecum, and the preparation ultimately is deemed inadequate, then the examination should be repeated, generally with a more aggressive preparation regimen, within 1 year; intervals shorter than 1 year are indicated when advanced neoplasia is detected and there is inadequate preparation (Strong recommendation, low-quality evidence). If the preparation is deemed adequate and the colonoscopy is completed then the guideline recommendations for screening or surveillance should be followed (Strong recommendation, high-quality evidence). Inadequate colonic preparation is associated with reduced adenoma detection rates (ADRs). A large prospective European study of 5832 patients enrolled in 21 centers across 11 countries examined the association of preparation quality and polyp identification during colonoscopy performed for a range of common indications. High-quality preparation was associated with identification of polyps of all sizes (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.28–2.36), and with polyps greater than 10 mm in size (OR, 1.72; 95% CI, 1.11–2.67) (2) An analysis of a national endoscopic database examined the association of preparation quality and polyp identification in 93,004 colonoscopies (3) Colon preparation (as entered by the endoscopist at the time of the procedure) was dichotomized into adequate (excellent, good, and fair/adequate) and inadequate (fair, inadequate, and poor). In adjusted models, adequate preparation was predictive of detection of all polyps (OR, 1.21; 95% CI, 1.16–1.25), but not polyps greater than 9 mm and/or suspected cancer (OR, 1.5; 95% CI, 0.98–1.11). Similarly, a single-center study based at a US Veterans Affairs Medical Center examined preparation quality and ADRs in 8800 colonoscopies performed between 2001 and 2010 (10) When comparing those examinations with an inadequate/poor preparation (n=829) with those with an adequate preparation (n=5162), overall polyp detection was reduced (OR, 0.66; 95% CI, 0.56–0.83). Two retrospective single-center studies examined the association of preparation quality and adenoma miss rates when the preparation was considered inadequate and the examination was repeated within a short interval (11, 12) Miss rates were the total adenomas found on the second examination divided by the total adenomas found on both examinations. In 1 study (11) there were 12,787 colonoscopies with 3047 (24%) suboptimal preparations (fair or poor). Repeat colonoscopy within 3 years in 216 individuals who achieved adequate preparation showed an overall adenoma miss rate of 42%, and a miss rate of 27% for lesions 10 mm or larger in size. The other study identified 373 average-risk screening patients with poor or inadequate preparation (12) Repeat colonoscopy in 133 patients (77% achieved excellent or good preparation) showed a 47% overall adenoma miss rate. A single prospective Korean study evaluated 277 individuals after a complete colonoscopy and then a per-protocol repeat "tandem" colonoscopy within 3 months of the initial examination (13) The patient adenoma miss rate increased as baseline preparation quality decreased on the Aronchick scale. In the 19 patients with poor preparation the adenoma and advanced adenoma miss rates were 47% and 37%, respectively, compared with 21% and 9% in those with excellent preparation (P=.024). Surveys report that in the setting of a poor preparation, endoscopists' recommendations for follow-up evaluation vary and err on shorter return intervals (14, 15). In 1 study 65 board-certified gastroenterologists and 13 gastroenterology fellows (14) were shown images of preparations of "excellent to intermediate quality." With a "nearly perfect" preparation, a 10-year interval generally was recommended for a normal screening colonoscopy. However, recommendations were quite variable for the lower-quality preparations, ranging from more than 5 years to an immediate repeat procedure. A survey of gastroenterologists (n=116) preparing for board certification found that 83% would recommend follow-up evaluation in 3 years or less for 1–2 small adenomas and a suboptimal preparation (15) Several studies have examined actual recommendations for follow-up evaluation within the framework of clinical practice. One study abstracted charts from 152 physicians in 55 North Carolina practices on 125 consecutive persons in each practice (16) Preparation quality was not reported in 32% of the examinations. Bowel preparations rated less than excellent were associated with more aggressive surveillance for those found with no polyps or small and/or medium adenomas. A prospective single-center study of 296 patients showed that when endoscopists encountered a poor preparation they recommended follow-up intervals that more often were nonadherent with guidelines (34% nonadherent vs. 20% adherent; P=.01) (17) A prospective study estimated that for each 1% of bowel preparations deemed inadequate and requiring repeat colonoscopy at a shortened interval, the costs of delivering colonoscopy overall were increased by 1% (5) These substantial adverse