tegaserod and Diarrhea

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

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; 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 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

To evaluate the safety/tolerability and efficacy of tegaserod, a 5-HT4 receptor partial agonist, in the treatment of patients with non-diarrhoea irritable bowel syndrome (non-D-IBS) in Switzerland.. This was an 8-week, open-label, prospective, multicentre study. Patients (> or =18 years old) met the Rome II diagnostic criteria for IBS, excluding those with diarrhoea for > or =14 days in the previous 3 months. Details of IBS symptoms experienced in the preceding week were recorded at visit 1 (day 1). Eligible patients received 6 mg tegaserod twice daily for 8 weeks. Adverse events (AEs) and serious AEs were recorded, along with detailed assessment of diarrhoeal episodes. Efficacy assessments included the overall number and percentage of responders after 8 weeks' treatment.. A total of 850 patients (72% women; mean age, 51.4 years) were enrolled, and 843 received at least one dose of tegaserod. AEs were reported in 38% of patients, of which 13% were drug-related. Diarrhoea occurred early during treatment (13% in the first week, 7% thereafter), was mild to moderate in severity, was transient and was resolved with continued treatment. In total, 208 patients left the study early, primarily due to AEs. Diarrhoea accounted for 68 of these discontinuations. Nine serious AEs were reported but these were not related to tegaserod treatment. Sixty-six percent of patients responded to tegaserod on the Subject's Global Assessment of relief after 8 weeks. Benefits were also seen across individual IBS symptoms.. Tegaserod (6 mg twice daily) appears to be safe, well-tolerated and effective in the treatment of non-D-IBS over 8 weeks.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diarrhea; Female; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Sample Size; Serotonin Receptor Agonists

Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population.. To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region.. A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS.. Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1-4) was the response to the question: "Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS.. The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1-4 (56% v 35%, respectively; p<0.0001) and weeks 1-12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo).. Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.

Topics: Adult; Colonic Diseases, Functional; Diarrhea; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; 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

Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod.. After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill > or =2 Rome diarrhea criteria > or =25% of the time. Adverse events were recorded.. Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported.. In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.

Topics: Adult; Aged; Colonic Diseases, Functional; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Indoles; Intestines; Male; Middle Aged; Safety

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

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

Topics: Diarrhea; Female; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome

Topics: Colitis, Ischemic; Diarrhea; Humans; Indoles; Irritable Bowel Syndrome; Serotonin Receptor Agonists

Topics: Clinical Trials as Topic; Colonic Diseases, Functional; Diarrhea; Female; Gastrointestinal Agents; Humans; Indoles

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