DIQTA 1.0: Drug-Induced QT Prolongation Atlas

TEGASEROD

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Ambiguous

Severity Score:1.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
Centrally analyzed ECGs were recorded in 4,605 male and female patients receiving ZELNORM 6 mg twice daily or placebo for IBS-C and other related motility disorders. No subject receiving tegaserod had an absolute QTcF above 480 ms. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving ZELNORM and 8% receiving placebo. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively. The effects of tegaserod on the QTcF interval were not considered to be clinically meaningful.
NONCLINICAL TOXICOLOGY
Animal Toxicology and/or Pharmacology
Inhibition of the hERG (human Ether-a-go-go-Related Gene) channel was evident only in the micromolar concentration range with an IC50 of 13 micromolar (approximately 1300 times the Cmax in humans at the recommended dose). In in vitro studies, tegaserod had no effects on impulse conduction in isolated guinea pig papillary muscle at up to 100 times the Cmax in humans, Langendorff-perfused isolated rabbit heart (QT interval) at up to 1000 times the Cmax in humans, or human atrial myocytes at multiples up to 10 times the Cmax in humans. The major metabolite, M29, had no effect on QT in the Langendorff-perfused isolated rabbit heart at multiples up to 323 times the Cmax in humans.
In anesthetized and conscious dogs, tegaserod at doses up to 92 to 134 times the recommended dose based on Cmax did not alter heart rate, QRS interval duration, QTc or other ECG parameters. In chronic toxicology studies in rats and dogs, there were no treatment-related changes in cardiac morphology after tegaserod administration at doses up to 660 times the recommended dose based on AUC.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24087

Other ADRs

15918

38365669

Odds Ratio = 0.501

Drug Property Information

ATC Code(s):

A06AX06 - tegaserod

A06AX - Other laxatives
A06A - LAXATIVES
A06 - LAXATIVES
A - ALIMENTARY TRACT AND METABOLISM

Active Ingredient:TEGASEROD

Active Ingredient UNII:458VC51857

Drugbank ID:DB01079

PubChem Compound:5362436

CTD ID:C105050

PharmGKB:PA130413154

CAS Number:145158-71-0

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

12.0 mg/day A06AX06

Chemical Structure:

SMILE Code:
CCCCCNC(=N)N\N=C\C1=CNC2=C1C=C(OC)C=C2

Reference

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Clin Pharmacol Drug Dev,2020 Nov;9(8):938-951. PMID: 32087003

2: {'sub': '4', '#text': 'The in vitro pharmacology and non-clinical cardiovascular safety studies of a novel 5-HT receptor agonist, DSP-6952.'}

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Eur J Pharmacol,2018 May 5;826:96-105. PMID: 29501863

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[Tack J,Camilleri M,Chang L,Chey W D,Galligan J J,Lacy B E,Müller-Lissner S,Quigley E M M,Schuurkes J,De Maeyer J H,Stanghellini V]
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[Kamm Michael A]
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[Kamm M A]
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6: Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart.

[Drici M D,Ebert S N,Wang W X,Rodriguez I,Liu X K,Whitfield B H,Woosley R L]
J Cardiovasc Pharmacol,1999 Jul;34(1):82-8. PMID: 10413072

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