tegaserod and Constipation

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common gastrointestinal disorders imposing considerable impact on the quality of life and well-being of affected individuals. A paucity of evidence-based treatment options exist for CIC and IBS-C sufferers. Tegaserod, a 5-HT

Topics: Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Quality of Life; Serotonin; Serotonin Receptor Agonists

Tegaserod is a 5-HT. An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (tegaserod: n = 20; placebo: n = 4) identified internally. A second independent external adjudication further evaluated these events.. A total of 18,645 patients were included (tegaserod: n = 11,614; placebo: n = 7031). The first adjudication identified 14 (0.075%) events (tegaserod: n = 13 [0.11%]; placebo: n = 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52-34.74; P = .273). All tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women <65 years of age without a history of cardiovascular ischemic events and ≤1 cardiovascular risk factor receiving tegaserod experienced no major adverse cardiovascular event(s).. Two independent, external adjudications suggest that tegaserod is safe for women <65 years of age with irritable bowel syndrome with constipation, no history of cardiovascular ischemic events, and ≤1 cardiovascular risk factor.

Topics: Adult; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome

Tegaserod was the first US Food and Drug Administration-approved drug for irritable bowel syndrome with constipation (IBS-C) in women and was recently reapproved for use. Recognizing that clinical trials were performed almost 20 years ago, we performed an integrated analysis on patient-reported outcomes relevant to current practice including previously unpublished data.. Data from 4 12-week, randomized, placebo-controlled trials evaluating tegaserod 6 mg b.i.d. in patients with IBS-C were pooled. We analyzed 2 groups: all women (overall population) and women younger than 65 years without a history of cardiovascular ischemic events (indicated population). The primary end point was subjective global assessment of IBS-C symptom relief. Responders rated themselves as "considerably" or "completely" relieved ≥50% of the time or at least "somewhat relieved" 100% of the time over the last 4 weeks.. The overall and indicated populations included 2,939 (tegaserod [n = 1,478]; placebo [n = 1,461]) and 2,752 (tegaserod [n = 1,386]; placebo [n = 1,366]) participants, respectively. The pooled odds ratios (95% confidence interval) for clinical response during the last 4 weeks in the overall and indicated populations with tegaserod were 1.37 (1.18, 1.59; P < 0.001) and 1.38 (1.18, 1.61; P < 0.001). In the overall and indicated populations, clinical response rates for tegaserod during the last 4 weeks were 43.3% and 44.1% versus 35.9% and 36.5% with placebo (P < 0.001). Adverse events were similar between groups. No significant cardiovascular events related to tegaserod were observed in patients with ≤1 cardiac risk factor.. Tegaserod 6 mg b.i.d. reduced IBS-C symptoms in overall and US Food and Drug Administration-indicated populations (women aged <65 years with no history of cardiovascular ischemic events).

Topics: Adult; Constipation; Female; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder affecting 1 in 10 people and associated with poor psychological health, reduced quality of life, and increased health care expenditure.

Topics: Constipation; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Network Meta-Analysis; Treatment Outcome

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.

Topics: Alprostadil; Bile Acids and Salts; Chloride Channels; Chronic Disease; Constipation; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Organic Anion Transporters, Sodium-Dependent; Peptides; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists; Serotonin Agents; Symporters

Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (C-IBS) are commonly reported gastrointestinal (GI) disorders that have a major impact on health and quality of life. Patients experience a range of symptoms of which infrequency of bowel movement is but one and report that straining, the production of hard stools, and unproductive urges are more bothersome than stool infrequency. Additionally, in C-IBS, patients report abdominal pain and bloating as particularly troubling. Traditional treatments, such as laxatives, are often ineffective, especially in more severe constipation over the long term. In a population-based survey of constipation sufferers, half were not satisfied with their current treatment, due predominantly to poor efficacy. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists stimulate GI motility and intestinal secretion, and tegaserod has demonstrated efficacy in improving bowel habit. Tegaserod also improves constipation-associated symptoms including bloating, abdominal discomfort, stool consistency, and straining in patients with both CIC and C-IBS. However, tegaserod has been withdrawn due to an association with serious adverse cardiovascular effects. Further 5-HT(4) receptor agonists, including prucalopride and TD-5108 are in development and show exciting results in clinical studies in CIC patients, suggesting further product approvals are likely. Headache and diarrhea are the most commonly reported adverse event with this class of agent. Recently a novel prosecretory agent has been approved for the treatment of both CIC and C-IBS. Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea, diarrhea, and headache are the most commonly reported adverse events. Linaclotide also stimulates intestinal chloride secretion, but this molecule achieves this indirectly, through the activation of guanylate cyclase C. Data are emerging, but the efficacy and safety profile of this agent in the treatment of CIC and C-IBS appears encouraging.

Topics: Alprostadil; Azabicyclo Compounds; Benzofurans; Chloride Channels; Chronic Disease; Constipation; Gastrointestinal Agents; Gastrointestinal Motility; Guanylate Cyclase; Humans; Indoles; Irritable Bowel Syndrome; Laxatives; Lubiprostone; Peptides; Safety; Serotonin 5-HT4 Receptor Agonists; Serotonin Receptor Agonists; Treatment Outcome

Topics: Adult; Alprostadil; Chronic Disease; Constipation; Dietary Fiber; Female; Gastrointestinal Transit; Humans; Indoles; Laxatives; Life Style; Lubiprostone; Male; Serotonin Receptor Agonists

To evaluate data that address the safety and efficacy of tegaserod for the management of chronic constipation (CC) in elderly patients.. Primary literature was identified through MEDLINE (1966-January 2007) and EMBASE (2002-January 2007) using the search terms tegaserod, elderly, and constipation. Additional information was requested from the pharmaceutical manufacturer.. Clinical trials evaluating the efficacy and safety of tegaserod for treating CC were considered for inclusion. Emphasis was placed on data relevant to use of tegaserod in the elderly and on CC.. Two efficacy trials evaluated tegaserod for treating constipation. They enrolled a total of 331 elderly patients, comprising approximately 13% of study patients. Tegaserod was effective for improving constipation in the overall study populations; no significant adverse events were noted. However, both studies lacked a subgroup analysis in the elderly. Diarrhea occurred more commonly with higher doses of tegaserod and may be a concern in older adults. A 13 month safety trial found tegaserod to be well tolerated for treatment of constipation, with similar adverse events seen as in the 12 week efficacy studies. Specific data were not provided for elderly patients.. Tegaserod should not replace current therapies for treatment of CC in the elderly. The drug has been studied in a small number of older adults; thus, data are inconclusive about its use in this population. Older adults have a higher risk of diarrhea with tegaserod. Cautious use is warranted until further studies specifically address the elderly population.

Topics: Aged; Chronic Disease; Constipation; Gastrointestinal Transit; Humans; Indoles; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Treatment Outcome

Tegaserod, a selective and partial agonist at the 5-hydroxytryptamine (5-HT [serotonin]) receptor subtype 4 (5-HT4), is the only United States Food and Drug Administration-approved drug for the treatment of constipation-predominant irritable bowel syndrome (IBS) in women. The drug's stimulation of 5-HT4 receptors on intestinal enterocytes increases peristaltic activity and fluid secretion into the gut lumen, facilitating stool passage. In addition, affinity of tegaserod for 5-HT4 receptors modulates visceral sensitivity, which helps alleviate abdominal pain associated with constipation-predominant IBS. The drug's pharmacokinetic and pharmacodynamic parameters do not differ significantly with age or sex. Tegaserod safely and effectively relieves overall gastrointestinal symptoms and abdominal discomfort and normalizes bowel habits in patients with constipation-predominant IBS. It is associated with few drug interactions. In clinical studies, tegaserod was well tolerated, and its adverse-effect profile was similar to that of placebo. Severe diarrhea, as well as abdominal pain, flatulence, headache, and nausea, were the most commonly reported events. Patients who experience severe diarrhea should discontinue the drug. With the data available, tegaserod remains an option for patients with constipation-predominant IBS.

Topics: Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Serotonin 5-HT4 Receptor Agonists; Serotonin Receptor Agonists; Treatment Outcome

Constipation is a worldwide problem that affects many children. Treatment of constipation is largely based on clinical experience rather than on evidence-based controlled clinical trials. Stool softeners and cathartic agents in combination with behavioral interventions constitute the programs most commonly used to facilitate painless and frequent defecation. Long-term treatment is needed for most patients, and approximately 30% of children beyond puberty continue to struggle with symptoms of constipation, such as infrequent, painful evacuation of stools and fecal incontinence. Not surprisingly, chronicity of these bowel complaints may cause significant interference with the child's emotional growth and development. Development of new therapeutic strategies is necessary in order to treat these challenging patients more effectively. This review provides an overview of novel and alternative therapies, such as new drugs, surgery, and probiotics, that are being proposed for the treatment of childhood chronic constipation.

