Non-antiarrhythmic drugs prolonging the QT interval: considerable use in seven countries.
OBJECTIVE
Many drugs belonging to different therapeutic classes appear to share a potentially fatal side-effect: ventricular tachyarrhythmias associated with QT prolongation. The aim of this study was to assess the relevance and the magnitude of the problem in seven countries by grouping all nonantiarrhythmic drugs according to the type of evidence on QT prolongation and analysing their sales data.


METHODS
We divided all nonantiarrhythmic QT-prolonging agents into the following categories (in increasing order of clinical relevance): group A, drugs with published clinical or preclinical evidence on QT prolongation or with relevant official warnings; group B, drugs with published clinical or preclinical evidence; group C, drugs with published clinical evidence; group D, drug with published clinical evidence on torsades de pointes or ventricular arrhythmias associated with QT prolongation; group E, drugs belonging to group D with official warnings. We retrieved 1998 sales data from community pharmacies in seven countries (Australia, Denmark, England, Germany, Greece, Italy and Sweden). Data for individual agents were expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). Overall use in each country was calculated for each drug group. Groups D and E were considered as the most clinically relevant.


RESULTS
Among the 102 nonantiarrhythmic agents meeting at least one of the inclusion criteria, 33 drugs had sales data > or =1 DDD/1000/day and 71 drugs had a use > or =0.1 DDD/1000/day in at least one country. Among the 37 nonantiarrhythmic agents with published reports of ventricular arrhythmias associated with QT prolongation, 12 compounds had sales data > or =1 DDD/1000/day. Total consumption in each country ranged: from 51.9 to 94.7 DDD/1000/day for group A; from 51.6 to 92.7 DDD/1000/day for group B; from 37.1 to 76.6 DDD/1000/day for group C; from 12.9 to 29.1 DDD/1000/day for group D; and from 5.8 to 15.3 DDD/1000/day for group E.


CONCLUSIONS
In spite of wide variations in the sales of individual agents, the overall extent of use of nonantiarrhythmic QT-prolonging drugs was of the same order of magnitude in all countries. The significant use of drugs belonging to categories D and E should prompt careful risk/benefit assessment of each agent.
De Ponti
Fabrizio
F
Department of Pharmacology, University of Bologna, Bologna, Italy. deponti@biocfarm.unibo.it
Poluzzi
Elisabetta
E
Vaccheri
Alberto
A
Bergman
Ulf
U
Bjerrum
Lars
L
Ferguson
John
J
Frenz
Kerry J
KJ
McManus
Peter
P
Schubert
Ingrid
I
Selke
Gisbert
G
Terzis-Vaslamatzis
Georgia
G
Montanaro
Nicola
N
D001315:Australia; D011307:Drug Prescriptions; D017723:Drug Utilization Review; D064420:Drug-Related Side Effects and Adverse Reactions; D005060:Europe; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000209:etiology