Medical Editor: John P. Cunha, DO, FACOEP
Zelnorm (tegaserod maleate) is a serotonin agonist used to treat severe, chronic, irritable bowel syndrome (IBS) in women who have constipation (and not diarrhea) as their main bowel problem. Zelnorm is also used to treat chronic constipation in patients younger than 55 years old. The brand name Zelnorm is no longer available in the U.S., but may be used in limited emergency situations. Common side effects of Zelnorm include headache, dizziness, migraine, back pain, joint pain, stomach or abdominal pain, nausea, vomiting, gas, bloating, diarrhea, leg pain, and fatigue.
The recommended dosage of Zelnorm is 6 mg taken twice daily orally before meals for 4 to 6 weeks. Zelnorm may interact with other drugs. Tell your doctor all medications and supplements you use. Zelnorm is not expected to be harmful to a fetus. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.
Our Zelnorm (tegaserod maleate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Read the entire patient information overview for Zelnorm (Tegaserod Maleate)
The following adverse reactions are discussed in more detail elsewhere in the labeling:
- Cardiovascular Ischemic Events, including MACE [see WARNINGS AND PRECAUTIONS]
- Ischemic Colitis [see WARNINGS AND PRECAUTIONS]
- Volume Depletion Associated with Diarrhea [see WARNINGS AND PRECAUTIONS]
- Suicidal Ideation and Behavior [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Common Adverse Reactions
In three clinical trials 2,343 female patients less than 65 years of age with IBS-C received ZELNORM 6 mg twice daily or placebo. The majority of patients were Caucasian. Table 1 provides the incidence of common adverse reactions reported in >2% of IBS-C patients in the ZELNORM treatment group and at an incidence that was greater than in the placebo group.
Table 1: Most Common Adverse Reactionsa in
Three Placebo-Controlled Trials of ZELNORM in Female IBS-C Patients Less than
65 Years of Age
|Adverse Reactions||ZELNORM 6 mg twice daily
[N = 1,184] %
[N = 1,159] %
|a Reported in >2% of ZELNORM-treated
patients and at an incidence greater than placebo
b Includes abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort, abdominal tenderness, epigastric pain or discomfort
The majority (84%) of the ZELNORM patients reporting diarrhea had a single episode. In most cases, diarrhea occurred within the first week of treatment. Typically, diarrhea resolved with continued therapy. Diarrhea resulted in discontinuation in 1.6% of ZELNORM-treated patients compared to 0% in placebo [see WARNINGS AND PRECAUTIONS].
Less Common Adverse Reactions
The following is a list of less common adverse reactions reported in ≤ 2% of patients in clinical trials of IBS-C on ZELNORM but more frequently than placebo:
Blood and Lymphatic System Disorders: Anemia
Ear and Labyrinth Disorders: Vertigo
Gastrointestinal Disorders: Rectal hemorrhage
General Disorders and Administration Site Conditions: Asthenia
Investigations: Increased blood creatine phosphokinase
Metabolism and Nutrition Disorders: Increased appetite
Musculoskeletal and Connective Tissue Disorders: Arthropathy, tendonitis
Nervous System Disorders: Migraine
Adverse Reactions Of Special Interest
ZELNORM is recommended for use in female patients with IBS-C, and is not recommended for other motility disorders [see INDICATIONS AND DOSAGE].
Major Adverse Cardiovascular Events (MACE)
A retrospective analysis of the pooled clinical trial database data (involving 18,645 patients, both male and female) of 29 placebo-controlled trials of IBS-C and other gastrointestinal motility disorders of at least four weeks duration was conducted. An external adjudication of the reported cardiovascular ischemic (CVI) events identified an imbalance in patients taking ZELNORM (13 events, 0.1%) compared to placebo (1 event, 0.01%). A second external adjudication was conducted with additional patient-level information, and used a comprehensive pre-specified methodology regarding both case selection and assessment. This adjudication confirmed seven CVI events (0.06%) on ZELNORM compared to one event (0.01%) on placebo. An imbalance in MACE events (defined as cardiovascular death, non-fatal MI, non-fatal stroke) was observed in patients taking ZELNORM compared to placebo, as reported in both external adjudications. All events occurred in male and female patients with a history of cardiovascular ischemic disease and/or more than one cardiovascular risk factor.
