Pharmacy World and Science

, Volume 15, Issue 5, pp 212–218 | Cite as

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
  • Ron M. C. Herings
  • Bruno H. Ch. Stricker
  • Hubert G. M. Leufkens
  • Albert Bakker
  • Ferd Sturmans
  • John Urquhart


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.


Adverse effects Astemizole Drug interactions Overdose Probability Product surveillance, postmarketing Terfenadine Torsades de pointes 


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Copyright information

© Periodicals Service Company 1993

Authors and Affiliations

  • Ron M. C. Herings
    • 1
  • Bruno H. Ch. Stricker
    • 2
  • Hubert G. M. Leufkens
    • 1
  • Albert Bakker
    • 1
  • Ferd Sturmans
    • 3
  • John Urquhart
    • 3
  1. 1.Department of Pharmacoepidemiology and Pharmacotherapy, Faculty of PharmacyUtrecht UniversityTB Utrechtthe Netherlands
  2. 2.Department of Internal Medicine II, Pharmacoepidemiology UnitErasmus University RotterdamGD Rotterdamthe Netherlands
  3. 3.Department of Epidemiology, Faculty of MedicineLimburg UniversityMD Maastrichtthe Netherlands

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