Tegaserod In Patients Research Articles

Comparative efficacy of prucalopride and tegaserod in patients with predominantly constipated irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) affects 5-20% of all individuals aroun d the world. In Mexico (Veracruz), a prevalence of 16.9% has been documented. Its diagnosis is based on the Rome III criteria, and its treatment has different approaches; within the pharmacological options are the serotonin receptor agonist drugs (5-HT4). The effectiveness of tegaserod has been established in patients with IBS with constipation (IBS-C), considering prucalopride as a drug with therapeutic potential for this condition, since it shows greater affi nity for the 5-HT4 receptor than tegaserod, and accelerates colonic transit. However, more data from randomized controlled trials that prove this are required. Objective: To compare the efficacy of prucalopride versus tegaserod in the treatment of irritable bowel with constipation, by means of the Bristol scale, the global scale of symptoms and associated symptoms. Material and methods: Two groups of patients were established (A and B) in a randomized manner: men and women between 18 and 50 years of age with Rome criteria III for IBS-C; all were given the same diet. In group A, Prucalopride was administered at a dose of 2 mg orally every 24 hours for two weeks. In group B, 6 mg of tegaserod were administered every 12 hours for two weeks. The clinical evolution of each patient was assessed each week during the two weeks of the study period, including the assessments of the adapted and validated Bristol scale, and the global scale of symptoms and associated symptoms. Results: Twenty-two patients were included, 21 (95.5%) female, with a 1:21 ratio; the average age was 37.27 years; 11 (50%) received prucalopride, and the rest, tegaserod. To evaluate the association between the treatment given and the symptoms of «rectal fullness, evacuation effort and evacuation urgency», Fisher’s exact test was used, being not statistically significant (p > 0.05); for «abdominal distension, abdominal movements and Bristol scale», Mann-Whitney U was used, being not statistically signifi cant (p > 0.05); however, for «abdominal pain», with the same test, a statistically signifi cant difference was found (p < 0.05). Of those treated with prucalopride, one (9%) had diarrhea, three (27%) headache, and one (9%) headache and nausea; with tegaserod, two (18%) had diarrhea, two (18%) headache, and one (9%) headache and nausea. Conclusions: Both, prucalopride and tegaserod improve to some degree all the symptoms evaluated for IBS-C, but prucalopride signifi cantly and more promptly improves the symptom of «abdominal pain». It was evidenced that the diarrea event implied change of treatment in both groups.

M1865 Effects of Combined Therapy with Esomeprazol and Tegaserod in Patients with Extra-Esophageal GERD Not Responsive to Esomeprazol

M1865 Effects of Combined Therapy with Esomeprazol and Tegaserod in Patients with Extra-Esophageal GERD Not Responsive to Esomeprazol

Tegaserod in patients with mechanical sensitivity and overlapping symptoms of functional heartburn and functional dyspepsia

ABSTRACTBackground: While functional heartburn (FH) and functional dyspepsia (FD) are recognized clinical entities, symptoms often overlap across both disorders. Despite their frequency, little is known of the underlying pathophysiology of overlapping symptoms. This study evaluated the effect of the 5-HT4 agonist, tegaserod, on visceral sensitivity and symptom improvement in patients with overlapping symptoms of FH and FD.Research design and methods: Patients with overlapping symptoms of FH and FD (ROME II) and mechanical hypersensitivity (Barostat examination) were randomized to tegaserod 6 mg bid or placebo for 2 weeks with treatment crossover after a 2-week washout period. Esophageal and gastric Barostat sensory tests were performed and patients rated their overall symptoms at study end. When carry-over was detected, data were presented for period 1 only. Safety was also assessed.Results: Sixty patients were screened of whom 30 were randomized and 25 completed. Mechanical hypersensitivity was reported by 83% of 47 patients completing esophageal and gastric baseline Barostat examinations. Tegaserod did not significantly alter balloon volume to pain (primary variable); however, pressure to gastric pain increased (p = 0.044 vs. placebo). The severity of heartburn, regurgitation, early fullness, and bloating was significantly lower following tegaserod vs. placebo treatment (p = 0.026, p = 0.021, p = 0.016, and p = 0.030). Overall symptom improvement was reported by 52% tegaserod vs. 32% placebo patients (p = 0.275), and treatment was well tolerated.Conclusions: Results suggest that tegaserod may increase the gastric pain threshold and decrease the severity of individual symptoms in patients with overlapping FH and FD. However, these findings must be considered within the context of the study limitations, including the small number of subjects, potential for and presence of a carry-over effect, along with the impact of Barostat balloon use on the assessment of gastric function.

