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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: alosetron (a LOE se tron)
Brand name(s): LOTRONEX
GENERIC: not available FAMILY: Drugs for Irritable Bowel Syndrome
Find the drug label by searching at DailyMed.

Alternative Treatment [top]

See the box below about alternative treatments for IBS.

Safety Warnings For This Drug [top]

FDA Black-Box Warning

Infrequent but serious gastrointestinal adverse events, some fatal, have been reported with the use of alosetron. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization and, rarely, blood transfusion, surgery and death.

  • Alosetron is indicated only for women with severe diarrhea-predominant (IBS) who have not responded adequately to conventional therapy.

  • Alosetron should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients should immediately report constipation or symptoms of ischemic colitis to their prescriber. Alosetron should not be resumed in patients who develop ischemic colitis. Patients who have constipation should contact their prescriber immediately if the constipation does not resolve after alosetron is discontinued. Patients with resolved constipation should resume alosetron only on the advice of their treating prescriber.

Alternative Treatments for Irritable Bowel Syndrome

General measures include reducing intake of caffeine, alcohol and fried foods. Because intolerance to lactose (milk sugar) can mimic some symptoms of IBS, a test to determine if you are lactose intolerant should be done. Sorbitol, the sugar in sugarless gum or candy, should be avoided. Minimization of stress and the use of relaxation techniques have helped many people. For constipation-predominant IBS, increased dietary fiber and/or the use of psyllium or methylcellulose and increased fluid intake may be helpful. For diarrhea-predominant IBS, the cautious use of loperamide (IMODIUM) can be helpful.

Rome II Criteria for Diagnosis of Irritable Bowel Syndrome[1]

In the preceding 12 months, at least 12 weeks (not necessarily consecutive) of abdominal discomfort or pain that has two out of these three features:

  1. Relieved with defecation.
  2. Onset associated with a change in frequency of stool.
  3. Onset associated with a change in form (appearance) of stool.

Symptoms that cumulatively support the diagnosis of irritable bowel syndrome:

  • abnormal stool frequency (for research purposes, “abnormal” may be defined as greater than three bowel movements per day and less than three per week);
  • abnormal stool form (lumpy/hard or loose/watery);
  • abnormal stool passage (straining, urgency or feeling of incomplete evacuation);
  • passage of mucus;
  • bloating or feeling of abdominal distension.

Facts About This Drug [top]

Alosetron (LOTRONEX) was approved by the Food and Drug Administration (FDA) in 2000 for the management of irritable bowel syndrome (IBS) in women with severe diarrhea as their predominant symptom. The drug is not approved for men.

IBS itself is not a life-threatening condition, although it can be debilitating. If the major symptom is diarrhea, the condition is known as diarrhea-predominant IBS; if it is characterized by constipation, it is called constipation-predominant IBS. The diagnosis...

Alosetron (LOTRONEX) was approved by the Food and Drug Administration (FDA) in 2000 for the management of irritable bowel syndrome (IBS) in women with severe diarrhea as their predominant symptom. The drug is not approved for men.

IBS itself is not a life-threatening condition, although it can be debilitating. If the major symptom is diarrhea, the condition is known as diarrhea-predominant IBS; if it is characterized by constipation, it is called constipation-predominant IBS. The diagnosis of IBS should be based on a set of internationally recognized symptoms known as the Rome II Criteria[1] (see box above) and requires exclusion of treatable causes of the patient’s symptoms, such as ulcerative colitis. This is especially important if the following signs of ulcerative colitis are present: onset after age 50, rectal bleeding, fever, weight loss or anemia. There are no abnormal laboratory tests or changes in the cells of the gastrointestinal (GI) tract on biopsy that can objectively establish the diagnosis of IBS. In fact, the diagnosis of IBS can be made only if the reuslts of all tests for other diseases that might explain the patient’s symptoms are negative and the patient continues to have recurrent abdominal discomfort or pain associated with diarrhea, constipation or both.

Alosetron was inexplicably granted a priority or “fast track” review by the FDA. The justification for granting such a review was that the agency considered alosetron “a significant therapeutic advance” over existing therapies. In fact, alosetron was required to be compared only to a placebo, not to the alternative treatments available.

In truth, the drug is not much better than a placebo. In clinical trials, only 12 to 15 percent of patients actually benefited from the drug. Patients on alosetron improved their abdominal pain/discomfort scores by 0.12 to 0.14 points on a 4-point scale[2],[3] — a trivial benefit. Most patients whose symptoms improve while taking the drug are exhibiting the “placebo effect.”

In late 2000 — only nine months after initial approval — alosetron was withdrawn from the U.S. market. The reason for withdrawal was a life-threatening adverse reaction known as ischemic colitis, a decrease in blood flow to the GI tract that can lead to bleeding, inflammation and perforation of the intestines, sometimes leading to surgery. The condition can result in infection of the abdominal cavity that can be fatal.

Four cases of ischemic colitis had been identified in patients participating in clinical trials even before alosetron was approved. This was “gold standard” evidence that the drug caused a life-threatening adverse drug reaction. But the FDA chose to overlook it. In August 2000, Public Citizen petitioned to ban the drug; there had already been 26 cases of ischemic colitis.[3] We argued that the drug should be available only in a research setting. By April 2002, the FDA had received 84 reports of ischemic colitis and 113 of severe constipation in patients using the drug.[4]

Unfortunately, alosetron returned to the market under restricted conditions in June 2002 after patient groups, some funded by the pharmaceutical industry, demanded the drug’s return. Patients are supposed to be female (there is no evidence alosetron is effective in men); have severe, chronic (lasting longer than six months) diarrhea-predominant IBS; and have failed to respond to other therapies. Among the restrictions imposed in 2002, was the requirement that physicians “self-attest” that they are qualified to diagnose and treat IBS. In addition, both physicians and patients were required to sign consent forms, which were probably intended to protect the manufacturer in product-liability lawsuits.

Public Citizen's Health Research Group argued that even such a highly restricted distribution system was likely to prove inadequate because there are no known factors to predict which women are at the greatest risk of developing ischemic colitis.[5] Therefore, there is no way to adequately warn them which symptoms may lead to this serious adverse reaction or to adequately monitor them, which would be more feasible in the research setting.

With the drug back on the market, cases of ischemic colitis and severe constipation resumed. After a little over a year back on the market, with dramatically decreased sales, alosetron had already been associated with eight cases of ischemic colitis and eight serious complications of constipation.[6]

In 2016, the FDA recklessly decided to ease many of the restrictions on alosetron prescribing that had been imposed in 2002.[7] One of the few remaining restrictions is the requirement that patients prescribed the drug receive an FDA-approved Medication Guide when the prescription is filled.

Groups of patients who must avoid alosetron, according to the FDA[8]

Patients with a history of:

  • chronic or severe constipation 
  • complications from constipation
  • intestinal obstruction, perforation or adhesions
  • ischemic colitis or impaired intestinal circulation
  • thrombophlebitis or a tendency to clot
  • Crohn's disease
  • ulcerative colitis
  • diverticulitis
  • severe liver disease

Patients being treated with the antidepressant fluvoxamine (LUVOX). Fluvoxamine can increase the concentration of alosetron that is present in the bloodstream by almost six times and significantly increase the amount of time the drug remains in the body.

 

last reviewed March 31, 2021