Topics: Acupuncture Therapy; Alprostadil; Botulinum Toxins; Child; Complementary Therapies; Constipation; Electric Stimulation; Fatty Acids; Humans; Indoles; Lubiprostone; Massage; Piperidines; Probiotics; Serotonin Receptor Agonists

Cancer-related constipation is common and a significant detractor from patient quality of life. It has many possible causes and is still not well understood. Information is lacking on therapies for cancer-related constipation among current medications approved by the US Food and Drug Administration (FDA). Most agents have only been formally tested in comparison with placebo in chronic idiopathic constipation if at all. Few comparative studies of laxatives have been performed to establish superiority or synergy. As we understand more about the physiology of the gastrointestinal tract, new targeted therapies have become available. These include a selective chloride channel activator, lubiprostone, and a selective 5HT4 serotonin receptor agonist, tegaserod, both of which have been FDA approved for chronic idiopathic constipation. The role of these agents in cancer-related constipation remains to be seen. On the horizon are two investigational peripherally acting opioid receptor antagonists, alvimopan and methylnaltrexone. Preliminary results in cancer-related constipation suggest that these agents may be important additions to our treatment repertoire.

Topics: Alprostadil; Constipation; Fatty Acids; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Naltrexone; Narcotic Antagonists; Neoplasms; Piperidines; Quaternary Ammonium Compounds; Serotonin Receptor Agonists

The 5-HT(4) partial agonist tegaserod is effective in the treatment of chronic constipation and constipation predominant irritable bowel syndrome. 5-HT(4) receptors are located on presynaptic terminals in the enteric nervous system. Stimulation of 5-HT(4) receptors enhances the release of acetylcholine and calcitonin gene related peptide from stimulated nerve terminals. This action strengthens neurotransmission in prokinetic pathways, enhancing gastrointestinal motility. The knockout of 5-HT(4) receptors in mice not only slows gastrointestinal activity but also, after 1 month of age, increases the age-related loss of enteric neurons and decreases the size of neurons that survive. 5-HT(4) receptor agonists, tegaserod and RS67506, increase numbers of enteric neurons developing from precursor cells and/or surviving in culture; they also increase neurite outgrowth and decrease apoptosis. The 5-HT(4) receptor antagonist, GR113808, blocks all of these effects, which are thus specific and 5-HT(4)-mediated. 5-HT(4) receptor agonists, therefore, are neuroprotective and neurotrophic for enteric neurons. Because the age-related decline in numbers of enteric neurons may contribute to the dysmotilities of the elderly, the possibility that the neuroprotective actions of 5-HT agonists can be utilized to prevent the occurrence or worsening of these conditions should be investigated.

Topics: Animals; Colonic Diseases, Functional; Constipation; Enteric Nervous System; Gastrointestinal Agents; Humans; Indoles; Neurons; Neuroprotective Agents; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin Receptor Agonists; Synapses

IBS is a complex disorder that encompasses a wide profile of symptoms. The symptoms of chronic constipation frequently resemble those of constipation-predominant IBS. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS and chronic constipation.. The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS and chronic constipation in adults and adolescents aged 12 years and above.. MEDLINE 1966-December 2006 and EMBASE 1980 to December 2006 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", "constipation" and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, and the Inflammatory Bowel Disease Review Group Specialized Trials Register were also searched. Searches stopped on 15th December 2006. Relevant articles were retrieved, and their reference lists were also reviewed.. Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS or chronic constipation, focusing on clinical endpoints were considered for review.. Study inclusion and exclusion, data extraction and quality assessment was undertaken by two authors independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistics relative risk for dichotomous data and weighted mean difference for continuous data, both with 95% CI. Thirteen short-term placebo-controlled studies fulfilled the inclusion criteria. These were predominantly conducted in women. Ten studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. Two studies evaluated the effectiveness of tegaserod for the treatment of chronic constipation.. In patients with C-IBS, the relative risk (RR) of being a responder in terms of global relief of GI symptoms during the last 4 weeks of treatment was significantly higher with both tegaserod 12 mg and 4 mg doses compared with placebo. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of three studies were not reached. The responder rate for this endpoint was also higher when considered for the first 4 weeks of treatment (tegaserod 12 mg only). Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in this outcome in favour of tegaserod 12 mg. In patients with chronic constipation, the RR of being a responder in terms of complete spontaneous bowel movements per week with tegaserod 12 mg was 1.54 (95% CI 1.35 to 1.75), WMD for this endpoint compared with placebo 0.6 (95% CI 0.42 to 0.78). Differences between tegaserod and placebo in increases in frequency of bowel movements were small (less than one per week). The proportion of patients with either diagnosis who experienced diarrhea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.80, 95% CI 2.13 to 3.68), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies.. Tegaserod appears to improve the overall symptomatology of IBS, and the frequency of bowel movements in those with chronic constipation. The clinical importance of these modest improvements is not clear. There are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of these conditions.

Topics: Adolescent; Adult; Chronic Disease; Constipation; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Randomized Controlled Trials as Topic

A growing body of evidence implicates abnormal serotonergic regulation of gastrointestinal function in the pathogenesis of the irritable bowel syndrome (IBS). Drugs targeting this system are therefore attractive concepts. The partial 5-HT4 receptor agonist tegaserod might be predicted to have positive therapeutic effects on a constipated and uncomfortable gut. However, IBS runs a chronic, benign course and carries no associated mortality, so it is imperative that the safety profile of new pharmacological agents made available to physicians is exemplary. The authors review the evidence for 5-HT in the aetiology of IBS and its symptoms, and the data available concerning the partial 5-HT4 receptor agonist tegaserod, in terms of rationale, efficacy and safety.

Topics: Biological Availability; Constipation; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Receptors, Serotonin, 5-HT4; Serotonin; Signal Transduction

Increased fiber intake through diet or fiber supplements is an appropriate initial therapy for chronic constipation. Osmotic and stimulant laxatives may be administered to patients who do not respond to more conservative measures if the limitations of these agents are explained. Tegaserod, a selective 5-hydroxytryptamine type 4 (5-HT4) receptor partial agonist, is more effective than placebo at relieving symptoms of chronic idiopathic constipation in patients younger than 65 years of age. Patients with suspected defecation disorders and those with treatment-refractory symptoms should be referred to a gastroenterologist for further evaluation.

Topics: Alprostadil; Cathartics; Chronic Disease; Constipation; Dietary Fiber; Fatty Acids; Gastroenterology; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Referral and Consultation

Symptoms of constipation are commonly seen in medical practice. Once other medical causes have been excluded, distinguishing patients who have constipation-predominant irritable bowel syndrome (IBS) from those with functional constipation has been considered useful in terms of planning management. However, the criteria used to distinguish IBS from functional constipation are arguably arbitrary, and the availability of new therapeutic approaches may render such distinctions of little practical relevance. In this article, the author presents a review of the management implications of differentiating constipation-predominant IBS from functional constipation.

Topics: Biofeedback, Psychology; Cathartics; Constipation; Gastrointestinal Transit; Humans; Indoles; Irritable Bowel Syndrome; Manometry; Pelvic Floor

Topics: Cathartics; Chronic Disease; Constipation; Diagnostic Techniques, Digestive System; Gastrointestinal Agents; Humans; Indoles; Medical History Taking; Physical Examination

Constipation is one of the most common gastrointestinal conditions with limited effective treatment options. Tegaserod, a 5-HT4 receptor agonist has demonstrated efficacy in relieving constipation-related symptoms in patients suffering from irritable bowel syndrome with constipation. This paper reviews two recent reports that have evaluated the efficacy and safety of tegaserod in patients with chronic constipation. Two double-blind, randomized, placebo-controlled trials have been reported; one in Europe and Asia (E2301) the other in North and South America (E2302). After a 2-week baseline period, patients were randomized to treatment with tegaserod 2 mg b.d., tegaserod 6 mg b.d. or placebo for 12 weeks. Two thousand, six hundred and twelve patients were randomized, the majority were white females. In both studies, responder rates during weeks 1-4 were significantly greater in the tegaserod groups compared with placebo. A similar trend was seen over weeks 1-12. Statistically significant improvements over placebo were seen across the majority of secondary efficacy variables. Tegaserod was safe with no consistent differences in the frequency of adverse events among the various groups. In conclusion, treatment of chronic constipation with tegaserod was associated with significant improvement in bowel frequency as well as other constipation symptoms. Tegaserod was also well tolerated in this patient population.

Topics: Aged; Chronic Disease; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists

Studies from the Western hemisphere have established the efficacy and safety of tegaserod in women with irritable bowel syndrome and constipation. This review summarizes the results of recent studies from around the world that confirm the efficacy and safety of tegaserod, and expand our understanding of the role of this drug in the treatment of patients with irritable bowel syndrome.

Topics: Adult; Constipation; Female; Gastrointestinal Agents; Global Health; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists

Gastrointestinal symptoms are the most common side-effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post-US marketing randomized controlled trials. In most patients, tegaserod-induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated and placebo-treated patients. Pooled analysis of Phase III and post-US marketing randomized controlled trials did not demonstrate significant differences between tegaserod-treated and placebo-treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod-using patients in any Phase III or post-marketing randomized controlled trials, and post-marketing surveillance indicated that the rate of ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs. placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although post-US marketing randomized controlled trials did not demonstrate this increase. Other extra-gastrointestinal adverse events occurred with similar frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.

