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What is Alosetron and explain in detail?
Alosetron, sold under the brand name Lotronex among others, is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. 
It was patented in 1987 and approved for medical use in 2002. It is currently marketed by Prometheus Laboratories Inc. (San Diego). Alosetron was withdrawn from the market in 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, but was reintroduced in 2002 with availability and use restricted.

Medical uses
Alosetron is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS-D) who have: 

chronic IBS symptoms (generally lasting 6 months or longer),
had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and
not responded adequately to conventional therapy.Severe IBS-D includes: diarrhea and 1 or more of the following:

frequent and severe abdominal pain/discomfort,
frequent bowel urgency or fecal incontinence,
disability or restriction of daily activities due to IBS.

Efficacy
The phase III trial for approval was published in 2000 as an industry-funded randomised, placebo-controlled trial (PCT). Its authors found 1 mg alosetron, taken orally twice daily for 12 weeks, was associated with a 12% (CI 4.7-19.2) improvement in relief from abdominal pain and discomfort associated with diarrhoea-predominant patients. The prescription of alosetron is currently approved in the U.S. at 0.5 and 1 mg.The FDA Medical Officers Review, dated November 4, 1999, noted: "Patients considered by investigators to fit the diarrhea-predominant subtype had at baseline... stool consistency values that were neither loose nor watery". The FDAs Gastrointestinal Drugs Advisory Committee referred to the drugs efficacy as "modest", highlighting that the placebo brought relief on the primary outcome measure to 40–50% of women.

Contraindications
Lotronexs prescribing information brochure states that alosetron should not be initiated in patients with constipation. Other contraindications are: history of chronic or severe constipation or sequelae from constipation; intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions, ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; Crohns disease or ulcerative colitis; diverticulitis; severe hepatic impairment. Concomitant use of fluvoxamine is also contraindicated.

Adverse effects
Alosetron was withdrawn in 2000 following the association of alosetron with serious life-threatening gastrointestinal adverse effects. The cumulative incidence of ischaemic colitis was 2 in 1000, while serious complications arising from constipation (obstruction, perforation, impaction, toxic megacolon, secondary colonic ischaemia, death) was 1 in 1000. A 1999 review performed by FDA medical officer John Senior, indicated that 27% of patients experienced constipation. The phase III trial reported constipation occurred in 30% and 3% of patients in the alosetron and placebo groups, respectively. It was cited as the most important reason for patients dropping out of the study.

Mechanism of action
Alosetron has an antagonist action on the 5-HT3 receptors of the enteric nervous system of the gastrointestinal tract. While being a 5-HT3 antagonist like ondansetron, it is not classified or approved as an antiemetic. Since stimulation of 5-HT3 receptors is positively correlated with gastrointestinal motility, alosetrons 5-HT3 antagonism slows the movement of fecal matter through the large intestine, increasing the extent to which water is absorbed, and decreasing the moisture and volume of the remaining waste products.

History
Alosetron was originally approved by the U.S. Food and Drug Administration (FDA) on February 9, 2000, after a seven-month review. At the time of the initial approval U.S. Food and Drug Administration (FDA) reviewers found that alosetron improved symptoms in 10% to 20% of patients.Shipment to pharmacies started in March, 2000