Alosetron (Lotronex)

Trade name Lotronex

Oral agent.

Bioavailability 50–60%.

Protein binding 82%.

Metabolism via hepatic enzymes including CYP2C9, CYP3A4 and CYP1A2.

Biological half-life 1.5–1.7 hours.

Excretion-Renal 73%, fecal 24%

A 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only.

Associated with severe constipation, ischemic colitis and deaths.

It was the first drug returned to the U.S. market after withdrawal for safety concerns.

Indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS-D) who have: chronic IBS symptoms (generally lasting 6 months or longer),

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.

Should not be initiated in patients with constipation.

Other contraindications include 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; Crohn’s disease or ulcerative colitis; diverticulitis; severe hepatic impairment.

The phase III placebo-controlled trial (PCT) found 1 mg alosetron, taken orally twice daily for 12 weeks, was associated with a 12% improvement in relief from abdominal pain and discomfort associated with diarrhea-predominant patients.

Currently approved in the U.S. at 0.5 and 1 mg.

Was withdrawn in 2000 following the association with serious life-threatening gastrointestinal adverse effects.

The cumulative incidence of ischemic colitis was 2 in 1000, while serious complications arising from constipation including obstruction, perforation, impaction, toxic megacolon, secondary colonic ischemia, and death was 1 in 1000.

27%-30% of patients experience constipation.

Works as an antagonist action on the 5-HT3 receptors of the enteric nervous system of the gastrointestinal tract.

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.


Can place on site Alosetron

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