Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Review article: the safety profile of tegaserod. 1552 52

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.
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PMID:Tegaserod: a serotonin 5-HT4 receptor agonist for treatment of constipation-predominant irritable bowel syndrome. 1564 12

Treatment of irritable bowel syndrome (IBS) remains challenging for patients and practitioners. Current therapeutic choices include antidepressants and psychotherapy, which are thought to target central nervous system triggers of symptoms. Data supporting these treatments are reviewed. Therapeutic agents targeted at receptors in the enteric nervous system have recently been developed to act locally in the gut. Alosetron, an antagonist for serotonin-3 receptors, reduces intestinal motility, secretion, and possibly sensitivity. It is effective for diarrhea predominant IBS, although there are some potentially serious side effects. Tegaserod, a serotonin-4 receptor agonist, is a prokinetic agent that speeds small bowel transit and right colon transit in IBS, reducing symptoms of constipation, pain, and bloating. IBS symptoms are improved with integration of old and new therapies, combined with reassurance, education, and lifestyle adjustments.
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PMID:Psychotherapeutics and serotonin agonists and antagonists. 1579 92

Based on current evidence, bulking agents are not more effective than placebo at improving global irritable bowel syndrome (IBS)symptoms, although they may increase stool frequency in large doses. Tricyclic antidepressants are more effective than placebo for patients with diarrhea-predominant IBS. Imodium is more effective than placebo at improving stool consistency and decreasing stool frequency in patients with IBS, and it may be an important component for treating diarrhea-predominant IBS. Antispasmodics agents available in the United States are not more effective than placebo for treating IBS, although the studies are small and poorly designed. There are no randomized controlled trials examining the efficacy of laxatives for managing IBS. Tegaserod is more effective than placebo at improving global IBS symptoms in women with nondiarrhea-predominant IBS. Alosetron is more effective than placebo in women with diarrhea-predominant IBS, although its use should be limited to patients who have failed conventional therapy because of its adverse event profile.
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PMID:Efficacy of current drug therapies in irritable bowel syndrome: what works and does not work. 1586 38

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.
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PMID:Budget impact of tegaserod on a managed care organization formulary. 1592 61

This study sought to determine the real-world effectiveness of tegaserod therapy on gastrointestinal (GI)-related resource utilization in a managed care population with a retrospective, longitudinal pre-/post-parallel cohort study of tegaserod users and a matched reference cohort of tegaserod nonusers through medical and pharmacy claims data from a large, geographically diverse, managed care organization. Continuously enrolled benefit-eligible patients newly initiated on tegaserod therapy (index prescription) were identified between August 1, 2002, and June 30, 2003, and were categorized (using International Statistical Classification of Diseases, 9th Revision, Clinical Modification codes) as having irritable bowel syndrome (IBS) or another GI-related disorder (e.g., gastroesophageal reflux disease). GI-related resource utilization (office visits, hospitalizations, emergency department visits, endoscopic and nonendoscopic procedures, and GI drug prescriptions) was determined for the 6-month period before and after the index prescription date for tegaserod users and nonusers. The study population consisted of 3365 tegaserod users and 3364 matched nonusers. Within-cohort differences before and after therapy were tested using the Wilcoxon signed rank test. The mean age of 3365 tegaserod users and 3364 matched nonusers was 47 years (+/-15 years); 92% were women, 47% had an index diagnosis of IBS, and 53% had an index diagnosis of another GI-related disorder. Within-cohort GI resource utilization comparisons before and after therapy initiation showed significant decreases (P < .01) in all utilization categories, except GI drug prescriptions, for tegaserod users; these decreases were not consistently observed for matched nonusers. Tegaserod use appeared to be associated with consistent decreases in GI-related resource utilization after 6 months of therapy; similarly consistent reductions were not observed in tegaserod nonusers. These early findings suggest that tegaserod may provide important clinical and economic benefits.
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PMID:Effectiveness of tegaserod therapy on GI-related resource utilization in a managed care population. 1592 62