effects of inadequate preparation are the rationale for establishing a target for rates of adequate preparation (see later). Dosing and timing of colon cleansing regimens Recommendations Use of a split-dose bowel cleansing regimen is strongly recommended for elective colonoscopy (Strong recommendation, high-quality evidence). A same-day regimen is an acceptable alternative to split dosing, especially for patients undergoing an afternoon examination (Strong recommendation, high-quality evidence). The second dose of split preparation ideally should begin 4–6 h before the time of colonoscopy with completion of the last dose at least 2 h before the procedure time (Strong recommendation, moderate-quality evidence). Split-dose regimens When preparation agents are administered entirely the day before colonoscopy, chyme from the small intestine enters the colon and accumulates, producing a film that coats the proximal colon and impairs detection of flat lesions. The length of time between the last dose of preparation and the initiation of colonoscopy correlates with the quality of the proximal colon cleansing (18, 19, 20) In 1 study the chance of good or excellent preparation of the right colon decreased by up to 10% for each additional hour between the end of ingesting the preparation and the start of the colonoscopy (20) "Splitting" implies that roughly half of the bowel cleansing dose is given on the day of the colonoscopy. Overwhelmingly consistent data show superior efficacy with a split dose compared with the traditional regimen of administering the preparation the day before the procedure (18, 21, 22, 23, 24) Split dosing leads to higher ADRs (25, 26). Four guidelines have endorsed split dosing of preparations for colonoscopy (27, 28, 29, 30) Same-day regimens Same-day bowel cleansing is an effective alternative to split dosing for patients with an afternoon colonoscopy (31, 32, 33, 34) In a large, single-blind, prospective study, same-day preparation provided better mucosal cleansing, less sleep disturbance, better tolerance, less impact on activities of daily living, and greater patient preference scores compared with split dosing (35) Obstacles to split and same-day regimens Anecdotally, anesthesia providers sometimes oppose split and same-day dosing because of concern for aspiration risk. An evidenced-based guideline from the American Society of Anesthesiologists, however, states that ingestion of clear liquids until 2 h before sedation does not affect residual gastric volume (36) Furthermore, 2 endoscopic studies found that ingestion of bowel cleansing agents on the day of colonoscopy did not affect residual gastric volumes, indicating that the rate of gastric emptying of bowel preparations is similar to other clear liquids (37, 38) Preoperative dehydration may be a greater safety concern than drinking clear liquids before anesthesia. A second objection to split dosing is that patients scheduled for early morning procedures may be unwilling to get up during the night to take the second dose of laxatives. Acceptance of and compliance with split-dose bowel preparation is high and should not pose a deterrent to prescribing split-dose preparations for colonoscopy (39, 40) The risk of fecal incontinence during transit to the endoscopy center is increased only minimally with split dosing (40) Diet during bowel cleansing Recommendation By using a split-dose bowel cleansing regimen, diet recommendations can include either low-residue or full liquids until the evening on the day before colonoscopy (Weak recommendation, moderate-quality evidence). Traditionally, patients are instructed to ingest only clear liquids the day before colonoscopy. Recent randomized trials report that a liberalized diet the day before colonoscopy is associated with better tolerance of the preparation and comparable or better bowel cleansing (41, 42, 43, 44, 45, 46, 47, 48). The diet regimens in these trials were variable and included a regular diet until 6 PM, regular breakfast, low-residue breakfast, lunch and snack, a soft diet, and a semiliquid diet (heterogeneity: P=.008; I=62%). With this degree of heterogeneity we are reluctant to recommend a regular diet the day before colonoscopy. Accordingly, a low-residue diet for part or all of the day before colonoscopy can be considered for patients without other identifiable preprocedural risks for inadequate colon preparation. Pending additional study, colonoscopists carefully should evaluate any compromise in efficacy if dietary flexibility is allowed. Usefulness of patient education and navigators for optimizing preparation results Recommendations Health care professionals should provide both oral and written patient education instructions for all components of the colonoscopy preparation and emphasize the importance of compliance (Strong recommendation, moderate-quality evidence). The physician performing the colonoscopy should ensure that appropriate support and process measures are in place for patients to achieve adequate colonoscopy preparation quality (Strong