Publications

Antimicrobials and the Risk of Torsades de Pointes: The Contribution from Data Mining of the US FDA Adverse Event Reporting System  (2010)

Authors:
Poluzzi, E.; Raschi, E.; Motola, D.; Moretti, Ugo; De Ponti, F.
Title:
Antimicrobials and the Risk of Torsades de Pointes: The Contribution from Data Mining of the US FDA Adverse Event Reporting System
Year:
2010
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
No
Name of journal:
Drug Safety
ISSN of journal:
0114-5916
N° Volume:
33
Number or Folder:
4
:
ADIS
Page numbers:
303-314
Keyword:
antimicrobials; torsades de pointes
Short description of contents:
Drug-induced torsades de pointes (TdP) is a complex regulatory and clinical problem due to the rarity of this sometimes fatal adverse event. In this context, the US FDA Adverse Event Reporting System (AERS) is an important source of information, which can be applied to the analysis of TdP liability of marketed drugs. To critically evaluate the risk of antimicrobial-induced TdP by detecting alert signals in the AERS, on the basis of both quantitative and qualitative analyses. Reports of TdP from January 2004 through December 2008 were retrieved from the public version of the AERS. The absolute number of cases and reporting odds ratio as a measure of disproportionality were evaluated for each antimicrobial drug (quantitative approach). A list of drugs with suspected TdP liability (provided by the Arizona Centre of Education and Research on Therapeutics [CERT]) was used as a reference to define signals. In a further analysis, to refine signal detection, we identified TdP cases without co-medications listed by Arizona CERT (qualitative approach). Over the 5-year period, 374 reports of TdP were retrieved: 28 antibacterials, 8 antifungals, 1 antileprosy and 26 antivirals were involved. Antimicrobials more frequently reported were levofloxacin (55) and moxifloxacin (37) among the antibacterials, fluconazole (47) and voriconazole (17) among the antifungals, and lamivudine (8) and nelfinavir (6) among the antivirals. A significant disproportionality was observed for 17 compounds, including several macrolides, fluoroquinolones, linezolid, triazole antifungals, caspofungin, indinavir and nelfinavir. With the qualitative approach, we identified the following additional drugs or fixed dose combinations, characterized by at least two TdP cases without co-medications listed by Arizona CERT: ceftriaxone, piperacillin/tazobactam, cotrimoxazole, metronidazole, ribavirin, lamivudine and lopinavir/ritonavir. Disproportionality for macrolides, fluoroquinolones and most of the azole antifungals should be viewed as 'expected' according to Arizona CERT list. By contrast, signals were generated by linezolid, caspofungin, posaconazole, indinavir and nelfinavir. Drugs detected only by the qualitative approach should be further investigated by increasing the sensitivity of the method, e.g. by searching also for the TdP surrogate marker, prolongation of the QT interval. The freely available version of the FDA AERS database represents an important source to detect signals of TdP. In particular, our analysis generated five signals among antimicrobials for which further investigations and active surveillance are warranted. These signals should be considered in evaluating the benefit-risk profile of these drugs.
Web page:
http://dx.doi.org/10.2165/11531850-000000000-00000
Product ID:
55481
Handle IRIS:
11562/341178
Deposited On:
April 26, 2010
Last Modified:
April 14, 2023
Bibliographic citation:
Poluzzi, E.; Raschi, E.; Motola, D.; Moretti, Ugo; De Ponti, F., Antimicrobials and the Risk of Torsades de Pointes: The Contribution from Data Mining of the US FDA Adverse Event Reporting System «Drug Safety» , vol. 33 , n. 42010pp. 303-314

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Potenziale aritmogenico dei farmaci (ARITMO) Department Diagnostica e Sanità Pubblica Ugo Moretti
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