Bisacodyl in the Acute Treatment of Constipation
Background: Although laxatives are a first-line treatment for constipation, there are few randomized placebo-controlled trials assessing their efficacy.
Aim: To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.
Methods: 55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3-day run-in period. Patients recorded stool frequency and consistency and adverse events.
Results: In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl-treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from 'hard' (run-in) to between 'soft' and 'well-formed' during bisacodyl treatment, remaining between 'moderately hard' and 'hard' for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.
Conclusions: Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.
Chronic, idiopathic constipation, described as decreased bowel frequency or the excessive need to strain during defecation, affects up to 28% of the population in developed countries. It has a significant impact on quality of life and represents a considerable burden on healthcare systems. It is a particular issue in the elderly. In the United Kingdom, it is estimated that 3 million general practitioner consultations per year relate to constipation. Modifications to diet, including an increase in fibre-containing foods, can bring benefit to certain patients but, often, additional medical treatment is required. Of the alternatives available, laxatives are a preferred first-line treatment, given a general acceptance of their rapid onset of action (especially the stimulant laxatives), overall efficacy and safety profiles. Surprisingly, however, there is a relative paucity of reports on formal clinical studies of their efficacy and safety and only very few double-blind, placebo-controlled trials are available. Indeed, Ramkumar and Rao have concluded recently that there are very few laxative preparations for which there are sufficient clinical trials data to support or reject their use in the treatment of constipation.
Bisacodyl [4,4'-diacetoxy-diphenyl-(pyridyl-2)-methane] has been used as a first-line laxative throughout the world for many years. Clinical experience suggests that it is highly effective, yet only few controlled studies are available that examine its efficacy. Bisacodyl is a prokinetic with a hydrogogue effect, a contact laxative, which acts locally in the large bowel by directly enhancing motility, reducing transit time and increasing the water content of the stool. Its delivery is therefore targeted at this part of the gastrointestinal tract. Administered as a sugar-coated formulation, bisacodyl is resistant to cleavage in the stomach and small intestine, and is therefore delivered to the colon essentially intact. Deacetylation of bisacodyl, under the influence of endogenous enzymes in the colon, leads to formation of the active diphenol; the time to onset of action (stimulation of colonic peristaltic activity) being approximately 6–12 h after oral administration.
As is the case for all laxatives that have been in use for a long time, most published studies on the efficacy of bisacodyl are of uncontrolled design, with a few exceptions of randomized-controlled studies. Nevertheless, there is general acceptance of the efficacy of bisacodyl and it is used frequently as the rescue medication in studies of other agents being tested for their effect in patients with constipation.
The 'Rome II Committee' has developed guidelines with regard to diagnostic criteria for functional bowel disorders and the conduct of clinical trials to evaluate new treatments and these have often been adopted, particularly for registration studies with new drugs. However, the diagnostic criteria and some aspects of the recommendations for study design within these guidelines do not necessarily reflect normal clinical practice. For example, laxatives are often used in the short-term for acute intermittent constipation; the benefit of laxatives used in the short-term needs to be established.
The aim of the present randomized-controlled study was to establish the efficacy and safety of once daily treatment for 3 days with bisacodyl tablets vs. placebo in adult patients with a history of constipation, and presenting with an acute episode. The study was intended to reflect the situation in a general practice setting, where patients present, not infrequently, requiring short-term or intermittent therapy.
Summary and Introduction
Summary
Background: Although laxatives are a first-line treatment for constipation, there are few randomized placebo-controlled trials assessing their efficacy.
Aim: To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.
Methods: 55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3-day run-in period. Patients recorded stool frequency and consistency and adverse events.
Results: In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl-treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from 'hard' (run-in) to between 'soft' and 'well-formed' during bisacodyl treatment, remaining between 'moderately hard' and 'hard' for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.
Conclusions: Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.
Introduction
Chronic, idiopathic constipation, described as decreased bowel frequency or the excessive need to strain during defecation, affects up to 28% of the population in developed countries. It has a significant impact on quality of life and represents a considerable burden on healthcare systems. It is a particular issue in the elderly. In the United Kingdom, it is estimated that 3 million general practitioner consultations per year relate to constipation. Modifications to diet, including an increase in fibre-containing foods, can bring benefit to certain patients but, often, additional medical treatment is required. Of the alternatives available, laxatives are a preferred first-line treatment, given a general acceptance of their rapid onset of action (especially the stimulant laxatives), overall efficacy and safety profiles. Surprisingly, however, there is a relative paucity of reports on formal clinical studies of their efficacy and safety and only very few double-blind, placebo-controlled trials are available. Indeed, Ramkumar and Rao have concluded recently that there are very few laxative preparations for which there are sufficient clinical trials data to support or reject their use in the treatment of constipation.
Bisacodyl [4,4'-diacetoxy-diphenyl-(pyridyl-2)-methane] has been used as a first-line laxative throughout the world for many years. Clinical experience suggests that it is highly effective, yet only few controlled studies are available that examine its efficacy. Bisacodyl is a prokinetic with a hydrogogue effect, a contact laxative, which acts locally in the large bowel by directly enhancing motility, reducing transit time and increasing the water content of the stool. Its delivery is therefore targeted at this part of the gastrointestinal tract. Administered as a sugar-coated formulation, bisacodyl is resistant to cleavage in the stomach and small intestine, and is therefore delivered to the colon essentially intact. Deacetylation of bisacodyl, under the influence of endogenous enzymes in the colon, leads to formation of the active diphenol; the time to onset of action (stimulation of colonic peristaltic activity) being approximately 6–12 h after oral administration.
As is the case for all laxatives that have been in use for a long time, most published studies on the efficacy of bisacodyl are of uncontrolled design, with a few exceptions of randomized-controlled studies. Nevertheless, there is general acceptance of the efficacy of bisacodyl and it is used frequently as the rescue medication in studies of other agents being tested for their effect in patients with constipation.
The 'Rome II Committee' has developed guidelines with regard to diagnostic criteria for functional bowel disorders and the conduct of clinical trials to evaluate new treatments and these have often been adopted, particularly for registration studies with new drugs. However, the diagnostic criteria and some aspects of the recommendations for study design within these guidelines do not necessarily reflect normal clinical practice. For example, laxatives are often used in the short-term for acute intermittent constipation; the benefit of laxatives used in the short-term needs to be established.
The aim of the present randomized-controlled study was to establish the efficacy and safety of once daily treatment for 3 days with bisacodyl tablets vs. placebo in adult patients with a history of constipation, and presenting with an acute episode. The study was intended to reflect the situation in a general practice setting, where patients present, not infrequently, requiring short-term or intermittent therapy.
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