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A randomized, double blind, placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome (IBS).Six hundred and sixty-two men were randomized to treatment with alosetron 0.5, 1.0, 2.0, 4.0 mg, or placebo twice daily for 12 wk, followed by a 4-wk posttreatment period. Adequate relief of IBS pain and discomfort during week 5-12 of the treatment phase was the primary endpoint; secondary endpoints included bowel urgency, stool frequency, and consistency, incomplete evacuation, bloating, and abdominal pain or discomfort.Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms. The average rate of adequate relief during week 5-12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo (53%vs 40%, p= 0.04), and all doses of alosetron significantly reduced stool consistency scores (p0.001) indicating firmer stools. No significant effects of alosetron were seen with regard to urgency, number of bowel movements, bloating, and incomplete evacuation. Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron, 9% (0.5 mg twice daily), 15% (1.0 mg twice daily), 11% (2.0 mg twice daily), and 21% (4.0 mg twice daily). No serious adverse events of constipation were reported. One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis.Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort, and improved stool consistency in men with diarrhea-predominant IBS.

To assess long-term safety and efficacy of alosetron in women with severe, chronic diarrhea-predominant IBS and in a subset having more frequent urgency (i.e., bowel urgency at least 10 of 14 days during screening).Randomized patients received either alosetron 1 mg (n = 351) or placebo (n = 363) twice daily during a 48-wk, double-blind study. The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort. Secondary endpoints included 48-wk average satisfactory control rates of urgency, stool frequency, stool consistency, and bloating. Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication.Alosetron-treated patients had significantly greater 48-wk average adequate relief (p= 0.01) and urgency control (p0.001) rates, regardless of rescue medication use, compared with placebo. Results in subjects with more frequent urgency were more robust than those in the overall population (p= 0.005). In weeks without rescue medication use, satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo. Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients (p0.05) in 9 of 12 months and significantly greater urgency control (p0.001) in all months. Adequate relief and urgency control were maintained throughout the treatment. Adverse events and serious adverse events were similar between treatment groups, except for constipation. Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported.Long-term use of alosetron is effective and well-tolerated in women with chronic, diarrhea-predominant IBS, including those with more frequent urgency.

The effective management of irritable bowel syndrome (IBS) is enhanced by a therapeutic relationship between healthcare providers and the patient. This survey focused on addressing the symptoms and impact of IBS in women, as well as physician perceptions regarding IBS. A national survey was undertaken to 1) describe the attitudes, knowledge, treatment strategies, and compliance of women with IBS; 2) compare women with IBS to those without IBS on general health and activity limitations; 3) compare women with IBS to physicians regarding their relative perceptions about the disorder; and 4) determine whether physician gender influenced patient satisfaction.

Nurses in a variety of clinical settings are often involved in educating and managing patients with irritable bowel syndrome, though their knowledge and perceptions of irritable bowel syndrome are not well known. A national survey was undertaken as a part of a larger study of patients and healthcare providers to determine nurses' knowledge of irritable bowel syndrome, including diagnosis, etiology, disease impact, management, beliefs, and attitudes regarding irritable bowel syndrome. In addition, the nurses' perceptions of the effect of irritable bowel syndrome on the patient's lifestyle and the severity of symptoms were compared to those of irritable bowel syndrome patients. One hundred practicing registered nurses were randomly selected and then interviewed by telephone using a questionnaire. A random-digit dialing method was used to identify and recruit 1,014 women with irritable bowel syndrome. The majority of registered nurses interviewed (75%) felt that nurses played a moderate-to-major role in counseling patients with irritable bowel syndrome. Only 13%, however, were aware of the diagnostic criteria for irritable bowel syndrome. The majority of nurse subjects felt the current therapies for irritable bowel syndrome had limited effectiveness varying from 6-21% depending on the symptom being treated. Almost half of the nurses felt they had an important role in management of irritable bowel syndrome and that both they and their patients needed more education about irritable bowel syndrome. There was close agreement between the nurses and the patients with regard to the impact of irritable bowel syndrome. With increased public attention on irritable bowel syndrome as a common problem affecting women, there is a need for nurses working in a variety of settings to have increased knowledge regarding the syndrome. In this article, recommendations are made regarding how to increase nurses' knowledge about this common health problem.

Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study.Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation).A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.

Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate.705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements.The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; Por = 0.02). Results were similar for the average adequate relief rate (treatment effectsor =12%, Por = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae.Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.

Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting3 spontaneous bowel movements (SBMs)/week (withor=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent toor=30 mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia.

Background: The histamine H2 receptor antagonist ranitidine is US FDA-approved for the treatment of gastroesophageal reflux disease and healing of erosive esophagitis in children ≥1 month of age. A low-dose strength of ranitidine is now available in a citrus-flavored 25mg effervescent tablet (dissolved in 5mL of water); this formulation was developed to facilitate use in infants and smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL formulation. Objective: To compare taste preferences for ranitidine (Zantac®) syrup and ranitidine effervescent tablets dissolved in water (Zantac® EFFERdose®) in healthy children aged 4–8 years and their adult caregivers. Study Design and Methods: A randomized, single-blind, crossover, taste test trial was conducted in 102 children and 102 parents/legal guardians. All subjects received a single 45mg dose of each formulation. After tasting both preparations children were asked: “Now that you have tasted both medicines, which one of these medicines do you think tastes better?” Adults were asked four questions to assess whether they would administer the medication to the children. Results: Seventy-one percent (72/102) of the children preferred the taste of the ranitidine effervescent tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The majority of adults (71%) responded that they would prefer to administer the effervescent formulation based on taste. Adverse events consistent with product labeling were mild and were reported in four children and three adults: headache (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n = 1). Conclusion: The taste of the ranitidine effervescent formulation dissolved in water is preferred over the ranitidine syrup. Better taste acceptance may facilitate ease of administration and compliance in pediatric patients.

The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS).Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (/=71% of days) with a lack of satisfactory control of bowel urgency.Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetron- and placebo-treated groups, respectively. No cases of ischemic colitis were reported.Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.

Patient satisfaction in Lotronex® (Aloseton HCl) treated nonconstipated irritable bowel syndrome (IBS) females

Background : Patients with irritable bowel syndrome (IBS) often suffer from multiple comorbid conditions, including: depression, anxiety, migraine, functional dyspepsia, fibromyalgia, and gynecologic disorders. These comorbidlties lead to a cycle whereby IBS and comorbid diseases worsen, with a negative impact on patients' productivity and quality of life (QoL). This prospective registry evaluated the effect of comorbid diseases on QoL and productivity of IBS patients. Method: Patients in primary care and GI specialist practices were evaluated by using Computer Assisted Telephone Interviews and chart review. The prevalence of nine key IBS-rsiatad comorbidities was collected: depression, anxiety, other psychiatric conditions, chronic pelvic pain, endometriosis, migraine, functional dyspepsia, fibromyalgia, and chronic fatigue syndrome. Baseline data on patients' QoL measured by the IBSQOL questionnaire, and lost workplace productivity and activity timp were collected. Patients were stratified into three groups (patients with no IBS-related comorbid conditions, patients with one comorbid condition, and patients with greater than one IBS-related comorbid condition). Results : Data were collected from a total of 1,426 IBS patients who reported 1,374 IBS-related comorbid conditions. Fifty percent of the patients (721) presented with one or more IBS-related comorbid conditions, the most prevalent conditions being depression (27%), anxiety (26%), migraine (15%), and functional dyspepsia (13%). Patients with IBS-related comorbidlties presented with an average of 1.90 comorbiditiee. A higher number of comorbidlties was associated with increasingly lower QoL scores in all nine dimensions (emotional, mental health, sleep, energy, physical functioning, eating habits, social role, main activity, and sexual relations). Patients with at least one comorbidity experienced a greater median productivity loss (3.5 vs. 2.1 days) and leisure time loss (11.2 vs. 6.4 days) in a 4-week period than patients without comorbid conditions. Comorbid conditions were equally prevalent in the newly diagnosed and established IBS patients. Conclusions : IBS patients often have multiple comorbid conditions. The presence of comorbid diseases leads to lower QoL status and larger lost productivity in IBS patients. Given their high disease burden, these patients may require special management.

Purpose: Bowel urgency is one of the most bothersome symptoms for subjects with nonconstipated IBS, affecting subjects on over 70% of days. This study screened for subjects with bowel urgency and compared treatment with Lotronex to placebo. Furthermore, the impact on global improvement of IBS symptoms and the relationship between global improvement and satisfactory control of urgency was evaluated.

Impact of Lotronex® (Alosetron HCL) on workplace productivity and activity time in females with non-constipated irritable bowel syndrome (IBS)