tegaserod and Abdominal-Pain

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

Topics: Abdominal Pain; Antidepressive Agents; Biofeedback, Psychology; Clinical Trials as Topic; Combined Modality Therapy; Dyspepsia; Feeding Behavior; Forecasting; Humans; Indoles; Irritable Bowel Syndrome; Meta-Analysis as Topic; Patient Compliance; Probiotics; Psychotherapy; Quality of Life; Relaxation Therapy; Serotonin Receptor Agonists; Stress, Psychological; Surveys and Questionnaires

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 (Zelmac), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5-HT(4) receptor with an affinity constant in the nanomolar range. Tegaserod does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and distributes widely into tissues. Pharmacokinetics of oral tegaserod are linear in the 2--12 mg dose range. After oral administration tegaserod is metabolized mainly pre-systemically; when absorbed, intact tegaserod is excreted as N-glucuronides mainly via the bile. No clinically relevant drug--drug interactions were identified. Tegaserod has proven safe in toxicity studies. In pharmacodynamic studies, tegaserod stimulated the peristaltic reflex in vitro, increased canine intestinal and colonic motility and transit, reduced visceral afferent firing or sensation in response to distension in animals, and accelerated gastric, small bowel and colonic transit in healthy patients, and small bowel transit in patients with constipation-predominant irritable bowel syndrome. Three large phase III randomized, double-blinded, and placebo-controlled trials were performed predominantly in females (approximately 85%) with constipation-predominant irritable bowel syndrome. Overall, phase III results support efficacy as assessed by the subject's global assessment of relief with significant improvement in secondary endpoints such as abdominal pain, bowel frequency and consistency. Tegaserod was well-tolerated; the most frequent adverse event was transient diarrhoea.

Topics: Abdominal Pain; Absorption; Administration, Oral; Animals; Colonic Diseases, Functional; Diarrhea; Dogs; Female; Gastrointestinal Agents; Gastrointestinal Transit; Humans; Indoles; Male; Patient Satisfaction; Randomized Controlled Trials as Topic; Treatment Outcome

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

Topics: Abdominal Pain; Animals; Benzyl Compounds; Carbolines; Central Nervous System; Colitis, Ulcerative; Colon; Colonic Diseases, Functional; Colonoscopy; Controlled Clinical Trials as Topic; Diarrhea; Digestion; Electromyography; Female; Follow-Up Studies; Gastric Emptying; Gastroenteritis; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Indoles; Intestines; Male; Myenteric Plexus; Neurons; Neurotransmitter Agents; Placebos; Pressure; Propylamines; Receptors, Opioid, kappa; Rectum; Risk Factors; Serotonin Antagonists; Serotonin Receptor Agonists; Sex Factors; Time Factors

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

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

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

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

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

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: 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: Abdominal Pain; Anastomosis, Roux-en-Y; Gastrectomy; Gastrointestinal Agents; Humans; Indoles; Jejunostomy; Male; Middle Aged; Nausea; Syndrome; Vomiting

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

Topics: Abdominal Pain; Animals; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Serotonin Receptor Agonists