recommendation, low-quality evidence). A patient education program administered by health care professionals increases patient compliance, improves quality, and decreases repeat examinations and costs (49) The use of both verbal and written instructions, compared with written instructions only, is an independent predictor of adequate bowel preparation quality. Educational tools such as booklets, information leaflets, animations, and visual aids should be standardized and validated, (50, 51), and should be effective across a range of health literacy and education levels (4, 52) The use of a novel patient educational booklet on precolonoscopy preparation resulted in better bowel preparation quality scores than those achieved using conventional instructions (OR, 3.7; 95% CI, 2.3–5.8) (53) Trained patient navigators help guide patients through the colonoscopy process. They provide education to patients, address barriers to colonoscopy, review bowel preparation protocols and appointments, and ensure that patients have an escort for appointments. Patient navigators for urban minorities in open-access referral systems resulted in an increase for screening colonoscopy completion rates (54, 55). In safety-net hospitals the costs of navigation are offset by increased screening compliance and navigation is cost effective (56) Barriers to successful navigation included incomplete contact information, language problems, and insurance lapses. The impact of the sex, ethnicity, and professional status of the patient navigator needs additional evaluation. Rating the quality of bowel preparation during colonoscopy Recommendations Adequacy of bowel preparation should be assessed after all appropriate efforts to clear residual debris have been completed (Strong recommendation, low-quality evidence). Measurement of the rate of adequate colon cleansing should be conducted routinely (Strong recommendation, moderate-quality evidence). Adequate preparation, defined as cleansing that allows a recommendation of a screening or surveillance interval appropriate to the findings of the examination, should be achieved in 85% or more of all examinations on a per-physician basis (Strong recommendation, low-quality evidence). Reporting the quality of the bowel preparation is a required element of the colonoscopy report (57, 58) In clinical trials cleansing quality often is estimated using scales that downgrade quality for retained fluid. In clinical practice, however, retained fluid and much of the semisolid debris in the colon can be removed by intraprocedural cleansing. Because the capacity to conduct effective mucosal inspection is established after intraprocedural cleansing, the preparation quality in clinical practice should be assessed only after appropriate intraprocedural washing and suctioning has been completed. For this reason, the use of a validated bowel preparation scale that includes scoring retained fluid (eg, Aronchick, Ottawa) is not recommended. The US Multi-Society Task Force (USMSTF) considers the operational definition of an adequate preparation is one in which the colonoscopist can and does recommend a follow-up screening or surveillance interval for the next colonoscopy that is appropriate for the examination findings. Unfortunately, the scores in validated scales that correspond to the point at which the preparation meets the USMSTF operational definition of an adequate preparation (ability to follow the recommended screening or surveillance interval) generally are uncertain. In clinical practice clinicians often use an imprecisely defined 4-point scale of excellent, good, fair, and poor. In this scheme, excellent and good are widely viewed as adequate, but some research indicates that many fair preparations in clinical practice also are adequate (10) The USMSTF previously recommended that clinicians could consider the preparation adequate if after suctioning and washing the mucosa during the procedure it was deemed adequate for the detection of lesions greater than 5 mm in size (59) This concept is not part of a validated bowel preparation scale but it does reflect current concepts about the sizes of colorectal lesions that are clinically most important to detect (60) Additional research is needed to develop validated scales for scoring bowel cleansing that do not consider retained fluid and include defined points that correspond to adequate preparation. Currently, the Boston Bowel Preparation scale comes closest to meeting these criteria because it does not consider retained fluid and a Boston Bowel Preparation Scale score of 5 or higher was associated with only a 2% rate of recommending shortened follow-up intervals (61) A detailed review of bowel preparation scales is shown in Appendix B. Whichever scale is used in practice, we recommend that the method for defining an adequate preparation should include whether the colonoscopist recommends the expected screening or surveillance intervals based on the colonoscopy findings, and that the ability to detect lesions greater than 5 mm in size throughout the colon is