Topics: Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Constipation; Gastrointestinal Agents; Gastrointestinal Diseases; Headache; Humans; Indoles; Irritable Bowel Syndrome; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists

Activation of serotonin 5-HT(4) receptors has been proposed as treatment for irritable bowel syndrome, a common, complex and distressing gastrointestinal disorder. Abnormal intestinal motility and sensitivity in irritable bowel syndrome patients can result in diarrhea, constipation, abdominal pain, bloating, headache and fatigue; these and other symptoms can lead to exacerbation of psychological stress, which may in turn induce further physiological abnormalities and patient discomfort. The serotonin agonist tegaserod binds with high affinity to 5-HT(4) receptors and has demonstrated potent pharmacological effects on the mid- and distal gut. Tegaserod has been safely employed in clinical trials where it has demonstrated efficacy in normalizing intestinal function, thereby improving irritable bowel syndrome symptoms.

Topics: Constipation; Humans; Indoles; Irritable Bowel Syndrome; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists

The treatment of irritable bowel syndrome with constipation (IBS-C) has historically been based on the severity of symptoms, with education, reassurance, dietary advice, bulking agents and laxative therapy offered as appropriate. Tegaserod (Zelnorm, Zelmac) is the first selective serotonin 5-HT(4) receptor partial agonist to be approved for the treatment of this syndrome. Tegaserod is active against multiple irritable bowel syndrome (IBS) symptoms; it stimulates gut motility and reduces visceral sensitivity and pain. The drug does not cure IBS and was not designed to treat the diarrhoea-predominant version. Its efficacy in men has not been established. Three large well designed clinical trials of tegaserod 6 mg twice daily for 12 weeks in patients (mainly women) with IBS-C have demonstrated superiority versus placebo in global relief from symptoms. Global relief response rates were 38.4-46.8% with tegaserod 6 mg twice daily and 28.3-38.8% with placebo (p < 0.05-0.0001 vs placebo). The relative increases in response rates with tegaserod 6 mg twice daily over the already high responses in the placebo groups ranged from 12-65% after 4-12 weeks of treatment. A response was seen within the first week. The proportion of patients with satisfactory relief from symptoms fell over the 4-week period following withdrawal of tegaserod and placebo, but did not reach baseline levels during this time. Diarrhoea has been associated with tegaserod in clinical trials (an incidence of about 10% versus 5% with placebo, usually occurring in the first week of treatment), but the drug is otherwise well tolerated. There were no apparent changes in the tolerability profile with extended tegaserod treatment (

Topics: Biological Availability; Colonic Diseases, Functional; Constipation; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Indoles; Intestinal Absorption; MEDLINE; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Colonic Diseases, Functional; Constipation; Female; Humans; Indoles; Placebos; Randomized Controlled Trials as Topic; Safety; Serotonin Receptor Agonists; Treatment Outcome

Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind.

Topics: Antidepressive Agents; Benzofurans; Carbolines; Cisapride; Constipation; Drug Industry; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Agonists; Serotonin Antagonists; Serotonin Receptor Agonists

Tegaserod is a medication that has been shown to be of benefit in women with irritable bowel syndrome (IBS) associated with abdominal pain, bloating, and constipation. Tegaserod is a selective serotonin receptor subtype 4 partial agonist designed to interact with the network of cells and nerves throughout the gastrointestinal tract that use serotonin. Tegaserod has been shown to modulate both gastrointestinal motility and visceral sensitivity. Specifically, it increases the peristaltic reflex and decreases visceral sensitivity. Clinical studies have shown that tegaserod improves symptoms of abdominal pain, bloating, and constipation in women with IBS. This article discusses the role of serotonin in gastrointestinal tract physiology, the structure and pharmacokinetic profile of tegaserod, and clinical applications of this new drug.

Topics: Abdominal Pain; Animals; Colonic Diseases, Functional; Constipation; Female; Gastrointestinal Motility; Humans; Indoles; Serotonin; Serotonin Receptor Agonists

Tegaserod, a potent, partial serotonin 4 receptor (5-HT4) agonist, is an effective agent for the treatment of females with constipation-predominant irritable bowel syndrome. Tegaserod enhances gastric motility, stimulates peristaltic reflux and intestinal secretion, inhibits visceral sensitivity, and/or shortens colonic transit time. This agent may help women who have failed to respond to diet and exercise, laxatives, and other forms of therapy. The optimal dose of tegaserod is 6 mg twice daily and results in decreased number of days per month with pain, bloating, and days without bowel movements. Tegaserod is less effective in males than females in the treatment of constipation-predominant irritable bowel syndrome. Tegaserod is well tolerated. Diarrhea is the most frequent adverse effect. The diarrhea tends to occur most frequently during the first few months of therapy and decreases with continued administration.

Topics: Clinical Trials, Phase III as Topic; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Humans; Indoles; Male; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; United States

The most important component of the treatment of irritable bowel syndrome (IBS) is to establish a therapeutic physician-patient relationship, coupled with patient education. We describe a stepwise approach to management, including judicious use of invasive tests, and setting realistic treatment goals that address the dominant symptoms, their severity, and psychosocial factors.

Topics: Abdominal Pain; Antidepressive Agents; Antidiarrheals; Carbolines; Cholinergic Antagonists; Colonic Diseases, Functional; Constipation; Diagnosis, Differential; Diarrhea; Diet; Follow-Up Studies; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Indoles; Middle Aged; Parasympatholytics; Patient Education as Topic; Physician-Patient Relations; Psychotherapy; Randomized Controlled Trials as Topic; Serotonin Antagonists; Serotonin Receptor Agonists; Time Factors

Topics: Abdominal Pain; Animals; Carbolines; Colonic Diseases, Functional; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Male; Serotonin Antagonists; Serotonin Receptor Agonists; Sex Factors

Existing pharmacotherapeutic options for the treatment of patients with irritable bowel syndrome (IBS) are limited in treating the multiple symptoms associated with the disorder. There is much interest in the use of serotonin agents as new therapeutics. Acting primarily through 5-HT3 and 5-HT4 receptors, serotonin elicits changes in motor function and possibly visceral sensation. Two serotonin agents were developed specifically for IBS: tegaserod, a 5-HT4 receptor partial agonist, and alosetron, a 5-HT3 receptor antagonist (which is no longer available). Phase III clinical trial data show that during a 12-week treatment period with tegaserod, IBS patients with abdominal pain and discomfort, bloating, and constipation experienced significant global relief (i.e., improvement in overall well-being, abdominal pain, and bowel habit) compared with placebo. Improvement in bowel movement frequency and consistency was achieved and pain was relieved by 1 week. During 12 weeks of treatment, alosetron was shown to elicit significant relief of abdominal pain and discomfort compared with placebo or mebeverine in female IBS patients with diarrhea. Alosetron slowed colonic transit and treatment efficacy was apparent after a week of treatment. Another 5-HT4 receptor agonist, prucalopride, which is being developed for chronic constipation, accelerates colonic transit and increases stool frequency. Therefore, this agent may be of benefit in IBS patients with constipation.

Topics: Abdominal Pain; Benzofurans; Clinical Trials as Topic; Colonic Diseases, Functional; Constipation; Gastrointestinal Motility; Humans; Indoles; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; United States

The symptoms of irritable bowel syndrome (IBS) are commonly seen in fibromyalgia (FM) patients. This study aimed to evaluate the effect of 5-hydroxytryptamin-4 receptor partial agonist (tegaserod) on the symptoms of FM among the patients who receive the medicine because of IBS. Forty-one female patients with IBS and constipation, which were subjects to tegaserod treatment, were examined by rheumatologist and 14 were found to suffer from FM. The fibromyalgia impact questionnaire (FIQ) and clinical examination were done before tegaserod treatment and 1 month after. The IBS status, the total FIQ score, the number of tender points and pain in tender points were lowered significantly after the treatment (p < 0.001 for all variables). The results of this pilot study provide the preliminary evidence that FM patients can benefit from treatment by 5-hydroxytryptamin-4 receptor partial agonist. Additional studies are needed to support this conclusion.

Topics: Adult; Aged; Comorbidity; Constipation; Female; Fibromyalgia; Follow-Up Studies; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Pilot Projects; Serotonin Receptor Agonists; Surveys and Questionnaires; Treatment Outcome

Tegaserod relieves overall and multiple individual constipation-predominant irritable bowel syndrome (IBS-C) symptoms. However, mechanisms for the relief of abdominal pain/discomfort are not well understood. The effects of tegaserod on rectal sensitivity to distension were measured by the nociceptive flexion RIII reflex, as evidenced by spinal hyperexcitability (i.e. increase or facilitation of the RIII reflex), in IBS-C patients. A randomized, double-blind, placebo-controlled, parallel study was performed in 30 women with IBS-C. The effects of slow ramp rectal distension on the RIII reflex, recorded from the lower limb, were measured before [first experimental day (D1)] and after 7 days [day 8 (D8)] of placebo (n=15) or 6 mg tegaserod bid (n=15). Pressure-volume and sensation-volume relationships were measured during distension, and patients reported their IBS symptoms daily. On D1, rectal distension facilitated the RIII reflex in both treatment groups. On D8 vs D1 these facilitatory effects were significantly lower (P<0.001, analysis of variance) after tegaserod (mean reduction: -30.3+/-11.9%) than placebo (mean reduction: -10.1+/-12.9%). No significant changes in the volume-sensation relationship or differences in compliance were observed with tegaserod or placebo. In conclusion, tegaserod reduces the facilitatory effects of rectal distension on the RIII reflex in women with IBS-C.

