Original Contribution
The American Journal of Gastroenterology (2006) 101, 1069–1079; doi:10.1111/j.1572-0241.2006.00459.x
Incidence of Ischemic Colitis and Serious Complications of Constipation Among Patients Using Alosetron: Systematic Review of Clinical Trials and Post-Marketing Surveillance Data
Lin Chang MD1, William D Chey MD, FACG2, Lucinda Harris MD, MSc3, Kevin Olden MD4, Christina Surawicz MD5 and Philip Schoenfeld MD, MSEd, MSc (Epi)2,6
- 1Center for Neurovisceral Sciences & Women's Health, Departments of Medicine, UCLA and VA Greater Los Angeles Healthcare Center, Los Angeles, California
- 2Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan
- 3Department of Gastroenterology, Mayo Clinic, Scottsdale, Arizona
- 4Division of Gastroenterology, University of South Alabama School of Medicine, Mobile, Alabama
- 5Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington
- 6Veterans Affairs Center for Excellence in Health Services Research, Ann Arbor, Michigan
Correspondence: Philip Schoenfeld, MD, VA Ann Arbor Healthcare Systems (111D), 2215 Fuller Road, Ann Arbor, MI 48105.
Received 23 December 2004; Accepted 10 May 2005.
Abstract
BACKGROUND:
Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance.
METHODS:
A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation. Experts were blinded about whether patients used alosetron or placebo. Using pre-specified criteria, experts rated the likelihood of an accurate diagnosis and an association between medication use and adverse events. Cases that were not consistent with the reported diagnosis or not possibly associated with medication use were eliminated from calculation of incidence rates of adverse events.
RESULTS:
Pooled data from clinical trials indicate an increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15%vs 0.0%, respectively, p= 0.03), but there was no significant difference in the rate of serious complications of constipation. All (19/19) alosetron-using patients with ischemic colitis had reversible colitis without long-term sequelae. Based on post-marketing surveillance data, the post-adjudication rate of ischemic colitis is 1.1 per 1,000 patient-years of alosetron use and the rate of serious complications of constipation is 0.66 per 1,000 patient-years of alosetron use.
CONCLUSION:
The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity.
