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   Vol. V, No. IV
   July/August 2002

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 Update Index


Did You Know....
Irritable Bowel Syndrome:
Two drug options

Irritable bowel syndrome (IBS) is defined as "a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit, with features of disordered defecation and distention." Different classes of medications are utilized in the treatment of IBS, including prokinetic and antispasmodic agents, however, none of these medications are effective in treating all of the symptoms. There are currently many treatment options being investigated for use in IBS, including serotonin-mediated therapy. Serotonin (5-HT) acts as a neurotransmitter, and is widely distributed throughout the gut and central nervous system. Its actions result in smooth-muscle contraction or relaxation, and therefore, can mediate peristalsis, secretory reflexes, nausea, vomiting, bloating, and abdominal pain in the gastrointestinal (GI) tract. The 5-HT3 receptors mediate physiological motor and secretory actions in the GI tract, and can therefore retard small bowel and colonic transit. The 5-HT4 receptors mediate the peristaltic reflex, and can therefore accelerate the small bowel and colonic transit.

Alosetron: Alosetron (Lotronex™; GlaxoSmithKline) is a 5-HT3 receptor antagonist indicated for the treatment of women with diarrhea-predominant IBS. Alosetron inhibits the activation of non-selective cation channels which results in the regulation of visceral pain, colonic transit, and GI secretions. Since constipation is a frequent side effect, alosetron should not be used in patients who are currently constipated or whose predominant bowel movement symptom is constipation. Additionally, alosetron should be discontinued in patients experiencing rectal bleeding and a sudden worsening of abdominal pain. Documented adverse reactions include, but are not limited to: constipation, nausea, and gastrointestinal discomfort, pain, and gaseous symptoms. Due to safety concerns, the recommended initial adult dose of alosetron is 1 mg taken orally once daily for a minimum of 4 weeks. If the initial dosing regimen is ineffective and the patient is not experiencing any adverse reactions, the alosetron dose may be increased to 1 mg taken orally twice daily. There have been no studies in pediatric patients (<18 years of age), nor is there a dosage adjustment required for geriatric patients or patients with renal or hepatic impairment. Although this agent was voluntarily removed from the market in November 2000, due to reports of constipation, ischemic colitis, and death, it has recently been approved by the Food and Drug Administration (FDA) for re-release in the United States. Alosetron, however, is not set to be available until the end of 2002, and physicians will need to be enrolled in a Risk Management Program for prescriptive privileges. The average wholesale price (AWP) of alosetron is approximately $150/month.

Tegaserod maleate: Tegaserod maleate (Zelnorm™;Novartis) was recently FDA-approved on July 24, 2002. It is a 5-HT4 receptor partial agonist indicated for the short term treatment of women with IBS whose primary bowel symptom is constipation. Tegaserod binds with high affinity at human 5-HT4 receptors, thereby stimulating the peristaltic reflex and intestinal secretion, as well as inhibiting visceral sensitivity. Tegaserod is contraindicated in patients with severe renal impairment, and a history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions. Additionally, it should not be initiated in patients who are currently experiencing or frequently experience diarrhea, and should be discontinued in patients with new or sudden worsening of abdominal pain. Adverse reactions of tegaserod include, but are not limited to: abdominal pain, diarrhea, nausea, and headache. The recommended dosage of tegaserod is 6 mg taken orally twice daily before meals for 4 to 6 weeks. If patients are responsive to the initial therapy, an additional 4 to 6 week course may be considered. The tablets are available in 2- and 6-mg strengths. The average wholesale price (AWP) of both the alosetron 2- and 6-mg tablets is approximately $150/month.