The effect of tegaserod in patients with distal intestinal obstruction syndrome

The effect of tegaserod in patients with distal intestinal obstruction syndrome

Sensory signalling effects of tegaserod in patients with irritable bowel syndrome with constipation1

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.

Clinical trial: effects of tegaserod on gastric motor and sensory function in patients with functional dyspepsia

BACKGROUND Tegaserod, a serotonin receptor type-4 partial agonist, stimulates gastrointestinal motility and has been shown to increase gastric volumes before and after a meal in healthy volunteers. Its effect on gastric motor and sensory function in patients with functional dyspepsia is unclear. AIM To evaluate the effects of tegaserod on gastric compliance, accommodation and gastric sensory function in patients with functional dyspepsia and healthy volunteers. METHODS Sixteen patients with functional dyspepsia and 12 healthy volunteers were studied on two occasions, each after a 7-day treatment with either placebo or tegaserod 6 mg b.d. using a double-blind, randomized, crossover design. After each treatment period a gastric barostat study was performed fasting and during intraduodenal lipid infusion. RESULTS Tegaserod increased postprandial gastric compliance in functional dyspepsia patients (P = 0.04). Healthy volunteers showed enhanced postprandial gastric compliance after placebo (P = 0.03). Between-treatment analysis of gastric accommodation revealed a significant increase in intrabag volumes after tegaserod in healthy volunteer (P = 0.04); no difference could be seen in functional dyspepsia patients. Tegaserod had no effect on gastric sensation. CONCLUSIONS Tegaserod enhances postprandial gastric compliance in functional dyspepsia patients and gastric accommodation in healthy volunteers. The improvement of proximal gastric motor function suggests a beneficial role of tegaserod in patients with functional dyspepsia.

Tegaserod-Related Possible Drug Interactions

TO THE EDITOR: I read with great interest the article by Muller-Lissner et al. regarding safety, tolerability, and efficacy of tegaserod in patients with chronic constipation (1). A number of studies have addressed safety issues regarding tegaserod in several indications. However, for any drug, another important measure of safety is the frequency of drug interactions, for which the present study, like the previous ones, also gives no information. The data in hand regarding tegaserod-related drug interactions are limited and restricted to animal studies and individual cases. The authors state in the article that, at baseline, current medications were used as exclusion criteria only when related to intestinal motility, which means that some of the participants were already under medications for other reasons.

A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

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.

Safety, Tolerability, and Efficacy of Tegaserod over 13 Months in Patients with Chronic Constipation

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.

Safety and Tolerability of Tegaserod in Patients With Chronic Constipation: Pooled Data From Two Phase III Studies

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.

An Exploratory Open Label Trial of Tegaserod in Non-Erosive GERD Patients with Incomplete Response to PPIʼs

Purpose: Forty to 50% of patients treated with PPI's for non-erosive GERD (NERD) have persistent upper gastrointestinal symptoms. A previous study has shown that tegaserod improves variables of mechanical hypersensitivity and symptoms in patients with functional heartburn, suggesting tegaserod may be useful in symptomatic NERD. Aim: To determine if addition of tegaserod (6mg BID) to a prescribed PPI regimen improves: (1) Global GERD assessments and (2) occurrence, frequency, severity and distress of 10 upper gastrointestinal symptoms. Methods: This 4-week open-label, randomized, two-center, parallel-group pilot study followed a 4-week screening and 2-week baseline period. NERD patients on stable PPI's for at least 30 days with persistent symptoms were eligible. Treatments were: PPI + tegaserod 6 mg bid (Teg) or PPI alone in a 2:1 allocation. Patients completed weekly and end of treatment global symptom assessments. A GERD Symptom Assessment Questionnaire (GSAQ) was completed at screening and after treatment. A Global Composite Index Score (GCIS) was calculated from the GSAQ. Within-treatment changes from baseline were evaluated using paired t-tests. Between treatment comparisons employed analyses of covariance for continuous parameters, van Elteren's test for ordinal parameters, and Cochran-Mantel-Haenszel tests for dichotomous parameters. Results: Forty-one patients were evaluated (Age 21–63 yrs; 20 Males, 21 Females; n = 27 Teg + PPI; n = 14 PPI). Between treatment comparisons of global GERD assessments vs. pre-study were significant for Teg + PPI at week 1 (p = 0.02) and week 3 (p = 0.03). Occurrence of heartburn/acid reflux, regurgitation, abdominal bloating and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Frequency, severity and bothersomeness of regurgitation and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Teg+ PPI improved the GCIS from baseline to the final visit (p = 0.0002). Tegaserod was well tolerated, with no serious adverse events reported. Conclusions: Tegaserod in combination with a PPI significantly improved several global and individual symptom assessments in NERD patients with incomplete relief from PPI's. Data from this trial justifies investigation of the potential utility of tegaserod in patients with NERD.