Topics: Adult; Compliance; Constipation; Double-Blind Method; Female; Humans; Indoles; Irritable Bowel Syndrome; Manometry; Middle Aged; Placebos; Rectum; Reflex; Serotonin Receptor Agonists

Though the greatest proportion of irritable bowel syndrome (IBS) patients report a mixed bowel pattern (IBS-Mixed), no available therapies have been rigorously evaluated in this subgroup. This study aimed to evaluate the efficacy and safety of the 5-HT(4) agonist tegaserod in women with IBS-Mixed and IBS with constipation (IBS-C).. This prospective, double-blind, randomized, placebo-controlled, multicenter study was conducted in 100 centers in North America, South America, and Europe. Women with IBS-Mixed or IBS-C received tegaserod 6 mg or placebo twice daily. The primary efficacy variable was the patient's assessment of satisfactory relief over the 4-wk treatment period. The proportion of patients reporting satisfactory relief for >/=3 of 4 treatment weeks (75% rule) and individual IBS symptoms were assessed.. In total, 661 women were randomized (IBS-Mixed 324, IBS-C 337). Baseline symptom assessments identified clear differences between the two cohorts. Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk (OR 1.75, 95% CI 1.35-2.25, P < 0.001) in both IBS-Mixed and IBS-C patients. Using the 75% rule, 52.3% of tegaserod-receiving IBS-M patients and 43.3% of IBS-C patients were responders (vs 36.3, OR 1.88, 95% CI 1.16-3.04, P < 0.010; and 28.9, OR 1.90, 95% CI 1.19-3.05, P < 0.008 for placebo, respectively). The most frequent adverse events leading to study discontinuation in tegaserod-treated patients were diarrhea (1.5%) and abdominal pain (0.9%). Overall 7% of IBS-C patients reported diarrhea compared to 12% of IBS-Mixed (placebo 2.4%, 1.8%, respectively).. Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and IBS-C.

Topics: Adult; Constipation; Double-Blind Method; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Patient Satisfaction; Prospective Studies; Treatment Outcome

Chronic constipation/idiopathic constipation is highly prevalent in western countries and traditional treatments are suboptimal. This multicenter study evaluated the efficacy and safety of tegaserod, a selective 5-HT(4) agonist and promotility agent, in men with chronic constipation.. After screening and baseline phases, men with chronic constipation were randomized to receive either tegaserod 6 mg twice daily or placebo in a double-blind manner for 12 wk. Patients recorded symptoms using a diary. Primary efficacy variable was the response rate for an increase in complete spontaneous bowel movements (CSBMs) during the first 4 wk of double-blind treatment. Other efficacy measures included patient assessment of symptoms and satisfaction with symptom relief. Safety and tolerability were also evaluated.. In total, 322 patients were randomized to tegaserod (N = 158) or placebo (N = 164). Increases of at least one CSBM per wk during the first 4 wk of treatment observed for tegaserod compared with placebo (40.5%vs 29.3%, P= 0.03) were sustained throughout the 12-wk treatment period. Response rate for CSBM was also superior for tegaserod (P= 0.04 vs placebo) over the treatment period. Benefits for tegaserod over placebo were also observed for some secondary efficacy variables, however, statistical significance was not achieved at all weeks. Frequency of adverse events was similar with tegaserod and placebo.. Tegaserod 6 mg twice daily was effective and well tolerated in the treatment of chronic constipation in men. Tegaserod provided rapid relief of constipation within 1 wk and the effects were sustained for up to 12 wk.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Chronic Disease; Constipation; Defecation; Double-Blind Method; Drug Administration Schedule; Humans; Indoles; Male; Middle Aged; Retrospective Studies; Serotonin Receptor Agonists; Treatment Outcome

Tegaserod has been shown to be effective in chronic constipation in Western population. Aim We investigated if tegaserod is equally effective in Chinese population.. Two hundred and fifty patients were randomized to a double-blinded 8-week treatment of tegaserod 6 mg b.d. or placebo. Response during weeks 1-4 was defined as an increase in complete spontaneous bowel motion >/=1/week. Secondary efficacy included response during weeks 1-8, individual symptoms and scores, quality of life and global assessment of bowel habits and constipation.. One hundred and nine patients from the treatment group and 107 from the placebo group completed the 8-week treatment. Responder rates was 47.7% vs. 29% for the treatment and placebo groups (P = 0.005). The sustained complete spontaneous bowel motion rate was 29.4% vs. 15.7% in the two groups (P = 0.016). The response rates were higher than that reported previously in the Caucasian studies. There was improvement in the scores for stool form scale, bothersomeness of constipation, abdominal distension/bloating and satisfaction of bowel habit (P < 0.05). The mental score was higher in the treatment group (46.8 +/- 9 vs. 43.6 +/- 10, P = 0.01).. Tegaserod is effective in relieving chronic constipation in Chinese population. The efficacy observed may be higher than that in Western population.

Topics: Adult; China; Chronic Disease; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Treatment Outcome

To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China.. This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs).. A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase > or = 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of > or = 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%).. Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; China; Chronic Disease; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Placebos; Treatment Outcome

To evaluate the potential role of tegaserod in the management of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) in patients with chronic constipation and to determine the possible efficacy of tegaserod on solid-phase gastric emptying and gastric hypersensitivity.. This was an exploratory open-label trial of tegaserod therapy for dyspepsia and reflux symptoms in patients with chronic constipation. The study cohort consisted of 90 patients randomized to three treatment groups for a study period of 4 weeks (tegaserod 6 mg, twice daily; esomeprazole 40 mg, once daily; tegaserod 6 mg, twice daily plus esomeprazole 40 mg, once daily). Twenty healthy volunteers provided control values. Clinical symptoms were evaluated by one of the investigators using a Gastrointestinal Symptom Rating Scale (GSRS). Solid-phase gastric emptying and colonic transit were measured by the radiopaque barium marker method, and the water load test (WLT) was used to evaluate gastric sensation and the function of proximal stomach. The proportions of patients with complete relief of epigastric pain /discomfort, epigastric fullness, early satiety and heartburn in the tegaserod group and the tegaserod plus esomeprazole group were compared with the esomeprazole group, respectively.. The mean global gastrointestinal (GI) scores of all three treatment groups reported using the GSRS showed the same trend, with decreasing scores over the 4-week study period indicating a reported decreasing severity of symptoms that was significantly different from baseline values. Patients in the tegaserod plus esomeprazole group reported the lowest global GI scores after 4 weeks, as expected. Solid-phase gastric emptying (GER) and colonic transit (CTT) increased significantly in the tegaserod 6 mg twice daily group compared with baseline. These parameters did not change in the esomeprazole group at week 4 compared with baseline. In terms of gastric sensation, in the tegaserod group, the proportions of patients with hypersensitivity of the first perception threshold did not change at week 2 or week 4 compared with baseline; however, in this group and in the tegaserod plus esomeprazole group, the proportions of patients with hypersensitivity of discomfort threshold decreased significantly at week 4 compared with baseline. In the esomeprazole group, there were no changes in the proportions of patients with hypersensitivity of the first perception threshold and discomfort threshold at week 2 or 4 compared with baseline. No severe adverse events were recorded, and the medications were in general well-tolerated.. Tegaserod is effective and safe at improving dyspepsia and reflux symptoms in patients with chronic constipation, and tegaserod plus esomeprazole is superior to esomeprazole alone in the resolution of epigastric pain/discomfort and heartburn.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Ulcer Agents; Chronic Disease; Cohort Studies; Constipation; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Transit; Heartburn; Humans; Indoles; Male; Middle Aged; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

In irritable bowel syndrome (IBS), the modulation of neural pathways may be altered and we have recently shown that postprandial recto-sigmoid tone modification is impaired. On pathophysiological grounds, we do not know whether this alteration may have a role in symptom onset and, in particular, whether an effective drug, such as tegaserod, can improve this response together with symptom severity.. Twenty-two female patients with constipation-predominant IBS (IBS-C), diagnosed according to Rome II criteria, were studied. All subjects underwent an evaluation of the presence and severity of IBS symptoms and the recto-sigmoid barostat test to measure fasting and postprandial recto-sigmoid tone and phasic contractility. They were then randomly assigned to receive either tegaserod 6 mg b.i.d (12 patients) or placebo tablets (10 patients) for 4 wk, according to a double-blind protocol. Symptom assessment and recto-sigmoid tone and contractility were re-evaluated at the end of the treatment.. Both symptom severity and postprandial modification of recto-sigmoid tone improved only in the tegaserod group and a significant correlation was evident between the improvement of bloating and the improvement of postprandial recto-sigmoid tone modification. No effect of tegaserod on recto-sigmoid motility index or correlation between motility index and symptom improvement was evident.. In IBS-C female patients, the administration of tegaserod improves symptom severity and is accompanied by an improvement of recto-sigmoid tone response to a meal.

