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Drug Safety

, Volume 33, Issue 11, pp 1003–1014 | Cite as

Domperidone and Ventricular Arrhythmia or Sudden Cardiac Death

A Population-Based Case-Control Study in the Netherlands
  • Charlotte van Noord
  • Jeanne P. Dieleman
  • Gerard van Herpen
  • Katia Verhamme
  • iriam C. J. M. Sturkenboom
Original Research Article

Abstract

Background: Recently, a 4-fold increase in risk of sudden cardiac death (SCD) was reported for domperidone in a study that focused on corrected QT interval (QTc)-prolonging drugs as a class and their association with SCD.

Objective: To evaluate the association between the use of domperidone and serious non-fatal ventricular arrhythmia (VA) and SCD in the general population.

Methods: We performed a population-based, case-control study during 1996–2007 in the Integrated Primary Care Information (IPCI) database, a longitudinal general practice research database in the Netherlands. We included all patients aged ≥18 years without cancer in the source population. We studied the association between the use of domperidone by recency of use (current, past and none) and daily dose, and the risk of serious non-fatal VA or SCD. Cases were defined as a natural death due to cardiac causes heralded by abrupt loss of consciousness within 1 hour after the onset of acute symptoms or an unwitnessed, unexpected death of someone seen in a stable medical condition <24 hours previously with no evidence of a non-cardiac cause. Controls were randomly drawn from the source population and matched to cases on age, sex, practice and index date. We compared the exposure odds for SCD alone and VA plus SCD by means of conditional logistic regression while adjusting for all available confounders. In addition, we stratified by insurance type.

Results: The study population comprised 1366 cases (62 VA and 1304 SCD) and 14114 matched controls. Of all cases, ten patients were current domperidone users at the index date, all with SCD. The matched unadjusted odds ratio of domperidone and SCD was 3.72 (95% CI 1.72, 8.08). Daily doses >30 mg were associated with a significant increased risk of SCD (adjusted odds ratio [ORadj] 11.4 [95% CI 1.99, 65.2]). Since there was a near interaction with health insurance (p = 0.050), all analyses were stratified by insurance. In publicly insured patients, seven cases were current users at the index date. Current use was associated with a significant increased risk of SCD (ORadj 4.17 [95% CI 1.33, 13.1]). Amongst privately insured patients there was one domperidone-exposed case, and amongst non-insured there were two.

Conclusions: Current use of domperidone, especially high doses, is associated with an increased risk of SCD. We could not demonstrate an effect of domperidone on non-fatal VA due to absence of exposed cases.

Keywords

Ventricular Arrhythmia Sudden Cardiac Death Index Date Domperidone Healthcare Insurance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was partially sponsored by an unrestricted grant to the Integrated Primary Care Information (IPCI) database from Johnson & Johnson.

Charlotte van Noord also works as a pharmacovigilance assessor at the Dutch Medicines Evaluation Board. As an employee of Erasmus MC, Miriam Sturkenboom has been involved as a project leader and in analyses contracted by various pharmaceutical companies, and received unconditional research grants from Pfizer, Merck, Johnson & Johnson, Amgen, Roche, GlaxoSmithKline, Boehringer, Yamanouchi and Altana, none of which are related to the subject of this study. Miriam Sturkenboom has been a consultant to Pfizer, Servier, Celgene, Novartis and Lundbeck on issues not related to this study. As an employee of the IPCI, Jeanne P. Dieleman has received grants from pharmaceutical companies, including Johnson & Johnson, for the conduct of epidemiological studies. Katia Verhamme has received grants unrelated to this study from Yamanouchi, Boehringer Ingleheim and Pfizer. Gerard van Herpen has no conflict of interest to declare.

The study is an accurate representation of the study results.

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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Charlotte van Noord
    • 1
  • Jeanne P. Dieleman
    • 1
  • Gerard van Herpen
    • 1
  • Katia Verhamme
    • 1
  • iriam C. J. M. Sturkenboom
    • 1
  1. 1.Department of Medical InformaticsErasmus Medical CenterRotterdamthe Netherlands

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