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Tegaserod (United States: Withdrawn from market): Drug information

Tegaserod (United States: Withdrawn from market): Drug information
(For additional information see "Tegaserod (United States: Withdrawn from market): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Zelnorm New Drug Application (NDA) Withdrawn from US Market July 2022

The manufacturer of Zelnorm (tegaserod), Alfasigma USA, has announced the voluntary withdrawal of the Zelnorm NDA from the US market effective June 30, 2022. Alfasigma USA stated the decision was not based on product efficacy, safety, or because of an imposed recall. Patients will have access to the existing supply of Zelnorm until it is depleted. Patients and health care providers should discuss alternative therapies.

Further information may be found at https://www.myzelnorm.com/assets/pdfs/Press%20Release%20on%20Notice%20of%20Withdrawal.pdf and https://www.myzelnorm.com/assets/pdfs/Zelnorm%20FAQS.pdf.

Brand Names: US
  • Zelnorm [DSC]
Pharmacologic Category
  • Gastrointestinal Agent, Prokinetic;
  • Serotonin 5-HT4 Receptor Agonist
Dosing: Adult
Irritable bowel syndrome with constipation

Irritable bowel syndrome with constipation: Females <65 years of age:

Note: The American College of Gastroenterology guideline for the management of irritable bowel syndrome recommends against use in women with more than one cardiac risk factor. Risk factors include history of cardiovascular disease, hypertension, diabetes or hyperlipidemia, active smoking, age >55 years, or BMI >30 kg/m2 (ACG [Lacy 2021]).

Oral: 6 mg twice daily; discontinue use in patients with an inadequate response after 4 to 6 weeks of treatment.

Dosing: Kidney Impairment: Adult

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

eGFR ≥15 to <30 mL/minute/1.73 m2: There are no specific dosage adjustments provided in the manufacturer’s labeling; use with caution.

eGFR <15 mL/minute/1.73 m2: Use is contraindicated.

End-stage renal disease on hemodialysis: Use is contraindicated.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate to severe impairment (Child-Pugh class B or C): Use is contraindicated.

Dosing: Older Adult

Use in elderly women (≥65 years of age) is contraindicated.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Zelnorm: 6 mg [DSC]

Generic Equivalent Available: US

No

Administration: Adult

Administer ≥30 minutes before meals.

Use: Labeled Indications

Irritable bowel syndrome with constipation: Treatment of irritable bowel syndrome (IBS) with constipation in women (<65 years of age).

Limitations of use: The American College of Gastroenterology guideline for the management of IBS recommends against use in women with more than one cardiac risk factor. Risk factors include history of cardiovascular disease, hypertension, diabetes or hyperlipidemia, active smoking, age >55 years, or BMI >30 kg/m2 (ACG [Lacy 2021]).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Headache (14%)

Gastrointestinal: Abdominal pain (11%)

1% to 10%:

Central nervous system: Dizziness (4%), migraine (≤2%), vertigo (≤2%)

Gastrointestinal: Diarrhea (8%), nausea (8%), flatulence (6%), dyspepsia (4%), increased appetite (≤2%)

Hematologic & oncologic: Anemia (≤2%), rectal hemorrhage (≤2%)

Neuromuscular & skeletal: Arthropathy (≤2%), asthenia (≤2%), increased creatine phosphokinase in blood specimen (≤2%), tendinopathy (≤2%)

<1%: Suicidal ideation, suicidal tendencies

Postmarketing: Acute myocardial infarction, alopecia, anaphylaxis, cerebrovascular accident, cholecystitis, choledocholithiasis, hepatitis, hypersensitivity reaction, increased serum alanine aminotransferase, increased serum aspartate transaminase, increased serum bilirubin, intestinal necrosis (gangrenous bowel), ischemic colitis, mesenteric ischemia, severe diarrhea, spasm of sphincter of Oddi

Contraindications

Hypersensitivity to tegaserod or any component of the formulation; severe renal impairment (eGFR <15 mL/minute/1.73 m2) or end-stage renal disease; moderate or severe hepatic impairment (Child-Pugh class B or C); history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions; history of ischemic colitis or other forms of intestinal ischemia; history of myocardial infarction, stroke, transient ischemic attack, or angina

Warnings/Precautions

Concerns related to adverse reactions:

• Cardiovascular effects: Serious cardiovascular events (eg, myocardial infarction [MI], stroke, cardiovascular death) have been reported in patients with cardiovascular risk factors (eg, smoker, hypertension, hyperlipidemia, diabetes, obesity). Use is contraindicated in patients with a history of MI, stroke, transient ischemic attack (TIA), or angina. Discontinue use if MI, stroke, TIA, or angina occur.

