General Information

Lotronex was approved for treatment of women with Irritable Bowel Syndrome (IBS) whose predominant bowel symptom is diarrhea and who are non-constipated. The drug treats multiple symptoms of the common disorder, including abdominal pain, urgency, stool frequency, and stool consistency. It was generally well tolerated in clinical studies. (See below for a list of possible side effects).

The approval for treatment of women addresses the fact that 70% of IBS sufferers in the U.S. are female. It also reflects clinical studies that specifically indicate benefits for females.

IBS is one of the most common medical disorders in the U.S., affecting approximately 20% of all adults, yet the cause of IBS is still unknown. The syndrome is manifested by a range of chronic gastrointestinal symptoms, such as recurrent abdominal pain and discomfort, and diarrhea and/or constipation.

Although the safety and effectiveness of Lotronex in men has not yet been determined, research in this area is being conducted. Earlier clinical trials indicated that alosetron is influenced by gender, in that alosetron concentrations were 27% lower in males than in females.

Clinical Results

In two placebo-controlled studies, the efficacy of Lotronex at various doses was investigated in females. In each study 71% of the patients had diarrhea-predominant IBS, while the majority of the remaining population had IBS symptoms alternating between diarrhea and constipation. Only 1% and 2% of the women in studies 1 and 2, respectively, had constipation-predominant IBS.

Results of both studies showed that 1 mg of Lotronex administered twice daily was significantly more effective than placebo in relieving a variety of symptoms of IBS in women. The drug at that dose relieved abdominal pain and discomfort, decreased the proportion of days with urgency, decreased stool frequency, and produced firmer stools.

In study 1, women experienced relief within one week of commencing the study drug. In study 2, this relief began within four weeks. In both studies, effects of the drug were maintained over the course of treatment. Furthermore, in both cases, after discontinuation of the treatment, there was no significant difference between women who had taken the drug and women who had taken the placebo.

Side Effects

Acute ischemic colitis was infrequently reported in patients receiving Lotronex.

Constipation was experienced by 28% of patients taking the drug. The constipation was mild to moderate, and primarily required only laxatives, fiber, or brief interruption of therapy in order to treat the symptom. 10% of patients experiencing constipation as a side effect could not continue with twice-daily dosing. Women with constipation-predominant IBS should not take Lotronex.

All other adverse effects were experienced in less than 8% of the population, with most side effects affecting only 1-3%, always only 1-2% more than placebo. Some of these effects include:

• Hypertension
• Allergic rhinitis
• Throat and tonsil discomfort and pain
• Bacterial ear, nose, and throat infections
• Nausea
• Gastrointestinal discomfort and pain
• Abdominal discomfort and pain
• Gastrointestinal gaseous symptoms.
• Viral gastrointestinal infections
• Dyspeptic symptoms
• Abdominal distention
• Hemorrhoids
• Sleep disorders
• Depressive disorders

Mechanism of Action

Alosetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT3 receptor antagonists such as alosetron inhibit activation of non-selective cation channels which results in the modulation of the enteric nervous system…(FDA Label)

Additional Information

Visit Glaxo Wellcome's own IBS information web site, www.IBSCentral.com. This page is a comprehensive reference guide and interactive site especially for IBS sufferers.

Also, visit the Glaxo Wellcome, Inc. web site to learn more about Lotronex and about other products, research, and services provided by the company that developed this drug. www.glaxowellcome.com

To interact with others that suffer from the disorder, visit the IBS Self Help Group web site: www.ibsgroup.org.
This site also has valuable links about medical research and developments related to Irritable Bowel Syndrome.