Exposure to antibacterial agents with QT liability in 14 European countries: trends over an 8-year period

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Several noncardiovascular drugs with QT liability are currently on the market. center dot Previous epidemiological studies have shown significant exposure of the general population to drugs with QT liability with similar consumption in many European countries. center dot Several regulatory measures have concerned medicinal products carrying a pro-arrhythmic risk in humans. WHAT THIS STUDY ADDS center dot The list of antibacterial agents with documented QT liability has grown over the last few years. center dot Notwithstanding stringent regulatory measures, population exposure to antibiotics with QT liability is still significant in several countries. center dot The magnitude of the problem is clearly heterogeneous, with remarkable diversity between Northern and Southern countries (lower and higher exposure, respectively). (i) To classify antibacterial agents with QT liability on the basis of the available evidence, and (ii) to assess trends in their consumption over an 8-year period (1998-2005) in 14 European countries. Current published evidence on QT liability of antibiotics was retrieved through MEDLINE search and joined to official warnings from regulatory agencies. Each drug was classified according to an already proposed algorithm based on the strength of evidence: from group A (any evidence) to group E (clinical reports of torsades de pointes and warnings on QT liability). Consumption data were provided by the European Surveillance of Antibacterial Consumption (ESAC) project and were expressed as defined daily doses per 1000 inhabitants per day (DID). Among 21 detected compounds, nine [six fluoroquinolones (FQs) and three macrolides (MACs)] belonged to group E. Use of group E drugs ranged from 1.3 (Sweden) to 4.1 DID (Italy) in 1998 and from 1.2 (Sweden) to 6.5 DID (Italy) in 2005. Significant exposure was observed in Italy and Spain (6.5 and 3.8 DID, respectively, in 2005). Only Denmark, Sweden and UK showed a slight decrease in use. Exposure to clarithromycin increased in 10 out of 14 countries, with a marked increment in Italy (3 DID in 2005). Notwithstanding regulatory measures, in 2005 there was still significant exposure to antibacterials with strong evidence of QT liability and, in most countries, it was even increased. This warrants further investigation of appropriateness of use and suggests closer monitoring of group E drugs. Physicians should be aware when prescribing them to susceptible patients.