a clinically relevant test of adequacy and appropriateness to follow screening and surveillance intervals. Furthermore, endoscopists are encouraged to submit procedure reports into a data registry that benchmarks performance and quality measures against minimally accepted national thresholds and mean levels of performance among peers. If the rate of adequate bowel preparation for an endoscopist is below the USMSTF recommended benchmark of 85%, an improvement initiative should be undertaken. High rates of inadequate preparations can reflect low patient compliance, failure to adjust preparation regimens for medical predictors of inadequate preparation, or signal that processes and policies of the endoscopy unit need revision. FDA-approved preparations Recommendations Selection of a bowel-cleansing regimen should take into consideration the patient's medical history, medications, and, when available, the adequacy of bowel preparation reported from prior colonoscopies (Strong recommendation, moderate-quality evidence). A split-dose regimen of 4 l PEG-ELS provides high-quality bowel cleansing (Strong recommendation, high-quality evidence). In healthy nonconstipated individuals, a 4-L PEG-ELS formulation produces a bowel-cleansing quality that is not superior to a lower-volume PEG formulation (Strong recommendation, high-quality evidence). Polyethylene glycol–electrolyte lavage solution (PEG-ELS)–based cleansing agents are available in 4 L (considered large or high volume) or as 2 L plus an adjunct (considered low volume). Sodium phosphate (NaP) solution (Fleet Phospho-Soda and Fleet EZ-PREP; C.B. Fleet Co, Lynchburg, VA) is a hyperosmotic cleansing agent that was withdrawn from the US over-the-counter (OTC) market in December 2008 because of concern regarding phosphate-induced renal disease (62) A prescription tablet formulation of NaP (OsmoPrep; Salix Pharmaceuticals, Raleigh, NC) remains available, although a boxed warning about the risk of acute phosphate nephropathy has been added to the label (62) Recently approved low-volume agents include oral sulfate solution (OSS) (SUPREP; Braintree Laboratories, Braintree, MA), sodium picosulfate/magnesium citrate (Prepopik; Ferring Pharmaceuticals, Inc, Parsippany, NJ), and a combination of PEG-ELS and OSS (SUCLEAR; Braintree Laboratories). Polyethylene glycol–electrolyte lavage solution Reduced-volume, FDA-approved PEG-ELS formulations were developed to improve tolerance. One of these preparations (2-L PEG-ELS with bisacodyl, HalfLytely; Braintree Laboratories), recently was removed from the market. Another 2-L PEG-ELS product contains supplemental ascorbate and sodium sulfate (MoviPrep; Salix Pharmaceuticals). Several 4-L PEG-ELS–based preparations have been approved by the FDA, including Colyte (Alaven Pharmaceuticals, Marietta, GA), Gavilyte (Gavis Pharmaceuticals, Somerset, NJ), Golytely (Braintree Laboratories), and Nulytely (Braintree Laboratories), which is sulfate free. High-volume PEG-ELS (≥3 L) was compared with low-volume PEG-ELS (<3 L) in 28 trials yielding 7208 intention-to-treat (ITT) patients (3456 high-volume PEG-ELS; 3752 low-volume PEG-ELS) (18, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89) Twenty-one trials included analyzable bowel-cleanliness outcomes (64, 65, 66, 67, 68, 69, 70, 71, 72, 74, 75, 76, 79, 81, 82, 83, 84, 85, 86, 88, 89) High-volume PEG-ELS did not show a significant increase in bowel cleanliness (OR, 1.03; 95% CI, 0.80–1.32). Eight trials included a PEG-ELS split dose in which 2 L were administered the day before and 2 L were administered the day of the procedure compared with a PEG-ELS nonsplit regimen regardless of dosage, yielding 1990 ITT patients (846 PEG-ELS split [2 L+2 L] dose; 1144 PEG nonsplit) (18, 46, 66, 81, 84, 85, 90, 91) Six trials were analyzable, resulting in significantly increased cleanliness for the PEG-ELS split-dose regimen (2 L+2 L) compared with the PEG-ELS nonsplit dose (OR, 4.38; 95% CI, 1.88–10.21) (46, 66, 81, 84, 85, 90) Because they are iso-osmotic, PEG-ELS regimens often are considered preferred regimens in patients who are less likely to tolerate fluid shifts, including patients with renal insufficiency, congestive heart failure, and advanced liver disease. Oral sulfate solution Two trials evaluated OSS (92, 93). One trial compared OSS in a split-dose regimen with 4 l PEG-ELS taken the day before and found more successful preparations with OSS (98.4% vs. 89.6%; P <.04, per-protocol data) (93) The second trial compared OSS with PEG-ELS 2 L plus ascorbate. Both OSS and 2 L PEG-ELS plus ascorbate were more effective when given in split doses, and the FDA approved OSS for split-dose administration only (92) The combined results of 923 ITT patients (462 OSS, 461 PEG) found that OSS did not increase bowel cleanliness (OR, 1.12; 95% CI, 0.77–1.62) (92, 93). Sodium picosulfate Sodium picosulfate (PICO), a stimulant laxative often combined with a magnesium salt, recently was introduced to the US market after considerable experience in Canada, Europe, and Australia. Eleven trials compared