Medications and Drugs

NOTE: On March 30, 2007, the FDA notified healthcare professionals and patients that Novartis had agreed to discontinue marketing tegaserod (Zelnorm) for the short-term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years of age with chronic constipation. FDA analysis of safety data pooled from 29 clinical trials involving over 18,000 patients showed an excess number of serious cardiovascular adverse events, including angina, heart attacks, and stroke, in patients taking tegaserod (Zelnorm)  compared to patients taking placebo.

Medical and Pharmacy Editor: Jay Marks, M.D.

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Pharmacy Author: Emmanuel Saltiel, Pharm.D.
Medical Editor: Jay Marks, M.D.

GENERIC NAME: tegaserod

BRAND NAME: Zelnorm

DRUG CLASS AND MECHANISM: Tegaserod is an oral medication for the treatment of constipation and constipation-predominant irritable bowel syndrome (IBS) in women. IBS is a chronic gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and altered bowel function which may be either constipation or diarrhea. As many as 20% of American adults may suffer from IBS.

Contractions of the intestinal muscles, primarily those of the colon, control the movement of food through the intestine. In constipated patients, there are fewer contractions than in persons without constipation. An important factor that controls the contractions is serotonin. Serotonin is a chemical manufactured by nerves in the intestine. It is released by the nerves and then travels and binds to receptors on the surface of nearby nerves. It is a "neurotransmitter," a chemical messenger, that is, a chemical that nerves use to communicate with each other. When it binds to receptors on the nerves that control contractions of the intestinal muscles, serotonin can either promote or prevent contractions depending on the type of receptor it binds to. Binding to some types of receptors causes contractions, and binding to other types of receptors blocks contractions.

The serotonin 5-HT4 receptor is a receptor that prevents contractions when serotonin binds to it. Tegaserod blocks the 5-HT4 receptor and prevents serotonin from binding to it. As a result, contractions increase. The increased contractions speed the transit of digesting food and reverse the constipation. In addition, tegaserod reduces the sensitivity of the intestinal pain-sensing nerves and can thereby reduce the perception of pain. Tegaserod was approved by the FDA in July, 2002.

PRESCRIPTION: Yes

GENERIC AVAILABLE: No

PREPARATIONS: White, round tablets of 2 and 6 mg.

STORAGE: Tegaserod tablets should be stored at room temperature, 59-86°F (15-30°C).

PRESCRIBED FOR: Tegaserod is used for the short-term treatment of women with IBS whose primary bowel symptom is constipation. It also is approved for the treatment of chronic, idiopathic constipation in men and women less than 65 years of age.

DOSING: The usual dose of tegaserod is 6 mg twice daily, most frequently for 4 to 12 weeks. Tegaserod can be taken with or without food. Older persons do not require lower doses than younger persons.

DRUG INTERACTIONS: There are no known drug interactions with tegaserod. Other drugs that increase intestinal contractions will likely lead to more diarrhea if used together with tegaserod.

PREGNANCY: No ill effects were seen in the fetuses of pregnant rats given 15 times the human dose and rabbits given 50 times the human dose of tegaserod (on a per-weight basis). Nevertheless, there are no adequate studies of tegaserod in pregnant women. Therefore, physicians must weight the potential benefit of giving tegaserod during pregnancy against the unknown risk.

NURSING MOTHERS: Tegaserod is secreted into the breast milk of nursing rats. Very high doses of tegaserod in mice cause tumors. Due to the demonstration of these tumors and the lack of safety data in children, physicians must weigh the potential benefit of giving tegaserod to nursing women against the unknown risk to the infant.

SIDE EFFECTS: Tegaserod is well tolerated in most patients. The most commonly reported side effects are headache (1 in 6 patients), abdominal pain (1 in 8), and diarrhea (1 in 11). Only diarrhea has been reported substantially more frequently than with placebo treatment (sugar pill). Rarely the diarrhea is severe, leading to hospitalization for dehydration and requiring intravenous fluids. Ischemic colitis has been seen rarely in patients taking tegaserod although it is not clear if there is a causal relationship. Patients who develop signs of ischemic colitis--worsening abdominal pain, bloody diarrhea--should stop taking tegaserod and contact their physicians.

Following release of tegaserod, a safety analysis showed an excess number of serious cardiovascular adverse events, including angina, heart attacks, and stroke, in patients taking tegaserod compared to patients taking placebo. Therefore, patients should seek emergency medical care if they experience severe chest pain, shortness of breath, sudden onset of weakness or difficulty walking or talking, or other symptoms of a heart attack or stroke.

Reference: FDA Prescribing Information

Last Editorial Review: 4/21/2008

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