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 14 114 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.

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Drug Safety
Department of Medical Informatics

van Noord, C., Dieleman, J., van Herpen, G., Verhamme, K., & Sturkenboom, M. (2010). Domperidone and ventricular arrhythmia or sudden cardiac death: A population-based case-control study in the Netherlands. Drug Safety, 33(11), 1003–1014. doi:10.2165/11536840-000000000-00000