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Drug Safety
Published in: Drug Safety 6/2013

Open Access 01-06-2013 | Original Research Article

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Authors: Elisabetta Poluzzi, Emanuel Raschi, Ariola Koci, Ugo Moretti, Edoardo Spina, Elijah R. Behr, Miriam Sturkenboom, Fabrizio De Ponti

Published in: Drug Safety | Issue 6/2013

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Abstract

Background

Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden.

Objective

As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs).

Methods

Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://​www.​azcert.​org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011).

Results

Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82–84.60), cyamemazine (11; 15.48, 6.87–34.91), and olanzapine (189; 7.74, 6.45–9.30).

Conclusions

This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk.
Appendix
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Metadata
Title
Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database
Authors
Elisabetta Poluzzi
Emanuel Raschi
Ariola Koci
Ugo Moretti
Edoardo Spina
Elijah R. Behr
Miriam Sturkenboom
Fabrizio De Ponti
Publication date
01-06-2013
Publisher
Springer International Publishing AG
Published in
Drug Safety / Issue 6/2013
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-013-0032-z

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