PUBLIC-HEALTH PROBLEMS AND THE RAPID ESTIMATION OF THE SIZE OF THE POPULATION AT RISK - TORSADES-DE-POINTES AND THE USE OF TERFENADINE AND ASTEMIZOLE IN THE NETHERLANDS

Recently, the use of astemizole and terfenadine, both non-sedating H-1 -antihistamines, caused considerable concern. Several case reports sug gested an association of both drugs with an increased risk of torsades de pointes, a special form of ventricular tachycardia. The increased risk of both H-1-antihistamines was associated with exposure to suprat herapeutic doses; for terfenadine the risk was also associated with co ncomitant exposure to the cytochrome P-450 inhibitors ketoconazole, er ythromycin and cimetidine. To predict the size of the population that runs the risk of developing this potentially fatal adverse reaction in the Netherlands, the prevalence of prescribing supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhi bitors was studied. Data were obtained from the PHARMO data base in 19 90, a pharmacy-based record linkage system encompassing a catchment po pulation of 300,000 individuals. The results of the study showed that the prescribing of supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhibitors was low. Furthermore, the results of a sensitivity analysis showed that the risk of fatal to rsades de pointes has to be as high as 1 in 10,000 to cause one death in the Netherlands in one year.