Topics: Adult; Colon, Sigmoid; Constipation; Female; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Muscle Tonus; Rectum; Serotonin Receptor Agonists

The 5-HT(4) receptor agonist tegaserod (6 mg b.i.d.) provides significantly better overall multiple symptom relief compared with placebo in patients with irritable bowel syndrome with constipation (IBS-C). The clinical benefit and safety of tegaserod in IBS-C patients has been demonstrated worldwide in several studies. The aim of this study was to obtain further safety and tolerability data in patients with IBS in the Asia-Pacific region, and to assess patients' satisfaction and compliance with treatment and willingness to re-use tegaserod in a post-marketing setting.. A multicenter, single-arm, open-label trial was conducted at 869 outpatient centers in 10 countries. Men and women with IBS, whose predominant bowel symptom was not diarrhea (non-D-IBS), received tegaserod for 4-12 weeks. Safety and tolerability were assessed by recording adverse events (AE). Patients were questioned about compliance, satisfaction with treatment and willingness to use tegaserod in future.. Data were available from 14 537 patients (18% men, 82% women). Four percent of patients reported at least one AE. The most common AE were diarrhea (2%) and abdominal pain (1%), and most treatment-related AE occurred in the first week of treatment. Serious AE (SAE) were observed in eight patients, and no deaths were reported. Most patients (79%) reported to be satisfied or very satisfied with treatment, and 76% stated they would use tegaserod in the future. Compliance was 97%.. Tegaserod has a favorable safety and tolerability profile for treating non-D-IBS and IBS-C in men and women in the Asia-Pacific region. Satisfaction with tegaserod treatment can be expected in the majority of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asia, Eastern; Child; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Patient Satisfaction; Serotonin Receptor Agonists

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.

Topics: Adult; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Motility; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Radionuclide Imaging; Serotonin 5-HT4 Receptor Agonists; Serotonin Receptor Agonists

Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. This study was designed to compare the efficacy of each product over a 4-wk treatment period.. Study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information.. A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P= 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P= 0.019) and had significantly greater improvement in constipation symptoms (P= 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events.. While PEG laxative and tegaserod are safe for their intended use in chronic constipation, PEG had superior efficacy, caused fewer headaches, and produced greater improvement of constipation symptoms.

Topics: Adult; Aged; Aged, 80 and over; Cathartics; Chronic Disease; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Polyethylene Glycols; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

Tegaserod is approved for the treatment of constipation-predominant irritable bowel syndrome (C-IBS) in females. The aim of this study was to evaluate the effect of tegaserod on colonic transit time (CTT) and symptoms in male patients with C-IBS.. Forty-four males with C-IBS (Rome II) were enrolled. After a baseline washout period of 2 weeks, 40 patients were randomized to 6 mg twice daily of tegaserod or placebo for 12 weeks. Daily bowel habits and weekly satisfactory relief of symptoms were recorded. Total and segmental CTT were measured using radiopaque markers at baseline and after treatment.. The mean +/- SD for the total colonic, right colonic, left colonic and rectosigmoid transit time (in hours) were 18.96 +/- 3.92, 7.74 +/- 1.55, 5.64 +/- 1.51 and 5.58 +/- 2.2 in the tegaserod group compared to 22.47 +/- 3.73, 9.69 +/- 2.33, 6.6 +/- 1.32 and 6.18 +/- 2.22 in the placebo group at the end of 12 weeks. There was a statistically significant difference in the total, right and left CTT in the tegaserod group (P < 0.05) at the end of treatment. Global satisfactory relief at the end of 12 weeks was 75% in the tegaserod group and 50% in the placebo group (P > 0.05). Greater stool frequency occurred in the tegaserod group (P > 0.05). There was a significant decrease in the stool consistency at the end of 12 weeks in patients treated with tegaserod (P < 0.05).. Tegaserod causes significant acceleration of CTT in male patients with C-IBS. Although there was a trend towards improvement in bowel symptoms in the treated group, this effect was not statistically significant.

Topics: Adult; Constipation; Double-Blind Method; Gastrointestinal Agents; Gastrointestinal Transit; Humans; Indoles; Irritable Bowel Syndrome; Male; Serotonin Receptor Agonists

We performed a double-blind randomized placebo-controlled pilot study to determine the efficacy of tegaserod (Zelnorm) in treating constipation in 15 patients with Parkinson's disease (PD). There was a trend for improvement in the Subject's Global Assessment (SGA) of satisfaction with bowel habits (NS) and the total SGA (including abdominal discomfort, bothersome constipation, and satisfaction; NS).

Topics: Aged; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Indoles; Male; Middle Aged; Parkinson Disease; Patient Satisfaction; Serotonin 5-HT4 Receptor Agonists; Serotonin Receptor Agonists

To determine the effect of a laxative alone and in combination with tegaserod in alleviating pain and improving stool frequency in adolescents with constipation predominant irritable bowel syndrome.. Forty-eight postpubertal adolescents of both sexes with constipation predominant irritable bowel syndrome, as defined by Rome II criteria, were randomly allocated to Group A (n = 27) for treatment with a laxative (polyethylene glycol 3350 oral solution) only or Group B (n = 21) for combination therapy with the laxative and tegaserod. Symptoms of abdominal pain (scale 0-10) and frequency of bowel movements were recorded daily in the pre-treatment phase and the post-treatment phase after a 7-day 'washout' period. Patients served as their own controls.. Treatment with the laxative alone (Group A) resulted in significant increase in frequency of bowel movements (P < 0.05), but not significant improvement in pain (P > 0.05). Treatment with the combination of the laxative and tegaserod (Group B) led to significant increase in the frequency of bowel movements and also significant reduction in pain (P < 0.05).. The laxative alone improved stooling but not pain in adolescents with constipation predominant irritable bowel syndrome. Addition of tegaserod resulted in alleviation of pain as well.

Topics: Abdominal Pain; Adolescent; Cathartics; Constipation; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Pain Measurement; Patient Satisfaction; Prospective Studies

To assess the long-term safety and tolerability of tegaserod in patients with chronic constipation (CC).. This 13-month, uncontrolled extension study enrolled CC patients who completed a 12-wk randomized, double-blind, placebo-controlled core study. Patients receiving tegaserod 6 or 2 mg b.i.d. during the core study continued on the same dose; those receiving placebo were switched to tegaserod 6 mg b.i.d (placebo-to-tegaserod). Safety and tolerability were assessed by monitoring adverse events (AEs), laboratory parameters, vital signs, and electrocardiograms. Symptom evaluations included patient satisfaction with bowel habit and bothersomeness of constipation, abdominal distension/bloating, and abdominal discomfort/pain.. A total of 842 patients entered the extension study; 451 (54%) completed. AEs typically occurred within the first month of tegaserod treatment. Long-term treatment neither increased AE incidence nor revealed new safety risks. Headache (11.3%, 14.5%, and 16.1% in the tegaserod 6 mg b.i.d., 2 mg b.i.d., and placebo-to-tegaserod groups, respectively) and abdominal pain (8.8%, 8.8%, 10.9%) were the most common AEs. Diarrhea, the most common drug-related AE (4.9%, 2.5%, 8.0%), rarely led to discontinuation (0.7%, 0.0%, 2.2%). Diarrhea was transient, resolved without treatment interruption or rescue medication, and had no clinically significant consequences. Of 27 serious AEs, none were considered treatment related. No deaths or reports of ischemic colitis occurred in tegaserod-treated patients. No clinically relevant changes occurred in other safety parameters. Safety findings were similar in patients switched from placebo to tegaserod and those maintained on tegaserod.. Tegaserod has a favorable safety profile and is well tolerated during continuous long-term treatment in patients with CC.

Topics: Abdominal Pain; Constipation; Diarrhea; Double-Blind Method; Drug Tolerance; Female; Gastrointestinal Agents; Headache; Humans; Indoles; Male; Middle Aged

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.

Topics: Adolescent; Adult; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Recurrence; Retreatment; Retrospective Studies; Treatment Outcome

Chronic constipation is a common, persistent disorder with limited effective treatment options. This study investigated the efficacy, safety, and tolerability of tegaserod in the treatment of chronic constipation.. After a 2-wk baseline period, patients were randomized to double-blind treatment of 12 wk with tegaserod (2 or 6 mg b.i.d.) or placebo. Response during weeks 1-4 (primary variable) was defined as an increase in complete spontaneous bowel movement (CSBM)/wk. Secondary variables included response during weeks 1-12, patient evaluation of individual symptoms, and global assessment of bowel habits and constipation.. One thousand two hundred and sixty-four patients were randomized to tegaserod or placebo. Responder rates for the primary efficacy variable were 35.6% for tegaserod 2 mg b.i.d. (p= 0.0059 vs placebo), 40.2% for 6 mg b.i.d. (p < 0.0001 vs placebo) and 26.7% for placebo. The number needed to treat was 7.3 for the 6 mg b.i.d. dose compared with 11.1 for tegaserod 2 mg b.i.d. Tegaserod 6 mg b.i.d. reduced straining, abdominal bloating/distension, and abdominal pain/discomfort during the 12-wk treatment period compared with placebo (p < 0.05 for all symptoms). Significant improvements were also seen in stool form and in global assessment of bowel habits and constipation. The most common adverse events, headache and abdominal pain, were more frequent with placebo than with tegaserod.. Tegaserod was efficacious in relieving symptoms of chronic constipation and was well tolerated.

Topics: Chronic Disease; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Serotonin Receptor Agonists

It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use.. To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures.. Women (> or = 18 years of age) with IBS-C according to the Rome II criteria.. Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat.. 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p < 0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p < 0.05).. Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.