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Review article: tegaserod for chronic constipation

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.

A double‐blind, placebo‐controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome

Background: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia‐Pacific populations. This study evaluated the efficacy, safety and tolerability of tegaserod versus placebo in patients with IBS. Methods: Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either tegaserod 6 mg b.i.d. (n = 327) or placebo (n = 320) for a 12‐week double‐blind treatment period. The primary efficacy variable (over weeks 1 to 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 the individual IBS symptoms. Results: Overall satisfactory relief was greater in the tegaserod group than in the placebo group. Over weeks 1 to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the tegaserod group than in the placebo group (95% confidence interval for odds ratio (CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio was 1.78, that is, the odds of satisfactory relief were 78% higher in the tegaserod group than in the placebo group (95% CI (1.35, 2.34), P < 0.0001). A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 (except weeks 1 and 4), with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1–4 and weeks 1–12, respectively. Headache was the most commonly reported adverse event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported by 9.2% of patients on tegaserod (1.3% on placebo) and led to discontinuation in 2.8% of tegaserod patients. Conclusion: Tegaserod 6 mg b.i.d. is an effective, safe and well‐tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom.

Safety and tolerability of tegaserod in patients treated for chronic constipation (CC): A 12-week, double-blind, placebo-controlled multicenter study performed in the americas

Safety and tolerability of tegaserod in patients treated for chronic constipation (CC): A 12-week, double-blind, placebo-controlled multicenter study performed in the americas

Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms

OBJECTIVES: Tegaserod is a selective serotonin (5-HT 4) 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. METHODS: 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 ≥2 Rome diarrhea criteria ≥25% of the time. Adverse events were recorded. RESULTS: 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. CONCLUSIONS: 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.

Clinical pharmacokinetics of tegaserod, a serotonin 5-HT(4) receptor partial agonist with promotile activity.

Tegaserod, a selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT(4) receptor partial agonist, is indicated in patients with irritable bowel syndrome (IBS) who identify abdominal pain or discomfort and constipation as their predominant symptoms. Tegaserod at dosages of 1 to 12 mg/day exerts pharmacodynamic actions in the upper and the lower gastrointestinal tract, accelerating small bowel and colonic transit in patients with IBS. Tegaserod is rapidly absorbed following oral administration; peak plasma concentrations (C(max)) are reached after approximately 1 hour. Absolute bioavailability is about 10% under fasted conditions. Food reduces the bioavailability of tegaserod by 40 to 65% and the C(max) by 20 to 40%. Systemic exposure to tegaserod is not significantly altered at neutral gastric pH compared with the fasted state (pH 2). Tegaserod is approximately 98% bound to plasma proteins, primarily to alpha(1)-acid glycoprotein, and has a volume of distribution at steady-state of 368 +/- 223L. Tegaserod is metabolised mainly via two pathways. The first is a presystemic acid-catalysed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide (M 29.0). This metabolite has negligible affinity for 5-HT(4) receptors and is devoid of promotile activity. The second is direct glucuronidation which leads to generation of three isomeric N-glucuronides. The plasma clearance of tegaserod is 77 +/- 15 L/h, with an estimated terminal half-life of 11 +/- 5 hours following intravenous administration. Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in faeces, with the remainder excreted in urine, primarily as M 29.0. The pharmacokinetics of tegaserod are dose-proportional over the range 2 to 12mg given twice daily for 5 days, with no relevant accumulation. The pharmacokinetics of tegaserod in patients with IBS are comparable to those in healthy individuals, and similar between men and women. No dosage adjustment is required in elderly patients or those with mild to moderate hepatic or renal impairment. Tegaserod should not be used in patients with severe hepatic or renal impairment. No clinically relevant drug-drug interactions with tegaserod have been identified. In vivo drug-drug interaction studies with theophylline [a cytochrome P450 (CYP) 1A2 prototype substrate], dextromethorphan (a CYP2D6 prototype substrate), digoxin, warfarin and oral contraceptives have indicated no clinically relevant interactions and no requirement for dosage adjustment.