Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms.
OBJECTIVE
Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod.


METHODS
After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill > or =2 Rome diarrhea criteria > or =25% of the time. Adverse events were recorded.


RESULTS
Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported.


CONCLUSIONS
In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.
Fidelholtz
James
J
Regional Research Department, Hightop Medical Research Center, Cincinnati, Ohio, USA.
Smith
William
W
Rawls
James
J
Shi
Yingqi
Y
Zack
Anna
A
Rüegg
Peter
P
Lefkowitz
Martin
M
D000328:Adult; D000368:Aged; D003109:Colonic Diseases, Functional / Q000188:drug therapy* / Q000503:physiopathology; D003967:Diarrhea / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012449:Safety
D005765:Gastrointestinal Agents; D007211:Indoles; C105050:tegaserod