Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS).
OBJECTIVE
To investigate spontaneous reports of TdP present in the public version of the FDA Adverse Event Reporting System (AERS) in the light of what is already known on their TdP-liability.


METHODS
Reports of TdP from January 2004 through December 2007 were retrieved from the public version of the AERS database. All reports were selected from REACTION files and the relevant suspected and/or interacting drugs were identified from DRUG files. Qualitative analysis was performed by the case/non-case method. Cases were represented by TdP reports, whereas non-cases were all reports of adverse drug reactions other than TdP. Quantitative analysis was assessed by calculating the crude and adjusted reporting odds ratio (ROR), as a measure of disproportionality, with the 95% confidence interval.


RESULTS
Reports of TdP were 1665 over a 4-year period, involving 376 active substances. Thirty-five drugs with at least 10 reports were identified: amiodarone and methadone were associated with the highest number of cases (113 and 83 respectively) and most of the other reports were ascribable to antibacterials, antidepressants and antipsychotics; remarkable differences in number of cases and ROR were present among agents within each therapeutic class. A disproportionate reporting was also observed for other compounds such as donepezil, famotidine and mitoxantrone.


CONCLUSIONS
Large spontaneous reporting databases represent an important source for signal detection of rare adverse drug reactions (ADR), such as TdP. The number of reports associated to donepezil, famotidine and mitoxantrone could be considered unexpected on the basis of current evidence and needs further investigations on their true TdP-liability.
Department of Pharmacology, University of Bologna, Bologna, Italy.
Elisabetta
E
Poluzzi
Emanuel
E
Raschi
Ugo
U
Moretti
Fabrizio
F
De Ponti
D016907:Adverse Drug Reaction Reporting Systems; D000638:Amiodarone / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000928:Antidepressive Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000009:adverse effects; D016208:Databases, Factual / Q000706:statistics & numerical data*; D000077265:Donepezil; D015738:Famotidine / Q000009:adverse effects; D006801:Humans; D007189:Indans / Q000009:adverse effects; D008691:Methadone / Q000009:adverse effects; D008942:Mitoxantrone / Q000009:adverse effects; D010880:Piperidines / Q000009:adverse effects; D016171:Torsades de Pointes / Q000139:chemically induced*; D014481:United States; D014486:United States Food and Drug Administration
D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002317:Cardiovascular Agents; D007189:Indans; D010880:Piperidines; D015738:Famotidine; D000077265:Donepezil; D008942:Mitoxantrone; D000638:Amiodarone; D008691:Methadone