PICO vs. PEG-ELS and yielded 3097 ITT patients (1385 PICO, 1715 PEG-ELS) (77, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103) The PICO preparations were combined either with magnesium oxide or magnesium citrate. Ten trials included analyzable cleanliness data comparing PICO with PEG-ELS (94, 95, 96, 97, 98, 99, 100, 101, 102, 103) The PICO formulation did not show a significant increase in efficacy compared with PEG-ELS (OR, 0.92; 95% CI, 0.63–1.36). Eight trials compared PICO with NaP, yielding 1792 ITT patients (966 PICO, 826 NaP) (77, 97, 104, 105, 106, 107, 108, 109) Three trials included analyzable cleanliness data, PICO was not superior to NaP (OR, 0.60; 95% CI, 0.22–1.65) (97, 106, 107) Only 1 trial compared the PICO split-dose regimen vs PICO the day before or the same day including 250 ITT patients (127 split, 123 not split) (110). PICO split-dose compared with PICO day-before or same-day regimen had a significantly higher proportion of bowel cleanliness (OR, 3.54; 95% CI, 1.95–6.45). Sodium phosphate Oral NaP use for bowel preparation has decreased because of the rare occurrence of renal damage from tubular deposition of calcium phosphate (111, 112) Potential risk factors for NaP-induced nephropathy include the following: female sex, pre-existing renal insufficiency, inadequate hydration during bowel preparation, reduced time interval between the 2 doses of sodium phosphate (<12 h), hypertension, older age, and certain medications (diuretics, nonsteroidal anti-inflammatory drugs, and renin-angiotensin inhibitors) (113). Forty-eight trials were included in a comparison of NaP vs PEG-ELS, yielding 11,368 ITT patients (5529 PEG vs. 5839 NaP) (75, 76, 77, 97, 108, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157) Thirty-three trials included analyzable bowel-cleanliness outcomes (75, 76, 97, 108, 114, 115, 117, 119, 121, 124, 126, 127, 129, 130, 131, 132, 133, 136, 137, 139, 140, 141, 143, 145, 146, 148, 150, 151, 152, 153, 154, 155, 156) The use of NaP did not show an increase in bowel cleanliness (OR, 1.02; 95% CI, 0.77–1.36) but was associated with better willingness to repeat the regimen (OR, 2.61; 95% CI, 1.48–4.59). Comparisons of NaP with OSS and PICO were discussed previously. Three trials (144, 158, 159) were included in the comparison of the NaP split-dose regimen with NaP the day before the procedure or the same day for a total of 598 ITT patients (355 split vs. 243 nonsplit) (144, 158, 159) Two trials(158, 159) included analyzable data and showed better cleansing with split-dose regimens (OR, 2.35; 95% CI, 1.27–4.34) (158, 159) Although NaP is effective and well tolerated by most patients, the risk of adverse events makes it unsuitable as a first-line agent. Furthermore, NaP is not recommended in patients with renal insufficiency (creatinine clearance,<60 mL/min/1.73 m2), pre-existing electrolyte disturbances, congestive heart failure (New York Heart Association class III or IV or ejection fraction<50%), cirrhosis, or ascites. Caution should be used in prescribing NaP to patients who are elderly, hypertensive, or taking angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or diuretics. OTC Non–FDA-approved preparations Recommendations The OTC bowel cleansing agents have variable efficacy that ranges from adequate to superior, depending on the agent, dose, timing of administration, and whether it is used alone or in combination; regardless of the agent, the efficacy and tolerability are enhanced with a split-dose regimen (Strong recommendation, moderate-quality evidence). Although the OTC purgatives generally are safe, caution is required when using these agents in certain populations; for example, magnesium-based preparations (both OTC and FDA-approved formulations) should be avoided in patients with chronic kidney disease (Weak recommendation, very low quality evidence). The use of OTC products for bowel cleansing before colonoscopy is deemed to be safe for use by the public without advice from a health care professional. The efficacy and safety of these products for specific indications may be unproven because the FDA's oversight of OTC products generally is conducted by therapeutic class rather than for individual drugs. Consequently, an OTC product may have little or no supporting evidence or comparative data showing either efficacy or safety relative to other available products. Products marketed specifically for colonoscopy bowel preparation must be evaluated in randomized trials to assess their efficacy and safety and then must receive approval via a New Drug Application (NDA) from the FDA. Such products are available only by prescription. For a purgative agent to be marketed without an approved NDA it must meet the requirements for OTC agents as set forth in the Laxative Monograph (Unpublished data). The FDA specifically recognized only 2 bowel cleansing kits (160) and any kit with different components would require an approved NDA and/or further amendment to the monograph (highly unlikely). These cleaning kits are as follows: magnesiu
Referência(s)