Oral domperidone exposure was significantly associated with an increased odds of ventricular arrhythmia (aOR 1.56; 95% CI 1.41-1.72), with higher risk at doses >30 mg and with concomitant CYP 3A4 inhibitors.
Case-Control (n=25,356)
Does oral domperidone, alone or with CYP 3A4 inhibitors, increase the risk of ventricular arrhythmia?
Oral domperidone use, particularly at doses >30 mg/day or when combined with CYP 3A4 inhibitors, is associated with a significantly increased risk of ventricular arrhythmia.
Odds Ratio: 1.56 (95% CI 1.41–1.72)
BACKGROUND: Recent evidence suggested that oral form of domperidone may possess pro-arrhythmic effects and increase the risk of ventricular arrhythmia. The concomitant use of cytochrome P450 (CYP) 3A4 isoenzyme inhibitors may further potentiate this association. Nevertheless, empirical data supporting these associations are very limited. The aim of this study was to investigate the association between oral domperidone, CYP 3A4 inhibitors, and ventricular arrhythmia. METHODS: We identified 25,356 patients who were admitted or were seen in the emergency room for ventricular arrhythmia between 2000 and 2011 from Taiwan's Longitudinal Health Insurance Database. We adopted a case-crossover study design to compare the exposure to oral domperidone for the same patient within a "case period" and within a "control period". RESULTS: Conditional logistic regression models showed that domperidone use was significantly associated with an increased odds of ventricular arrhythmia (aOR 1.56, 95%CI 1.41-1.72). The association was stronger with a higher daily dose of domperidone (>30 mg, aOR 1.98, 95%CI 1.50-2.63). Furthermore, the co-exposure of domperidone and CYP 3A4 inhibitors was significantly associated with an increased odds of ventricular arrhythmia, especially considering the lasting effect of CYP 3A4 inhibitors (1 day apart: aOR 1.91, 95%CI 1.33-2.75, 3 days apart: aOR 1.90, 95%CI 1.33-2.71, 7 days apart: aOR 1.80, 95%CI 1.28-2.54). CONCLUSIONS: Our results suggested that oral domperidone was significantly associated with an increased odds of ventricular arrhythmia and that the association was stronger with exposure to >30 mg of domperidone. In addition, our study reported increased odds of ventricular arrhythmia among those who concomitantly used domperidone and CYP 3A4 inhibitors.
Chen et al. (Mon,) conducted a case-control in Ventricular arrhythmia (n=25,356). Oral domperidone vs. Control period (same patient) was evaluated on Ventricular arrhythmia (aOR 1.56, 95% CI 1.41-1.72). Oral domperidone exposure was significantly associated with an increased odds of ventricular arrhythmia (aOR 1.56; 95% CI 1.41-1.72), with higher risk at doses >30 mg and with concomitant CYP 3A4 inhibitors.
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