• Diarrhea: Diarrhea can occur; serious consequences of diarrhea (hypovolemia, hypotension, syncope) have also been reported and may require hospitalization for rehydration. Avoid use in patients who are currently experiencing or frequently experience diarrhea. Patients should discontinue use and contact health care provider if severe diarrhea, hypotension, or syncope occur.

• Intestinal ischemic events: Use has been associated with ischemic colitis and other forms of intestinal ischemia. Discontinue immediately with new or sudden worsening abdominal pain, bloody diarrhea, or rectal bleeding; do not reinitiate therapy if ischemic colitis is diagnosed.

• Suicidal ideation/behavior: Suicide, suicide attempts and ideation, and self-injury have been reported. Closely monitor patients for worsening of depression or the emergence of suicidal thoughts and behaviors, especially in the first few months of therapy; discontinue therapy immediately for any symptoms.

Special populations:

• Elderly women: Not indicated in women ≥65 years of age.

• Males: Safety and efficacy have not been established in males.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Anticholinergic Agents: May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Fosfomycin: Gastrointestinal Agents (Prokinetic) may decrease the serum concentration of Fosfomycin. Risk C: Monitor therapy

Opioid Agonists: May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Tegaserod. Risk C: Monitor therapy

Sirolimus (Conventional): Gastrointestinal Agents (Prokinetic) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Food Interactions

Bioavailability is decreased by 40% to 65% and Cmax is decreased by 20% to 40% when taken with food. Tmax is prolonged from 1 hour up to 2 hours when taken following a meal, but decreased to 0.7 hours when taken 30 minutes before a meal. Management: Take on an empty stomach 30 minutes before meals.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Pregnant women were excluded from clinical trials and outcome information following inadvertent pregnancy exposure is limited (Appel-Dingemanse 2002).

Breastfeeding Considerations

It is not known if tegaserod is present in breast milk.

Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer.

Dietary Considerations

Take ≥30 minutes before meals.

Mechanism of Action

Tegaserod is a partial neuronal 5-HT4 receptor agonist. Its action at the receptor site leads to stimulation of the peristaltic reflex and intestinal secretion, and moderation of visceral sensitivity.

Pharmacokinetics

Distribution: Vd: 368 ± 223 L

Protein binding: 98% primarily to α1-acid glycoprotein

Metabolism: GI: Hydrolysis in the stomach; Hepatic: Oxidation, conjugation, and glucuronidation; metabolite (negligible activity); significant first-pass effect

Bioavailability: Fasting: 10%

Half-life elimination: Terminal: 4.6 to 8.1 hours

Time to peak: ~1 hour

Excretion: Feces (~66% as unchanged drug); urine (~33% as metabolites)

Pharmacokinetics: Additional Considerations

Altered kidney function: Pharmacokinetics of tegaserod are not altered in renal impairment; however, the main metabolite (M29) Cmax is doubled and AUC is increased 10-fold in severe impairment (eGFR <15 mL/minute/1.73 m2) compared to subjects with normal renal function.

Hepatic function impairment: Mean tegaserod AUC is increased 31% and Cmax is increased 16% in mild impairment versus normal hepatic function. Has not been studied in moderate or severe impairment, although in a single report of moderate impairment the Cmax and AUC were 140% and 200%, respectively, of that observed in healthy controls.

Pricing: US

Tablets (Zelnorm Oral)

6 mg (per each): $9.01

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Colonaid (CL, PY);
  • Coloserod (AR, UY);
  • Gasprid (CO);
  • Tegarod (AR);
  • Zelmac (AE, AR, AU, BR, CH, CN, CZ, EC, HK, ID, KR, MX, MY, NZ, PE, PK, SA, SG, TH, TW, VE, VN);
  • Zelnorm (PH);
  • Zerada (CR, DO, GT, HN, NI, PA, SV)


For country code abbreviations (show table)
  1. Appel-Dingemanse S. Clinical pharmacokinetics of tegaserod, a serotonin 5-HT(4) receptor partial agonist with promotile activity. Clin Pharmacokinet. 2002;41(13):1021-1042. [PubMed 12403641]
  2. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44. doi:10.14309/ajg.0000000000001036 [PubMed 33315591]
  3. Zelnorm (tegaserod) [prescribing information]. Covington, LA: Alfasigma USA Inc; June 2020.
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