Topics: Adolescent; Adult; Aged; Constipation; Double-Blind Method; Drug Administration Schedule; Efficiency; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Serotonin Receptor Agonists; Treatment Outcome

Tegaserod is a promotility agent with proven efficacy and safety in patients with irritable bowel syndrome with constipation.. To assess tegaserod's effect on work productivity and daily activity.. Women, 18-65 years old and meeting Rome II criteria for irritable bowel syndrome with constipation, were randomized to a double-blind, placebo-controlled, multicentre study of tegaserod 6 mg b.d. or placebo. Productivity loss and daily activity impairment because of irritable bowel syndrome were measured with the Work Productivity and Activity Impairment questionnaire for irritable bowel syndrome, modified to exclude diarrhoea as a symptom. Assessments were made at baseline, weeks 2 and 4.. A total of 2660 women were randomized and, of these, 1675 [tegaserod (n = 1363), placebo (n = 312)] were employed and completed Work Productivity and Activity Impairment for irritable bowel syndrome questionnaires. Compared with placebo, tegaserod significantly reduced work and daily activity impairment at weeks 2 and 4. Tegaserod reduced absenteeism by 2.6% (P = 0.004), presenteeism by 5.4% (P < 0.0001), overall work productivity loss by 6.3% (P < 0.0001), and activity impairment by 5.8% (P < 0.0001) at week 4 (vs. baseline). Assuming a 40-h workweek, tegaserod reduced work productivity loss by 2.5 h/week.. Tegaserod significantly reduced work productivity loss and daily activity impairment at 2 weeks, and this benefit was maintained at 4 weeks.

Topics: Absenteeism; Adolescent; Adult; Aged; Constipation; Double-Blind Method; Employment; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Prospective Studies; Serotonin Receptor Agonists; Surveys and Questionnaires; Treatment Outcome; Work

To determine the efficacy and tolerability of tegaserod in the treatment of symptoms of irritable bowel syndrome (IBS) IBS-C patients.. An open label (quasi interventional) study.. Patients were enrolled between October 2000 and August 2001 at 4 centres (AKUH, Karachi; Mayo Hospital, Lahore; PIMS, Islamabad; Hayatabad Teaching Complex, Peshawar).. Tegaserod was administered in a dose of 6 mg (twice-a-day) orally for a period of 6 weeks. Symptoms were assessed before and during treatment using a questionnaire.. The mean age of patients was 37.5 years and 81(69.2%) were males. The study enrolled 117 patients and 101 patients completed the study. Number of bowel movements, symptoms of straining at defecation, stool consistency, bloating, urgency and abdominal pain improved significantly following treatment (p<0.05). Analysis of data in both genders separately showed statistically significant improvement in symptoms of urgency, straining at defecation, abdominal pain and number of bowel movements following treatment. Side effects of diarrhoea and vertigo (6 and 1 patients respectively) necessitating discontinuation of treatment were infrequent.. Tegaserod given in a dose of 6 mg b.d. is effective and well tolerated in IBS-C patients. It is equally effective in males and females in relieving the symptoms of abdominal pain, bloating, straining at defecation as well as increased in the mean number of bowel movements per week.

Topics: Adult; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Treatment Outcome

The post-withdrawal characteristics of tegaserod treatment in patients with irritable bowel syndrome with constipation remain undefined.. To evaluate the effects of continuous tegaserod treatment, versus intermittent or withdrawal of treatment in patients with irritable bowel syndrome with constipation.. In a randomized, open-label trial, all patients initially received tegaserod 6 mg b.d. Responders were randomized to continue or withdraw from treatment for 8 weeks and symptom recurrence was assessed. Tegaserod was re-introduced in withdrawal patients who experienced symptom recurrence, allowing an assessment of intermittent treatment. Two separate analyses assessed the effects of intermittent and withdrawal of treatment on symptom recurrence.. Five hundred irritable bowel syndrome with constipation patients initially received tegaserod; 410 completed treatment. Time to symptom recurrence was shorter in withdrawal patients than those maintained on tegaserod. Significantly more patients maintained on tegaserod had not experienced symptom recurrence by week 8, compared with intermittent (86.5% vs. 58.1%, respectively) or withdrawal of treatment (69.2% vs. 11.3%, respectively) (P < 0.0001 for both). Significant treatment effects were observed for bloating (P < 0.01) and abdominal pain/discomfort (P < 0.02). Most adverse events were mild to moderate.. Irritable bowel syndrome with constipation patients who receive continuous or intermittent tegaserod are less likely to experience symptom recurrence than patients withdrawn from treatment.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Constipation; Female; Flatulence; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Recurrence; Treatment Outcome; Withholding Treatment

Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation.. This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received tegaserod 2 mg twice daily (n = 450), tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of > or =1 complete spontaneous bowel movement/week vs. baseline during weeks 1-4 (primary variable) and weeks 1-12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits.. Responder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group.. Over 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.

Topics: Chronic Disease; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Serotonin Receptor Agonists; Treatment Outcome

To determine the efficacy and safety of tegaserod 6 mg b.i.d. in the treatment of constipation-predominant irritable bowel syndrome (C-IBS).. An 8-week, double-blind, randomized, parallel group, placebo-controlled, multicenter study in 510 Chinese patients who met the Rome II criteria for C-IBS. The study consisted of a 2-week baseline period, a 4-week randomized, double-blind treatment period with either tegaserod 6 mg b.i.d. or placebo (tegaserod:placebo = 1:1), followed by a 2-week withdraw period. Efficacy was assessed by patient's perception of overall symptoms of IBS during the previous week and severity of the patient's constipation during the last week and patient's assessment of their individual IBS symptoms. Safety was assessed by adverse events, laboratory evaluations, blood pressure and heart rates, Physical examination and ECG evaluations.. The weekly severity of patients' perception of overall IBS symptoms was significantly lower in the tegaserod group from week 1 onwards and throughout the treatment period. The effects of tegaserod on secondary IBS efficacy parameters were consistently better in the tegaserod group starting in week 1 and lasting throughout the treatment period and withdraw period. Regarding adverse events during the treatment period, about 10% of the patients in the tegaserod group experienced an adverse event compared to 6% in the placebo group. Diarrhea, abdominal pain and dizziness were more frequent in the tegaserod group but had a low frequency. No serious adverse was observed due to tegaserod.. Tegaserod 6 mg b.i.d. was effective in relieving overall IBS symptoms, constipation, abdominal discomfort and pain, bloating, etc with significant effects starting in week 1 and continuing throughout the treatment period. Tegaserod was generally well-tolerated and has no clinically relevant safety findings.

Topics: Adolescent; Adult; Aged; Constipation; Double-Blind Method; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Treatment Outcome

Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation.. : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits.. A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome.. A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found.. Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Indoles; Male; Middle Aged; Patient Dropouts; Serotonin Receptor Agonists

Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females.. To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation.. In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating.. Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients.. Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

Topics: Adult; Colonic Diseases, Functional; Constipation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Middle Aged; Patient Satisfaction; Prospective Studies; Serotonin Receptor Agonists; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Abdominal Pain; Adult; Colonic Diseases, Functional; Constipation; Dose-Response Relationship, Drug; Female; Humans; Indoles; Male; Middle Aged; Receptors, Serotonin; Receptors, Serotonin, 5-HT4; Serotonin Receptor Agonists; Surveys and Questionnaires; Treatment Outcome

This study evaluated the effects of a partial 5-hydroxytryptamine (5-HT)(4) agonist, tegaserod, on gastric small bowel and colonic transit in constipation-predominant irritable bowel syndrome (IBS).. After a 1 week run-in period, 24 patients with constipation-predominant IBS were randomized to 1 week of tegaserod, 2 mg twice daily, or placebo treatment. Scintigraphic gastric emptying, small bowel transit, and colonic transit were determined before administration of study drug and after 1 week on the medication. Colonic transit was also measured using radiopaque markers and a single radiograph on day 5.. Gastric emptying was unaltered by tegaserod. Proximal colonic filling at 6 hours, a measure of orocecal transit, was accelerated by tegaserod (70.4% +/- 1.3% [mean +/- SEM] vs. placebo, 46.4 +/- 1.9; P = 0.015). Proximal colonic emptying half-time and geometric center at 48 hours were also accelerated by tegaserod compared with baseline, but not compared with placebo. Mean colonic transit time was similar in both groups at baseline and after drug administration (tegaserod, 59.5 +/- 2.1 hours; placebo, 62.1 +/- 2.1 hours).. Tegaserod accelerates orocecal transit, tends to accelerate colonic transit, and deserves further study in patients with constipation-predominant IBS.

Topics: Adult; Aged; Colon; Colonic Diseases, Functional; Constipation; Double-Blind Method; Gastrointestinal Transit; Guanidines; Humans; Indoles; Intestine, Small; Middle Aged; Radionuclide Imaging; Serotonin Receptor Agonists; Stomach; Time Factors

Topics: Abdominal Pain; Constipation; Humans; Indoles; Irritable Bowel Syndrome; Serotonin

Topics: Chronic Disease; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Serotonin Receptor Agonists

Utilization of Theravance's multivalent approach to drug discovery towards 5-HT(4) receptor agonists with a focus on identification of neutral (non-charged at physiological pH) secondary binding groups is described. Optimization of a quinolone-tropane primary binding group with a chiral 2-propanol linker to a range of neutral secondary binding group motifs, for binding affinity and functional potency at the 5-HT(4) receptor, selectivity over the 5-HT(3) receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, afforded velusetrag (TD-5108). Velusetrag has achieved proof-of-concept in patients with chronic idiopathic constipation.

