title: 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.
abstract: Recently, the use of astemizole and terfenadine, both non-sedating H1-antihistamines, caused considerable concern. Several case reports suggested an association of both drugs with an increased risk of torsades de pointes, a special form of ventricular tachycardia. The increased risk of both H1-antihistamines was associated with exposure to supratherapeutic doses; for terfenadine the risk was also associated with concomitant exposure to the cytochrome P-450 inhibitors ketoconazole, erythromycin 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 inhibitors was studied. Data were obtained from the PHARMO data base in 1990, a pharmacy-based record linkage system encompassing a catchment population 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 torsades de pointes has to be as high as 1 in 10,000 to cause one death in the Netherlands in one year.
authors.affiliation: Department of Pharmacoepidemiology and Pharmacotherapy, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Herings
authors.forename: B H
authors.initials: BH
authors.lastname: Stricker
authors.forename: H G
authors.initials: HG
authors.lastname: Leufkens
authors.forename: A
authors.initials: A
authors.lastname: Bakker
authors.forename: F
authors.initials: F
authors.lastname: Sturmans
authors.forename: J
authors.initials: J
authors.lastname: Urquhart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016589:Astemizole / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004357:Drug Synergism; D004363:Drug Utilization; D006801:Humans; D015994:Incidence; D007223:Infant; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012307:Risk Factors; D016593:Terfenadine / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D016593:Terfenadine; D016589:Astemizole