A summary of the event rates from both adjudications is provided in Table 2. The rate of MACE events for ZELNORM-treated patients ranged from 0.03% to 0.06% in the overall population and 0.01% to 0.03% in the female population less than 65 years of age without a history of cardiovascular ischemic disease compared to zero in the placebo-treated group.
Table 2: Number of MACE Events Confirmed in Two External Adjudications of the Clinical Trial Database
|All Patients (Male and Female)||Females < 65 Years of Age|
|Without a History of Cardiovascular Ischemic Diseasea||Without a History of Cardiovascular Ischemic Diseasea and One or Fewer Cardiovascular Risk Factorsb|
|First External Adjudication||7c (0.06%)||0||3e (0.03%)||0||0||0|
|Second External Adjudication||4d (0.03%)||0||1f (0.01%)||0||0||0|
|aDefined as prior MI, stroke, transient
ischemic attack, angina, etc.
bDefined as active smoking, current hypertension/history of antihypertensive treatment, current hyperlipidemia/history of lipid lowering medication, history of diabetes mellitus, age ≥55 years, or obesity (BMI >30 kg/m²).
cFive females less than 65 years, one male less than 65 years and one male greater than 65 years of age
dThree females less than 65 years of age and one male greater than 65 years of age
eCardiovascular death, MI and stroke; all three patients had > one cardiovascular risk factor at baseline
fCardiovascular death (one of the three cases confirmed in the 1st external adjudication)
Two ZELNORM-treated patients committed suicide, one in a controlled study of IBS-C and one during open label treatment for another motility disorder. In 27 placebo-controlled trials, assessing tegaserod at a total daily dose of 4 mg to 50 mg (up to four times the recommended daily dose), or placebo for the treatment of IBS-C or other gastrointestinal motility disorders, the frequency of suicidal ideation/behavior with tegaserod treatment (8 events/10,003, or 0.08%) was higher than placebo (1 event/5,425, or 0.02%). Events on ZELNORM included one completed suicide, two suicide attempts, four cases of selfinjurious behavior, and one case of suicidal ideation. There was one suicide attempt on placebo. Of the eight ZELNORM-treated patients who experienced an event, all were less than 65 years of age, seven were female and three had IBS-C. The patient who committed suicide was a female, less than 65 years of age with IBS-C, taking ZELNORM 2 mg twice daily.
Abdominal Surgeries, Including Cholecystectomy
An increase in abdominal surgeries was observed on ZELNORM (9 patients out of 2,965 or 0.3%) versus placebo (3 patients out of 1,740 or 0.2%) in clinical trials of men and women treated with ZELNORM for IBS-C. The increase was primarily due to a numerical imbalance in cholecystectomies reported in patients treated with ZELNORM (5 patients out of 2,965 or 0.17%) versus placebo (1 patient out of 1,740 or 0.06%). A causal relationship between abdominal surgeries and ZELNORM has not been established.
The following adverse reactions have been identified during postapproval use of ZELNORM. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Ischemic colitis, mesenteric ischemia, gangrenous bowel and rectal bleeding [see WARNINGS AND PRECAUTIONS]
- Severe diarrhea resulting in syncope, hypotension, hypovolemia, electrolyte disorders [see WARNINGS AND PRECAUTIONS]
- Sphincter of Oddi spasm, bile duct stone, cholecystitis with elevated transaminases, elevation in ALT, AST and bilirubin, hepatitis [see CONTRAINDICATIONS]
- Hypersensitivity reactions, including anaphylaxis [see CONTRAINDICATIONS]
Read the entire FDA prescribing information for Zelnorm (Tegaserod Maleate)