The FDA is in receipt of at least 49 case reports of ischemic colitis and 5 deaths associated with the use of Lotronexâ (alosetron). A result, the Agency is re-evaluating its decision to approve alosetron for Irritable Bowel Syndrome (IBS). Though the FDA has yet to review the reports, and though a link with Lotronex has not been established, enough concern has been raised to warrant further investigation. Alosetron was originally reviewed in the January 1, 2000 (Volume X, Issue 1) edition of Drug Therapy.

At least one letter was sent to the FDA urging them to withdraw alosetron from the U.S. market (FDA link 1).

The FDA identified the potential for severe constipation and ischemic bowel in its review of the New Drug Application for alosetron. In late June, a scientific advisory committee reviewed the available data and concluded that a stricter warning label was warranted, despite the fact that the rate or cause of ischemic colitis was not fully understood. The FDA now requires that an easy-to-read pamphlet explaining the risk of ischemic colitis, as well as the risk of severe constipation, be distributed to all patients taking the drug. The FDA issued a "Dear Doctor" Letter in August (FDA Link 2)

The FDA's warnings to patients:

• Do not ever take Lotronex if you are constipated most of the time or ever have had severe constipation. If you have severe or worsening constipation while taking Lotronex, stop using it immediately and call your doctor.
• Stop using Lotronex and call your doctor immediately if you have new or worsening pain in the lower abdomen, bloody diarrhea or blood in the stool. These are early symptoms of ischemic colitis.
• Because Lotronex does not cure IBS or work for everyone, quit using it if your symptoms do not improve within four weeks.
• Do not take Lotronex if you have ever had ischemic colitis or other intestinal disorders such as Crohn's disease, ulcerative colitis, or active diverticulitis.

Physicians prescribing alosetron should reinforce the warnings to patients. A patient information sheet is available on line at the PCOI website under Patient Instructions.