Topics: Animals; Azabicyclo Compounds; Chronic Disease; Constipation; Drug Discovery; Guinea Pigs; Humans; Molecular Structure; Rats; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists; Structure-Activity Relationship

Topics: Cardiovascular Diseases; Constipation; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Platelet Aggregation; Risk Assessment; Serotonin Receptor Agonists

OBJECTIVES. Although Picolax (sodium picosulphate and magnesium citrate) has been widely documented for use in bowel preparation, there is limited literature on its efficacy in the treatment of constipation. Refractory constipation is a more difficult situation with limited treatment options available. The primary objective of this study was to investigate the efficacy of Picolax in the treatment of refractory constipation. DESIGN. Prospective single-centre cohort study. SETTING. The Gastroenterology and Hepatology Centre of a major private hospital in Hong Kong. PATIENTS. Patients aged 18 years or more with chronic constipation refractory to tegaserod or polyethylene glycol and attending the centre in the period of July 2009 to June 2010. RESULTS. A total of 20 patients completed this 6-week single-centre study, with a 2-week baseline assessment and 4-week treatment period. Complete data sets were available for analysis from 17 of these patients. The mean (standard deviation) age of the cohort was 50 (9) years, of which 94% were female. Treatment consisted of half-a-sachet of Picolax taken orally on alternate days, 3 times a week. Patients were required to fill in daily and weekly diary entries of their bowel habit. The mean (standard deviation) number of weekly complete spontaneous bowel movements increased from 0.5 (0.9) to 2.4 (2.6) times per week (P=0.02) after initiation of the treatment, which was a clinically and statistically significant difference; with a mean change of +1.9 (95% confidence interval, 0.3 to 3.4) per week. As a secondary endpoint, 11 patients recorded the use of rescue medication before and after the 4-week treatment. The ratio of patients who took rescue medication decreased significantly from 73% (n=8) to 0% (n=0) [P=0.008]. The mean reduction in the frequency of resorting to rescue medication was 2.6 times (95% confidence interval, -4.2 to -1.1) per week. CONCLUSIONS. Picolax improved the number of complete spontaneous bowel movements and significantly reduced resorting to rescue medication. This formulation could therefore be considered as a treatment option in patients with chronic constipation who are refractory to conventional treatment regimens.

Topics: Adult; Cathartics; Chronic Disease; Citrates; Citric Acid; Cohort Studies; Constipation; Drug Combinations; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Organometallic Compounds; Picolines; Pilot Projects; Polyethylene Glycols; Prospective Studies; Treatment Outcome

Tegaserod, a 5-HT4 agonist, is effective for treating irritable bowel syndrome and chronic constipation. However, sales of this drug were recently suspended due to concerns about a higher rate of cardiovascular events in patients receiving tegaserod over placebo in clinical trials. Our aim was to review patients in our practice prescribed tegaserod to determine if any of them had suffered a cardiovascular event or other significant adverse effects while on this therapy. Additionally, we attempted to determine the efficacy of tegaserod in clinical practice.. Patients with irritable bowel syndrome or chronic constipation in our practice prescribed tegaserod were identified through a search of billing codes and charts reviews. These patients were contacted and questioned about symptoms of cardiovascular events or other adverse events while on tegaserod. The efficacy of this drug was determined by a symptom scale during and after stopping tegaserod.. Sufficient data for analysis was retrieved for 51 of 67 patients prescribed tegaserod. Of these, 37 patients (72.5%) experience no adverse events and 14 patients (27.4%) experienced at least one adverse event, including 6 patients (11.8%) with major adverse events (2 patients (3.9%) with atypical chest pain; 4 patients (7.8%) with syncope; and 2 patients (3.9%) who died. One patient died from advanced pancreatic cancer. The other, who had multiple cardiovascular risk factors as well as a previous myocardial infarction, suffered a cardiac arrest 2 days postoperatively following a below knee amputation, and had actually been off tegaserod for 7 days after hospital admission. Patients graded the severity of both abdominal pain and constipation as worse after stopping therapy compared to during therapy (p<0.0002 and p<0.0001, respectively).. The risk of cardiovascular events during tegaserod therapy may be increased in patients with other risk factors. However, this drug is effective for treating irritable bowel syndrome and chronic constipation, and might be used in a select patient population with severe symptoms but without other risk factors for cardiovascular events.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Chronic Disease; Constipation; Diarrhea; Female; Follow-Up Studies; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Receptors, Serotonin, 5-HT4; Risk Factors; Safety; Treatment Outcome; Young Adult

Topics: Cisapride; Constipation; Gastrointestinal Agents; Humans; Indoles

Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 microg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.

Topics: Animals; Atropine; Clonidine; Constipation; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Gastrointestinal Transit; Indoles; Loperamide; Male; Mice; Mice, Inbred Strains; Mustard Plant; Naloxone; Plant Oils; Transient Receptor Potential Channels; TRPA1 Cation Channel; Yohimbine

Tegaserod is increasingly prescribed by pediatric gastroenterologists even though there are few published data concerning its use in children. The aim of this study was to describe the authors' experience with tegaserod in children.. Patients treated with tegaserod from 2004 through 2006 were included in this study. Defecation and fecal incontinence frequency and global assessment of relief of symptoms were assessed.. Seventy-two patients (44 girls) ranging in age from 1.1 to 18.3 years constitute the patient sample of this report. The median age was 10 years and the median follow-up after initiation of tegaserod treatment was 11.3 months (range 2.3-45.2 months). Indications to prescribe tegaserod were constipation (58%) and a variety of other conditions including functional dyspepsia or inflammatory bowel disease (42%). Defecation frequency increased after tegaserod use (1 vs 7/week, P < 0.001) and presence of fecal incontinence decreased (47% vs 23%, P < 0.001) in the constipation group. Parents rated relief of constipation as moderate or significant in 71% of cases in the constipation group. In the group with other indications to start tegaserod therapy, moderate or significant relief of abdominal pain and bloating was noted in 64% and 68% of patients, respectively. The median dose of tegaserod prescribed was 0.22 mg x kg x day (range 0.05-0.87 mg x kg(-1) x day(-1)). Adverse events were observed in 32% of the patients. The most common side effects were self-limiting diarrhea (20%) and abdominal pain (8%). Only one patient discontinued tegaserod because of side effects; this patient experienced pain at his cecostomy site.. Tegaserod seems to relieve a variety of functional gastrointestinal symptoms in children. Further randomized controlled studies are needed to support the specific pediatric target of prescribing tegaserod.

Topics: Abdominal Pain; Adolescent; Child; Child, Preschool; Constipation; Diarrhea; Dyspepsia; Gastrointestinal Diseases; Humans; Indoles; Infant; Inflammatory Bowel Diseases; Retrospective Studies; Serotonin Receptor Agonists

Topics: Behavior Therapy; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Serotonin Receptor Agonists; Stress, Psychological

The authors conducted a well-designed, multinational, large study of women younger than 65 yr of age with irritable bowel syndrome (IBS) with a mixed pattern of diarrhea and constipation (IBS-M) or constipation (IBS-C) and showed that a statistically greater percentage of patients in each group responded to tegaserod compared with patients treated with placebo. Practicality looms large, however, in that the Food and Drug Administration (FDA) disallowed the continued marketing of tegaserod because of cardiovascular safety concerns, and it now is only available under a restricted access program. The wisdom of this decision aside, it is disturbing that the FDA revealed a zero-tolerance for any significant risk of disease when a drug (e.g., tegaserod) was used for a nonlife-threatening condition; the FDA chose to neglect any potential benefit of significant improvement in quality of life, while at the same time allowing the continued availability of sildenifil for erectile dysfunction and other medications (e.g., rosiglitazone and nonsteroidal anti-inflammatory drugs [NSAIDs]), each with a far greater risk of cardiovascular complications. Whether tegaserod will be re-released and, if so, under what conditions, is yet to be determined, as is the question of whether the FDA will decide to allow a more transparent decision-making process with input from all interested parties affected by their decision.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Constipation; Drug and Narcotic Control; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Paternalism; United States; United States Food and Drug Administration

Topics: Constipation; Drug Interactions; Female; Fluoxetine; Humans; Indoles; Panic Disorder; Serotonin Receptor Agonists

Topics: Cisapride; Constipation; Domperidone; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Indoles; Piperidines; Risk Assessment

To assess the effectiveness of combined drug treatment on megacolon complicated by severe constipation.. Ten patients with megacolon confirmed by barium enema examination, 4 males and 6 females, aged 38 (15 - 66), with a mean course of 10 years (2 weeks - 23 years), all complicated by severe constipation and 5 cases with colonic obstruction confirmed by X-ray examination, 1 being diagnosed as with Hirschsprung' disease, 3 secondary to chronic constipation, 1 with diabetes mellitus, 1 with a history of anorectal malformation, 4 with colonic pseudo-obstruction, and 4 with colonic pseudo-obstruction, were treated with combined conservative therapy including tegaserod (6 mg 2/d), polyethylene glycol (PEG) 4000 (20 - 40 g/d), and liuweianxiao (traditional Chinese medicine, 5 # 3/d). Colon enema was used in the first week if necessary. Follow-up was conducted for 1 - 7 months. The major clinical data included bowel symptoms, complications and adverse effects.. After 1 - 2 weeks of treatment, properties of feces, defecation times, defecation difficulty, and abdominal symptoms, and X-ray findings were all notably improved. No relapse of colonic obstruction was found. The 5 patients with colonic obstruction all showed release. Regarding adverse effect, mild diarrhea was found in 2 cases and was relieved when the dosage was decreased.. Combined drug treatment including tegaserod, PEG 4000 and traditional Chinese medicine is effective in treating megacolon with severe constipation and may help avoid surgical treatment.

