The Food and Drug Administration (FDA) today announced the development of a Medication Guide (FDA-approved patient labeling) to help ensure that women using the prescription drug Lotronex (alosetron hydrochloride) for treatment of the diarrhea-predominant form of irritable bowel syndrome (IBS) will understand the rare but serious risks of Lotronex and how they can recognize those risks and take early action to prevent serious harm. These risks include complications from constipation and the risk of ischemic colitis, a serious complication caused by reduced blood flow to the intestines.
Information for health professionals who prescribe Lotronex has also been updated. Lotronex is a drug with a demonstrated benefit in the treatment of diarrhea- predominant IBS, which can be severely incapacitating. FDA
believes that the benefits of Lotronex outweigh its risks when it is used according to the instructions in the Medication Guide, which reflect the revised professional labeling.
"Today's actions are an important milestone in enabling consumers as well as healthcare professionals to better manage the risks that are inherent in even very beneficial drug treatments, " said FDA Commissioner Jane E. Henney, M.D. "By providing important new safety information about a drug through a Medication Guide to patients, as well as updating the professional labeling, we can better assure that an effective drug can be used safely."
IBS is a functional abnormality of the gastrointestinal tract that is estimated to affect up to 15% of the U.S. population. People with this condition experience chronic or recurrent abdominal pain, and irregular bowel movements including diarrhea, constipation or both. Patients may experience the sudden, urgent need to go to the bathroom or straining when they have a bowel movement. IBS is two to three times more common in women than men.
Lotronex is the first drug to have a Medication Guide under regulations that became effective in 1999. A Medication Guide contains FDA-approved information, written especially for patients, that pharmacists are required to distribute with products FDA has determined pose a serious risk, for which patient labeling can help prevent that risk. In some patients, the risks associated with Lotronex led to hospitalization or surgical procedures not normally associated with IBS.
FDA determined that a Medication Guide is needed for Lotronex because patients play a very critical role in managing the risks of the product. The Medication Guide instructs patients who become constipated while taking Lotronex to call their doctor right away. Patients are instructed to stop taking Lotronex immediately and to contact their doctors if they get severely constipated, have worsening or bothersome constipation with increased abdominal discomfort, or notice signs of ischemic colitis such as new or worsening abdominal (lower stomach area) pain, bloody diarrhea, or blood in their bowel movements. These may be early signs of serious side effects associated with the use of Lotronex.
The Lotronex Medication Guide, which will be attached to every bottle of the drug, also gives patients the following guidance:
- Before starting Lotronex, a woman should discuss with her doctor how troublesome her IBS symptoms are, and the possible benefits and possible side effects of Lotronex, to decide if Lotronex is right for her;
- Lotronex is only for women with IBS who have diarrhea as their main symptom (diarrhea-predominant IBS). Women who have constipation as their main IBS symptom should not use Lotronex;
- Because Lotronex does not cure IBS or work for everyone, women are advised to stop using Lotronex and to tell their doctors if their IBS symptoms do not improve within four weeks of starting the drug; and
- Lotronex has not been shown to help men.
The updated labeling for health professionals states that Lotronex treatment should not be started when women are constipated; and it informs prescribers that Lotronex is now contraindicated in women with:
- a history of intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions;
- a history of ischemic colitis;
- active diverticulitis; or
- current Crohn's Disease or ulcerative colitis, or a history of such a disease.
Between the approval of Lotronex on February 9, 2000, and June 1, 2000, FDA received seven reports of serious complications of constipation. This resulted in the hospitalization of six patients, three of whom required surgery. While 25-30% of patients taking Lotronex in the pre-approval clinical trials had experienced constipation, FDA had received no reports of serious complications before approval.
During the same time period, FDA received eight reports of ischemic colitis in patients taking Lotronex. This resulted in four hospitalizations, four endoscopic procedures and no surgeries. In addition, four cases of ischemic colitis were reported in the clinical studies of Lotronex before approval. All twelve patients with ischemic colitis recovered without serious consequences when Lotronex was discontinued.
Lotronex's sponsor, GlaxoWellcome of Research Triangle Park, N.C., is issuing a "Dear Health Care Professional" letter to inform prescribers of the labeling changes. GlaxoWellcome is also issuing a "Dear Pharmacist" letter to inform pharmacists of their obligation to provide patients a Medication Guide with each Lotronex prescription filled.
Today's announcement follows a detailed review of the adverse event reports and risk management recommendations made by FDA's Gastrointestinal Drugs Advisory Committee at a public meeting on June 27.
The FDA encourages health care providers to report any cases of serious constipation or of ischemic colitis to FDA's MedWatch program by calling 1-800-FDA-1088 or by logging onto FDA's MedWatch site at www.fda.gov/medwatch/.