Safety

EXTENSIVE STUDIES HAVE ESTABLISHED THE SAFETY OF ZELNORM IN FEMALE PATIENTS UNDER AGE 65 WITH IBS-C1


Female patients less than 65 years of age

In female patients <65 years of age without a history of CV ischemic disease and ≤1 CV risk factor, there were no CV ischemic events in ZELNORM or placebo-treated patients in either evaluation.1

Female patients less than 65 years of age
 

In female patients <65 years of age without a history of CV ischemic disease and ≤1 CV risk factor, there were no CV ischemic events in ZELNORM or placebo-treated patients in either evaluation.1

NUMBER OF MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) CONFIRMED IN 2 EXTERNAL EVALUATIONS OF THE CLINICAL TRIAL DATABASE1

Females <65 Years of Age
All Patients (Male and Female)Without a History of Cardiovascular Ischemic DiseaseaWithout a History of Cardiovascular Ischemic Diseasea and One or Fewer Cardiovascular Risk Factorsb
ZELNORM
(N=11,614)
n (%)
Placebo
(N=7,031)
n (%)
ZELNORM
(N=9,547)
n (%)
Placebo
(5,748)
n (%)
ZELNORM
(N=7,785)
n (%)
Placebo
(N=4,686)
n (%)
First External Adjudication7c
(0.06%)
03e
(0.03%)
000
Second External Adjudication4d
(0.03%)
01f
(0.01%)
000
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 >1 cardiovascular risk factor at baseline.
fCardiovascular death (one of the three cases confirmed in the 1st external adjudication).

MOST COMMON ADVERSE REACTIONSa IN 3 PLACEBO-CONTROLLED TRIALS OF ZELNORM IN FEMALE IBS-C PATIENTS LESS THAN 65 YEARS OF AGE1

Adverse ReactionsZELNORM 6 mg twice daily
[N = 1,184]
%
Placebo
[N = 1,159]
%
Headache1410
Abdominal Painb1110
Nausea87
Diarrhea83
Flatulence65
Dyspepsia43
Dizziness43
aReported in >2% of ZELNORM-treated patients and at an incidence greater than placebo.
bIncludes abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort, abdominal tenderness, epigastric pain, or discomfort.

Of patients who experienced diarrhea during treatment with ZELNORM, 84% had a single episode. A single diarrhea episode typically occurred within the first week of therapy and resolved with continued treatment.1

ZELNORM is contraindicated in patients with1:

  • A history of myocardial infarction, stroke, transient ischemic attack, or angina
  • A history of ischemic colitis or other forms of intestinal ischemia
  • Severe renal impairment (eGFR< 15 mL/min/1.73 m2) or end-stage renal disease
  • Moderate or severe hepatic impairment (Child-Pugh B or C)
  • A history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
  • Hypersensitivity to tegaserod

Indication

ZELNORM (tegaserod) is indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C).

Important Safety Information

ZELNORM should be used in females under 65 years of age who do not have a history of ischemic cardiovascular disease and who have no more than one CVD risk factor. CVD risk factors are defined 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).

Contraindications:

ZELNORM is contraindicated in patients with:

  • History of myocardial infarction (MI), stroke, transient ischemic attack (TIA), or angina
  • History of ischemic colitis or other forms of intestinal ischemia
  • Severe renal impairment (eGFR< 15 mL/min/1.73 m2) or end-stage renal disease
  • Moderate and severe hepatic impairment (Child-Pugh B or C)
  • History of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
  • Hypersensitivity to ZELNORM

Warnings and Precautions

Cardiovascular Ischemic Events, Including Major Adverse Cardiovascular Events (MACE): Stroke, MI, and cardiovascular death have been reported in adults taking ZELNORM who had an increased risk of developing an adverse cardiovascular event based on their medical history.

Female patients less than 65 years of age should be assessed for a history of cardiovascular disease and cardiovascular risk factors prior to treatment with ZELNORM.

Discontinue ZELNORM in patients who experience an MI, stroke, TIA, or angina. Evaluate the risks and benefits of continued use of ZELNORM in patients who develop evidence of cardiovascular ischemic heart disease (e.g., coronary artery disease) and/or experience changes in health status that could increase cardiovascular risk during treatment with ZELNORM.

Ischemic Colitis: Ischemic colitis and other forms of intestinal ischemia have been reported postmarketing in patients receiving ZELNORM. Discontinue ZELNORM in patients who develop symptoms of ischemic colitis, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain.

Volume Depletion Associated with Diarrhea: In postmarketing experience, serious consequences of diarrhea including hypovolemia, hypotension, and syncope have been reported in patients treated with ZELNORM. Avoid use of ZELNORM in patients who are currently experiencing or frequently experience diarrhea. Instruct patients to discontinue ZELNORM and contact their healthcare provider if severe diarrhea, hypotension, or syncope occur.

Suicidal Ideation and Behavior: Monitor all ZELNORM-treated patients for clinical worsening of depression and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment. Counsel family members and caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Instruct patients to immediately discontinue ZELNORM and contact their healthcare provider if their depression is persistently worse or they are experiencing emergent suicidal thoughts or behaviors.

Common Adverse Reactions (incidence >2% and greater than placebo)

The most common adverse reactions in 3 placebo-controlled trials of ZELNORM in female IBS-C patients less than 65 years of age: headache (14% vs 10% placebo), abdominal pain (11% vs 10%), nausea (8% vs 7%), diarrhea (8% vs 3%), flatulence (6% vs 5%), dyspepsia (4% vs 3%), and dizziness (4% vs 3%).

Use in Specific Populations

  • Pregnancy: Safety and effectiveness not established
  • Lactation: Breastfeeding not recommended
  • Pediatric use: Safety and effectiveness not established
  • Geriatric use: Not indicated for patients 65 years of age and older
  • Severe renal conditions: Contraindicated
  • Moderate to severe hepatic conditions: Contraindicated

Please click here for full Prescribing Information.

Indication and Important Safety Information
 
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Reference: 1. ZELNORM (tegaserod) [package insert]. Covington, LA: Alfasigma USA, Inc. 2019.