A Randomized, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of 0.5 mg and 1 mg Alosetron in Women With Severe Diarrhea-predominant IBS

Krause, Richard A.; Ameen, Vanessa Z.; Gordon, Susan; West, Marquita A.; Heath, Amy; Perschy, T.; Carter, Eric G.

doi:10.1111/j.1572-0241.2007.01282.x

Cited by 96 publications

(109 citation statements)

References 33 publications

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“…For years, tricyclic antidepressants have been used to help target pain and take advantage of the side effect of constipation to help address stool consistency [12] . Alosetron, a 5HT3 antagonist, was approved for women with severe IBS-D because serotonin has been shown to affect motility and pain, but the side effect profile has limited use of the product [13,14] . Rifaximin, an oral antibiotic, has demonstrated some potential for some IBS-D patients [15,16] .…”

Section: Case Presentation #1mentioning

confidence: 99%

Post-Infectious Irritable Bowel Syndrome with Functional Diarrhea Following C. difficile Infections: Case Studies of Responses Using Serum-Derived Bovine Immunoglobulin

Crawford

Panas

2015

Journal of Gastroenterology and Hepatology Research

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a 57-year old Caucasian female, experienced ongoing diarrhea with alternating bouts of constipation after clearance of her recurrent CDI. Upon use of SBI 5g BID, she noticed better management within a few days. Therapy was reduced to SBI 5g QD to avoid possible constipation and she reports regulation of her bowel habits. Discussion: These cases highlight specific symptoms that result from C. difficile-associated PI-IBS, the management that SBI can provide when considered an option for therapy, and the impact disease manifestations can have on quality of life. These cases further suggest the need for additional study of this nutritional agent in post-C. difficile infectious IBS patients. INTRODUCTIONIrritable bowel syndrome (IBS) has been defined by the presence of abdominal pain in association with an alteration of bowel habits [1,2] . Stool consistency is part of diagnosis and determines whether the patient's IBS is with constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). The symptom classification of IBS has been defined as a functional bowel disorder, and more recently as an inflammatory disease [3,4] . While IBS is a common disorder noted in 9-22% of the population [5] , post-infectious IBS (PI-IBS) may occur in up to nearly a third of gastroenteritis patients and these patients exhibit symptoms ABSTRACTIntroduction: Post-infectious irritable bowel syndrome with diarrhea (PI-IBS-D) may occur after any number of enteric infections. Because these patients tend to experience chronic loose and frequent stools, serum-derived bovine immunoglobulin/protein isolate (SBI) was considered for the management of two patients with IBS-D following recurrent Clostridium difficile infections (CDI). Furthermore, C. difficile toxin binding has been described in an animal model which added to the consideration for its use in two challenging cases. SBI is a prescription medical food intended for the management of chronic loose and frequent stools in patients with IBS-D, inflammatory bowel disease (IBD) and HIV-associated enteropathy. Case Presentations: Both patients were treated for relapsing CDI and eventually cleared. Despite negative retesting for C. difficile, a 39-year old Caucasian female patient developed persistent diarrhea in the setting of intolerance to common therapies. The severity of her condition led her to file for disability. Within two weeks of starting SBI 5 g QID, her frequent loose stools were completely managed but returned upon discontinuation. SBI was restarted resulting again in complete management of frequent loose stools. She now continues on SBI 5g QD and has returned back to work. The second patient, CASE REPORT

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Section: Case Presentation #1mentioning

confidence: 99%

Post-Infectious Irritable Bowel Syndrome with Functional Diarrhea Following C. difficile Infections: Case Studies of Responses Using Serum-Derived Bovine Immunoglobulin

Crawford

Panas

2015

Journal of Gastroenterology and Hepatology Research

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“…Following substantial public pressure, it was re-introduced into the U.S. market in 2002 under a restricted prescribing program and further post-marketing studies are currently underway. In a recent placebo-controlled study, Krause and colleagues examined the safety and efficacy of alosetron at varying doses, and found that one of 250 patients developed self-limited ischemic colitis (0.5 mg daily) [47] . In a systematic review of post-marketing surveillance data, Chang and colleagues estimated the rate of ischemic colitis to be 1.1 per 1 000 patients.…”

Section: -Ht3 Antagonistsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

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“…Compared with placebo, alosetron demonstrated effectiveness in decreasing fecal urgency and improving stool consistency and frequency in women with IBS-D (Figures 1 and 2) [Krause et al 2007;Lembo et al 2004Lembo et al , 2001. Alosetron has been shown to significantly improve IBS-related abdominal pain and discomfort in randomized, double-blind clinical trials (Figure 3) [Krause et al 2007;Camilleri et al 2001Camilleri et al , 2000. [Hahn et al 1997].…”

Section: Efficacy Of Alosetronmentioning

confidence: 99%

“…[Ameen et al 2008;Chang et al 2006] and no confirmed serious outcomes have been reported (e.g. surgeries, transfusions, deaths) to result from these events [Ameen et al 2008;Krause et al 2007;Chang et al 2006]. The risk of developing IC and the pathologic mechanism by which alosetron might cause this adverse event remains unclear [Camilleri, 2007].…”

Section: Postmarketing Surveillance After Reintroduction (November 20mentioning

confidence: 99%

Review: Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant irritable bowel syndrome

Lucak

2010

Therap Adv Gastroenterol

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Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder that causes a range of symptoms. Currently, alosetron hydrochloride (Lotronex Õ ), a selective serotonin type 3 receptor antagonist, is the only medication approved for the treatment of severe diarrhea-predominant irritable bowel syndrome (IBS-D) in women who have inadequately responded to conventional therapy. Alosetron has demonstrated efficacy compared with placebo in clinical trials and has been shown to improve overall health-related quality of life (HRQoL). However, rare instances of ischemic colitis and severe complications of constipation have been reported. As a result, in 2000 alosetron was voluntarily withdrawn from the market but was reintroduced in 2002 with a more restricted indication and a requirement that clinicians and patients follow a prescribing program. Although the efficacy and benefit of alosetron has been clearly demonstrated, it has been used sparingly since its reintroduction. This brief review describes the history of alosetron, efficacy of alosetron in the treatment of IBS, the impact of severe IBS on HRQoL, safety considerations, the risk evaluation and mitigation strategy program under which alosetron is now prescribed, and an update on postmarketing surveillance data.

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A Randomized, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of 0.5 mg and 1 mg Alosetron in Women With Severe Diarrhea-predominant IBS

Cited by 96 publications

References 33 publications

Post-Infectious Irritable Bowel Syndrome with Functional Diarrhea Following C. difficile Infections: Case Studies of Responses Using Serum-Derived Bovine Immunoglobulin

Post-Infectious Irritable Bowel Syndrome with Functional Diarrhea Following C. difficile Infections: Case Studies of Responses Using Serum-Derived Bovine Immunoglobulin

Updates on treatment of irritable bowel syndrome

Review: Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant irritable bowel syndrome

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