Topics: Adolescent; Adult; Aged; Constipation; Drug Therapy, Combination; Female; Humans; Indoles; Male; Medicine, Chinese Traditional; Megacolon; Middle Aged; Polyethylene Glycols; Retrospective Studies; Treatment Outcome

Irritable bowel syndrome (IBS) is a chronic, relapsing disease characterised by abdominal pain and altered bowel movements. This review assesses the clinical trials of the partial serotonin receptor agonist tegaserod in women with constipation type IBS. Significantly more women treated with tegaserod obtained sufficient relief from symptoms during at least 2 out of 4 weeks, but the absolute therapeutic gain of approximately 10 percent was not deemed clinically relevant. Two marketing authorisation applications in the European Union have been rejected due to the minor therapeutic gain. Tegaserod was removed from the market in the USA in March 2007 due to an increased risk of severe cardiovascular adverse events.

Topics: Constipation; Evidence-Based Medicine; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Treatment Outcome

Topics: Asia; Constipation; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Serotonin Receptor Agonists

Topics: Abdominal Pain; Constipation; Diarrhea; Female; Flatulence; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Probiotics

This study was designed to assess the diagnostic and symptom profile of patients receiving tegaserod in routine clinical practice, and to identify their demographic characteristics, as well as the association between these characteristics and diagnosis.. This prospective, observational study collected data from physicians on the symptoms and/or diagnosis, age range and gender for patients to whom they prescribed tegaserod. Details of the physician characteristics included whether they were a family physician or a specialist, and the region of Canada in which their practice was located.. A total of 500 patients were enrolled at 85 sites in Canada. The majority (85%) of the patients were enrolled by family physicians, and the remainder by community-based specialists. The patients were predominantly female (87%) and the highest percentages were in the 35-44 (23%) and 45-54 (25%) age groups. Nearly all patients (96%) were prescribed tegaserod on the basis of both symptoms and diagnosis. The most frequently reported symptoms were abdominal pain and/or discomfort (87%), bloating (80%) and constipation (75%). Most patients (57%) presented with all three of these symptoms. Constipation-predominant Irritable Bowel Syndrome (IBS-C) was the most common diagnosis (55%), followed by IBS alternating between constipation and diarrhea (IBS-A) (23%). Based on this, 67% of patients were given tegaserod strictly according to the label, although it was appropriately prescribed to 87%.. In Canada, tegaserod is prescribed to patients with symptoms of abdominal pain and/or discomfort, bloating and constipation. Most of them will also have a diagnosis of either IBS-C or IBS. It is generally being prescribed appropriately.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Ambulatory Care; Canada; Cohort Studies; Community Health Services; Constipation; Female; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Patient Care; Prospective Studies

Topics: Advertising; Antidepressive Agents; Behavior Therapy; Cathartics; Complementary Therapies; Constipation; Dietary Fiber; Drug Industry; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Serotonin Receptor Agonists

Studies show that tegaserod effectively relieves the symptoms of chronic constipation/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients.. Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks' duration. Post hoc analysis was conducted for the most frequent AEs (incidence, >or=3%).. Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P=.0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups.. Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Chronic Disease; Clinical Trials, Phase III as Topic; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Indoles; Male; Maximum Tolerated Dose; Middle Aged; Patient Satisfaction; Randomized Controlled Trials as Topic; Reference Values; Serotonin Receptor Agonists; Severity of Illness Index; Treatment Outcome

We sought to develop a budget impact model that assesses the economic effect of adding tegaserod for the management of irritable bowel syndrome (IBS) with constipation to the formulary of a managed care organization (MCO). The model estimates the per patient economic impact and the per member, per month (PMPM) economic impact of patients 6 months before and 6 months after the initiation of tegaserod. Resource utilization data, taken from medical and pharmacy administrative claims data, were based on a retrospective, longitudinal study of 3365 patients administered tegaserod through a large, geographically diverse MCO. Costs were estimated for 2 patient subgroups, women with IBS and other gastrointestinal (GI) diagnoses. Sensitivity analyses were performed by varying several model input parameters. The base-case model resulted in an incremental PMPM budget impact associated with the use of tegaserod of 0.01 dollars. Total per patient budget impact (for all resources, including tegaserod) for a 6-month period was 274.34 dollars for women with IBS and 301.84 dollars for women with other GI diagnoses. Overall, 25.9% (29.0% for women with IBS group and 21.9% for women with other GI diagnoses group) of the cost of tegaserod was offset by decreases in resource utilization. Key drivers of post-tegaserod reductions in resource costs were hospital stays, outpatient office visits, emergency department visits, endoscopic procedures, and nonendoscopic procedures. Tegaserod therapy can decrease GI-related resource utilization, resulting in a significant cost-offset percentage. When the associated budget impact of adding tegaserod to its formulary is absorbed across an entire MCO population, the PMPM impact of tegaserod is small.

Topics: Adult; Budgets; Constipation; Cost of Illness; Drug Costs; Drug Prescriptions; Female; Formularies as Topic; Gastrointestinal Agents; Health Care Costs; Humans; Indoles; Irritable Bowel Syndrome; Longitudinal Studies; Managed Care Programs; Middle Aged; Models, Statistical; Retrospective Studies; Serotonin Receptor Agonists; United States; Utilization Review

Irritable bowel syndrome (IBS) has been associated with substantial time lost from work (absenteeism) and reduced productivity at work (presenteeism), which are the indirect costs of illness. This article presents a productivity model demonstrating the indirect costs associated with IBS and the reduction in those costs for a cohort of female employees hypothetically treated with tegaserod, a new selective serotonin (5-hydroxytryptamine [5-HT]) type 4 (5-HT4) receptor agonist, which is approved by the US Food and Drug Administration for treating women with IBS-C. The model is based on economic and epidemiologic published literature and clinical trial results. In this model, tegaserod treatment resulted in 1882 dollars in avoided lost productivity per treated female employee. Considering only the benefits of decreased work loss and the costs of medical therapy, the model predicts a benefit/cost ratio of 3.75 in the base case. From an employer's perspective, medical therapy for IBS with tegaserod is cost-effective under a series of assumptions for the treatment of women with IBS with constipation.

Topics: Absenteeism; Adult; Constipation; Cost of Illness; Cost-Benefit Analysis; Efficiency; Employer Health Costs; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Middle Aged; Models, Econometric; Models, Statistical; Occupational Health; Retrospective Studies; Serotonin Receptor Agonists; United States

Tegaserod, a prokinetic 5-HT4 receptor agonist, has demonstrated efficacy and tolerability in irritable bowel syndrome (IBS) patients with constipation (IBS-C) in controlled clinical trials. Its use in primary care has not been investigated.. To determine whether tegaserod is effective and well tolerated by primary care IBS-C patients.. Patients received tegaserod 6 mg b.i.d. for 12 weeks and were assessed for response, abdominal pain/discomfort, bloating, stool consistency/frequency and straining at weeks 4 and 12. Previous successful treatment with the withdrawn drug, cisapride, was noted. A 9-month study extension was offered to patients completing 12 weeks of tegaserod treatment.. 212 patients entered the 12-week treatment period; 166 completed as planned. Response rates were 64.2% at week 4 and 70.3% at week 12. After 12 weeks, abdominal pain/discomfort and bloating were reduced from baseline (p < 0.0001; mean change -1.02 and -0.91 points, respectively), stool frequency increased (0.78-0.97 stools/day) and stool consistency improved (2.45-3.42; lumpy stools became softer). Tegaserod was well tolerated; the most common adverse events were headache (13.2%) and diarrhea (9.4%). One hundred and twenty patients entered the 9-month extension study, 85 completed and tegaserod continued to be well tolerated.. In ambulatory primary care IBS-C patients, tegaserod is an effective and well-tolerated long-term treatment.

Topics: Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Primary Health Care; Treatment Outcome

Topics: Colitis, Ischemic; Constipation; Humans; Indoles; Irritable Bowel Syndrome

Topics: Chronic Disease; Constipation; Drug Industry; Gastrointestinal Agents; Humans; Indoles; Marketing

Topics: Abdominal Pain; Cathartics; Constipation; Humans; Indoles; Irritable Bowel Syndrome; Patient Satisfaction

Topics: Antineoplastic Agents; Colorectal Neoplasms; Constipation; Female; Gastrointestinal Agents; Humans; Indoles; Inflammatory Bowel Diseases; Male; Needlestick Injuries; Organoplatinum Compounds; Oxaliplatin; Serotonin Receptor Agonists; United States; United States Food and Drug Administration

Topics: Colonic Diseases, Functional; Constipation; Diarrhea; Dose-Response Relationship, Drug; Female; Humans; Indoles; Ovarian Cysts; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists