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IBS Treatment: Alosetron (Lotronex)

Alosetron can be classified as an antidiarrheal agent.  It is a serotonin-3 antagonist (5HT3) and is usually considered for resistant cases of IBS in women.  Other 5HT3 receptor antagonists that are commercially available in the United States include ondonsetron (Zofran) and granisetron (Kytril).  Alosetron is the strongest antagonist and is the only one in this class approved by the FDA for treatment of women with severe diarrhea-predominant IBS.  It is prescribed after unsuccessful trials with other treatments.

How the Medications Work
The gastrointestinal system has an extensive set of neuron receptors along the tracts of the gut.  When these receptors are stimulated, the intestines can become hyperactive.  Alosetron and other 5HT3 receptor antagonists (or blockers) in general work by blocking the neuron receptors, consequently slowing motility of the small and large intestines.  They also reduce water secretion.  All these actions together help prevent diarrhea. 

Side Effects
Some studies have found an association between the use of alosetron and the development of ischemic colitis.  There is no definite explanation why this occurs, but the results can be devastating.  In late 2000, the manufacturers of alosetron voluntarily removed it from United States shelves only to be released again later after public outrage for their withdrawal.  With its second release, alosetron was strictly limited in its use.  It is now a third line of treatment that can only be prescribed by a specialist who is registered with the manufacturer’s prescribing program.  Less than 5% of IBS patients will qualify for treatment with alosetron, namely women with severe diarrhea-predominant IBS.  Common adverse effects include constipation, abdominal pain and nausea.  Rare adverse effects include gastrointestinal disorders such as obstruction, diverticulitis, gastritis, and ulcerative colitis.  Vaginal bleeding and hemorrhage also rarely occur.  The specialist will monitor regularly for signs and symptoms of any abnormalities.

Several large studies have demonstrated that alosetron has superior symptom relieving properties when compared to placebo.  It is initially taken as 1 mg by mouth everyday for four weeks and then increased to 1 mg twice a day for a month.  If the person is not responding (that is, symptoms not decreasing) then the medication is stopped.  Prior to starting the treatment regimen with alosetron, the patient must agree to cooperate fully with the manufacturer’s monitoring program.

References:
Clarke JO, Pearson RL. Irritable Bowel Syndrome. First Consult [web page]. Aug 24 2007; www.mdconsult.com. Accessed June 20, 2008.

El-Baba MF. Irritable Bowel Syndrome. eMedicine [web page]. July 31 2007; www.emedicine.com/med/TOPIC1210.HTM. Accessed June 11, 2008.