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Background Data on treatment satisfaction in European men and women with chronic constipation are limited. Aim To assess satisfaction with current treatment among European men and women with chronic constipation. Methods An internet-based survey was conducted in 2009 in 10 European countries: Austria, Germany, France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands. Participants had self-reported chronic constipation (<3 bowel movements/week and ≥1 symptoms for ≥6 months of: pain during defecation; lumpy/hard faeces; and feeling of incomplete evacuation). Demographic data and disease history were collected. For participants using laxatives, drug name/class, satisfaction with treatment and interest in other treatments were collected. Results Of the 1941 participants screened, 1355 had chronic constipation and met the inclusion criteria (chronic constipation population). The majority of the chronic constipation population who disclosed their sex ( n = 811) were women (82%). Sixty-eight per cent of respondents ( n = 855/1255) reported using laxatives, with the proportion of laxative users differing between subsets. Twenty-eight per cent ( n = 225/793) were (very) satisfied with their treatment, whereas 44% ( n = 345/793) were neutral and 28% ( n = 223/793) (very) dissatisfied. There was no relationship between type of laxative and degree of (dis)satisfaction. Interest in other treatments was high with 83% ( n = 686/827) of respondents 'absolutely' or 'probably' interested. Respondents dissatisfied with their treatment were more likely to be interested in other treatments. Conclusions Laxative-use is common for chronic constipation. In this large survey, 28% of participants were dissatisfied with their treatment, with the majority interested in other treatments. [ABSTRACT FROM AUTHOR]

Summary Background The nonselective 5- HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events ( AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5- HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5- HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5- HT4 agonists had reports of cardiovascular AEs: cisapride ( QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5- HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5- HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5- HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5- HT4 agonists for GI disorders differ in chemical structure and selectivity for 5- HT4 receptors. Selectivity for 5- HT4 over non-5- HT4 receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5- HT4 agonists may offer improved safety to treat patients with impaired GI motility. [ABSTRACT FROM AUTHOR]

The discusses a study of the pathophysiology, diagnosis, management and available guidelines for the treatment of chronic constipation in Europe. The authors described the three categories of primary constipation, namely, normal-transit, slow-transit and pelvic floor dysfunction. They also examined the effectiveness of drugs that are commonly used in treating constipation such as stimulant laxatives and dietary fibers.

Background Constipation affects up to 50% of the elderly; this study evaluates the efficacy, safety, and tolerability of the selective 5-HT4 agonist prucalopride in chronically constipated elderly patients. Methods Three hundred chronic constipation patients aged ≥65 years were randomized to prucalopride (1, 2, or 4 mg once daily) or placebo for 4 weeks. The primary endpoint was the percentage of patients with ≥3 spontaneous complete bowel movements (SCBM) per week. Secondary endpoints included the percentage with an increase of ≥1 SCBM per week, BM frequency, constipation-related symptoms, quality of life (QoL), safety, and tolerability. Key Results More patients achieved ≥3 SCBM per week with prucalopride than with placebo. This difference was largest and significant during the first week of 4 mg prucalopride ( P ≤ 0.05). Significantly more patients in each prucalopride group achieved an increase of ≥1 SCBM per week from baseline vs placebo (e.g. 60% with 1 mg prucalopride vs 34% with placebo at week 4; P ≤ 0.05). More patients had improvement in PAC-QOL satisfaction score of ≥1 with 1 mg prucalopride than with placebo ( P ≤ 0.05); the same was true for PAC-SYM stool symptoms (1 and 4 mg prucalopride; P ≤ 0.05). Treatment-emergent adverse events were similar between groups: the most frequently reported with prucalopride were headache and gastrointestinal events. There were no clinically significant differences between prucalopride and placebo for vital signs, laboratory assessments, or ECG variables. Conclusions & Inferences Prucalopride, in the dose-range tested (1–4 mg once daily), has beneficial effects on bowel movements, symptoms, and QoL, and is safe and well-tolerated in elderly patients with chronic constipation. [ABSTRACT FROM AUTHOR]

Therapy trials with bacterial compounds in irritable bowel syndrome (IBS) have produced conflicting results. This study was performed in 1988 and 1989, and was re-analysed according to current IBS standards. Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor® (Symbiopharm GmbH, Herborn, Germany), an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli, or placebo in a double-blinded, randomized fashion. Patients were seen weekly by the physician, who assessed the presence of core IBS symptoms. Responders had at least a 50% decrease in global symptom score (GSS) and in abdominal pain score (APS) reports at ≥1 visit during treatment. The responder rate in GSS to the drug was 102/149 (68.5%) in comparison to placebo with 56/148 (37.8%) ( P < 0.001), the improvement in APS was 108/149 (72.5%) and 66/148 (44.6%) respectively ( P = 0.001). The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report. Kaplan–Meier analysis revealed a mean response time of 4–5 weeks for active treatment and more than 8 weeks for placebo ( P < 0.0001). Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners. [ABSTRACT FROM AUTHOR]

: Symptoms of irritable bowel syndrome are often cyclical and thus may require repeated rather than continuous therapy. Tegaserod is effective and well-tolerated for irritable bowel syndrome with constipation but data on retreatment are lacking.: To assess whether tegaserod retreatment is as efficacious and well-tolerated as initial treatment in a primary care setting.: This open-label trial was designed to evaluate the effectiveness of tegaserod under real-life conditions. Irritable bowel syndrome with constipation patients received tegaserod 6 mg b.d. for 12 weeks; response was assessed at weeks 4 and 12. Responders (those achieving satisfactory relief for at least 2 of the previous 4 weeks) at weeks 4 and/or 12 entered an 8-week withdrawal period where symptom recurrence was assessed. Patients experiencing recurrence could receive tegaserod 6 mg b.d. for another 4 weeks (retreatment phase) and on completion, could choose to continue tegaserod in a 6-month extension study.: A total of 513 patients received initial treatment with tegaserod; 85.0% (436 of 513) responded. 403 responders entered the withdrawal period; symptoms recurred in 83.9% (338 of 403) after a mean of 38 days. Of the 307 patients who subsequently entered retreatment 89.3% (274 of 307) responded. Among patients entering the retreatment period, 269 (87.6%) had responded within the first 4 weeks of initial treatment. Of these, 243 (90.3%) responded to tegaserod retreatment. Adverse events were infrequent and similar during 4 weeks of the initial treatment period (11.1%) and on retreatment (10.4%). The extension study, completed by 188 of 232 (81.0%) patients, demonstrated good long-term tolerability of tegaserod.: Irritable bowel syndrome with constipation patients can be successfully treated, and retreated, with tegaserod 6 mg b.d. Tegaserod was well-tolerated during initial and retreatment periods. [ABSTRACT FROM AUTHOR]

Summary Background : Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. Aims : To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. Results : The panel recommended antacids ‘on-demand’ as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. Conclusions : The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine. [ABSTRACT FROM AUTHOR]

Aim:To investigate the efficacy and safety of tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods:Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results:Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo. Conclusions:Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated. [ABSTRACT FROM AUTHOR]

Background: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs)., Aim: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy., Methods: Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data., Results: Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride)., Conclusions: 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility., (© 2012 Blackwell Publishing Ltd.)

Aim: To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study., Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks., Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo., Conclusions: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.