Generating signals of drug-adverse effects from prescription databases and application to the risk of arrhythmia associated with antibacterials.
BACKGROUND
Although it is well known that a variety of antibacterials may incidentally cause malignant arrhythmia, the list of drugs causing arrhythmia and the impact of these adverse effects are still uncertain. We investigated on this topic by using a large prescription database with different observational designs.


METHODS
Prescription data on all incident users of several antibacterial and antiarrhythmic drugs over the period July 1997 through December 1999 were retrieved from the Drug Prescription Database (DPD) of the Italian Province of Varese. The association between the use of antibacterial and antiarrhythmic drugs was investigated by applying prescription sequence symmetry, cohort and nested case-control designs.


RESULTS
Lower proarrhythmic effects were on an average obtained from prescription sequence symmetry approach with respect to both cohort and nested case-control. Evidence of association between exposure to drugs (erythromycin and ciprofloxacin) and the risk of arrhythmia was consistently found by the three approaches. No other signals were generated from the prescription sequence symmetry analysis. Two drugs (clarithromycin and levofloxacin) showed patterns compatible with an arrhythmic effect according to both cohort and nested case-control designs.


CONCLUSIONS
Prescription databases are useful tools to explore drug safety through both conventional and emerging observational designs. In spite of its appealing features, prescription sequence symmetry design shows lower sensitivity with respect to conventional designs. Evidence about the association between the use of certain macrolides and fluoroquinolones and the onset of arrhythmia is confirmed by this study.
Corrao
Giovanni
G
Department of Statistics, Unit of Biostatistics, University of Milan-Bicocca, Milan, Italy. giovanni.corrao@unimib.it
Botteri
Edoardo
E
Bagnardi
Vincenzo
V
Zambon
Antonella
A
Carobbio
Alessandra
A
Falcone
Chiara
C
Leoni
Olivia
O
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D002939:Ciprofloxacin / Q000009:adverse effects / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D015331:Cohort Studies; D018672:Community Health Planning / Q000379:methods; D016208:Databases, Factual; D016903:Drug Monitoring / Q000379:methods; D004917:Erythromycin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007558:Italy / Q000453:epidemiology; D064704:Levofloxacin; D015644:Miocamycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009643:Norfloxacin / Q000009:adverse effects / Q000627:therapeutic use; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use; D017891:Pharmacoepidemiology / Q000379:methods; D012307:Risk Factors
D000900:Anti-Bacterial Agents; D015644:Miocamycin; D002939:Ciprofloxacin; D004917:Erythromycin; D064704:Levofloxacin; D015242:Ofloxacin; D017291:Clarithromycin; D009643:Norfloxacin; C033383:rokitamycin