Tegaserod for Women with IBS
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved the first treatment for women with constipation-predominant irritable bowel syndrome (IBS). Tegaserod is a partial 5-hydroxytryptamine-4 (5-HT4) (serotonin) receptor agonist that increases bowel motility. This approval comes on the heels of the reintroduction of alosetron, a 5-HT3 receptor antagonist, for diarrhea-predominant IBS in women. Tegaserod will be marketed by Novartis under the trade name "Zelnorm."
Tegaserod is indicated for the short-term treatment of women with IBS whose primary bowel symptom is constipation.1
The recommended dosage is 6 mg taken twice daily before meals for 4-6 weeks. For those who respond, an additional course can be considered.1 Dosage adjustment is not required for patients with mild-to-moderate renal impairment or mild hepatic impairment. Food reduces the bioavailability of tegaserod.2
Tegaserod is supplied as 2-mg and 6-mg tablets.
Tegaserod is currently the only FDA-approved drug for the treatment of constipation-predominate IBS. It has a low potential for drug interaction involving the cytochrome P450 isoenzyme system and P glycoprotein. No known significant drug-drug interactions have been identified.1,2 In contrast to other prokinetic-like drugs (eg, cisapride) tegaserod does not cause QT prolongation.
The most common side effect of tegaserod is diarrhea with an incidence of 12% compared to 5% for patients who received placebo. In the majority of the patients diarrhea is limited to 1 episode lasting a median of 2 days, occurring within the first week of therapy. Diarrhea usually resolves with continuous therapy.4 In clinical trials, a higher rate of abdominal surgeries was observed in tegaserod-treated patients compared to placebo (0.3% vs 0.2%). These were mainly cholecystectomies (0.17% vs 0.06%).1
Tegaserod is a selective 5-HT4 receptor partial agonist that stimulates gastrointestinal motility and normalize impaired motility. It increases colonic motility, orocecal transit, and esophageal clearance.3,4 The efficacy of tegaserod was shown in 3 large phase III double-blind, placebo-controlled trials involving about 2500 patients. Tegaserod was shown in these 12-week studies to have a modest effect, compared to placebo, on constipation-predominate IBS. The proportion of responders at the 12 mg/d, ranged from 31-35% the first month and 39-44% the third month compared to 17-22% and 28-39% for placebo, respectively.1 Responders were those who reported considerable or complete relief of symptoms for at least 2 of the 4 weeks of the assessment period. Relief included overall well being, abdominal pain/discomfort, and altered bowel habits. Response rates were statistically significant (P < 0.05) in 2 out of 3 studies.4 Effect was seen as early as the first week and showing the greatest differential from placebo between weeks 4-6.4,5 In addition, compared to placebo, tegaserod improved abdominal pain and discomfort based on a visual analog scale (29.9% vs 22.6%; P = 0.044).5 The drug is well tolerated with less than 2% of patients discontinuing tegaserod due to diarrhea.1,4
Women respond better than men, and currently the drug is only approved for women. The average wholesale cost for a 30-day supply of either strength is about $150.
IBS, as defined by the Rome criteria, is the presence of at least 12 weeks in the preceding 12 months of abdominal discomfort or pain not explained by structural or biochemical abnormalities. The predominate symptoms can be divided into 4 categories, abdominal pain, diarrhea, constipation, or constipation alternating with diarrhea.6 This syndrome is believed to affect 15-20% of the population and affecting 2-3 times more women than men. Current treatment of constipation-predominate IBS includes diet change and laxatives. Tegaserod provides an alternative with modest efficacy.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
1. Zelnorm Product Information. Novartis Pharmaceutical Corporation. July 2002.
2. Baker DE. Rev Gastroenterol Disord. 2001;1(4): 187-198.
3. Lacy BE, Yu S. J Clin Gastroenterol. 2002;34(1):27-33.
4. Camilleri M. Aliment Pharmacol Ther. 2001;15: 277-289.
5. Muller-Lissner SA, et al. Aliment Pharmacol Ther. 2001;15:1655-1666.
6. Horwitz B, et al. N Engl J Med. 2001;344:1846-1850.