Studies have shown that early enteral nutrition in critically ill patients reduces the incidence of morbidity and death. Nonetheless, intolerance to gastric enteral nutrition is common in these patients as a result of gastroparesis. The use of prokinetic agents such as metoclopramide, domperidone, cisapride, and erythromycin can improve gastric emptying, but these agents are not without deleterious adverse effects. Tegaserod, a selective serotonin type 4 receptor partial agonist, was recently approved for treatment of women with irritable bowel syndrome. On the basis of tegaserod's mechanism of action, it was hypothesized that tegaserod may accelerate the return of gastric function in intensive care unit patients with gastroparesis. It would thus provide an additional agent for the management of gastroparesis with a more favorable safety profile. We present 3 case reports of the successful use of tegaserod in intensive care unit patients with impaired gastric motility. To our knowledge, the use of tegaserod in this setting has not been reported or studied previously.
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PMID:The use of tegaserod in critically ill patients with impaired gastric motility. 1596 89

Tegaserod, a potent partial agonist of the serotonin 5-HT4 receptor, is used to treat women with constipation-predominant irritable bowel syndrome. Since the drug's approval, the manufacturer has received infrequent although serious reports of diarrhea and ischemic colitis in patients taking the drug. These instances have led to a recent warning letter to physicians and a change in the prescription labeling of tegaserod. We describe the development of ischemic colitis in a woman who was treated with tegaserod and review the relationship among ischemic colitis, tegaserod use, and irritable bowel syndrome. Potential mechanisms involved in the occurrence of ischemic colitis in patients receiving tegaserod are also discussed.
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PMID:Tegaserod-associated ischemic colitis. 1597 22

Irritable bowel syndrome (IBS) is a debilitating disease, which is characterised by recurrent abdominal cramping and pain, and is associated with either constipation and/or diarrhoea. It is approximately twice as prevalent in women as it is in men and is among the most common gastrointestinal (GI) disorders encountered in primary care. The aetiology of the disease is poorly understood but may include motility dysregulation, visceral sensitivity, inflammation, bacterial infection, dietary antigens, psychological stress, GI surgery or a gut-brain phenomenon. At present, there is no acceptable treatment for IBS, although recent advances indicate that some relief may be achieved by the administration of compounds that act on 5-HT (serotonin) receptors. This suggestion is the result of numerous studies which have shown that 5-HT may exert a number of diverse effects on human GI tissues. In addition, it has emerged that the levels of the 5-HT metabolite (5-HIAA) are raised in the plasma of IBS patients and that administration of 5-HT-like compounds may mimic the symptoms of IBS. It has therefore been proposed that therapy with compounds that act at 5-HT receptors will return the intestine to normal activity and alleviate the pain experienced by these patients. One compound (alosetron, a 5-HT3 receptor antagonist) has already been released onto the market but showed benefit in female patients only and only in those whose primary symptom was diarrhoea. In addition, the compound was recently withdrawn following concerns over its safety. The reasons why alosetron only appears to show efficacy in females, why these treatments are only effective in a subset of the population of IBS patients and why alosetron elicits its particular side effect profile have not been elucidated. One further serotonergic compound, tegaserod (Zelmac, a 5-HT4 receptor agonist), has shown promise for the treatment of patients with constipation-predominant IBS and is currently in pre-registration for this indication. It is clear, however, that further research will have to take place before the utility of serotonergic modulation in the treatment of IBS can be fully validated.
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PMID:Serotonergic modulation and irritable bowel syndrome. 1598 96

Novartis is developing Zelmac (SDZ-HTF-919), a 5-HT4 receptor partial agonist, which is in phase III clinical trials for the treatment of gastric motility disorders and irritable bowel syndrome (IBS). Warburg Dillon Read estimated (in January 1999) that Zelmac will achieve sales of 240 million Swiss Francs in 2001.
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PMID:Zelmac (Novartis AG). 1616 Sep 39


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