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

Authors :
Fabrizio De Ponti
Ariola Koci
Edoardo Spina
Emanuel Raschi
Ugo Moretti
Elijah R. Behr
Elisabetta Poluzzi
Miriam C. J. M. Sturkenboom
Poluzzi E
Raschi E
Koci A
Moretti U
Spina E
Behr ER
Sturkenboom M
De Ponti F
Medical Informatics
Source :
Drug Safety, Drug Safety, 36(6), 467-479. Adis, Drug Safety; Vol 36
Publication Year :
2013

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. Electronic supplementary material The online version of this article (doi:10.1007/s40264-013-0032-z) contains supplementary material, which is available to authorized users.

Details

ISSN :
01145916
Volume :
36
Issue :
6
Database :
OpenAIRE
Journal :
Drug Safety
Accession number :
edsair.doi.dedup.....a4f9bd17b1886dff64ae384edd0c3b95
Full Text :
https://doi.org/10.1007/s40264-013-0032-z