title: Domperidone, cytochrome P450 3A4 isoenzyme inhibitors and ventricular arrhythmia: a nationwide case-crossover study.
abstract: 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.
authors.affiliation: Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hung-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.|School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Fei-Yuan
authors.initials: FY
authors.lastname: Hsiao
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D018592:Cross-Over Studies; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000009:adverse effects*; D016208:Databases, Factual; D004294:Domperidone / Q000008:administration & dosage / Q000009:adverse effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017891:Pharmacoepidemiology; D019338:Polypharmacy; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D018492:Dopamine Antagonists; D004294:Domperidone
keywords: Longitudinal Health Insurance Database; case-crossover study; domperidone; pharmacoepidemiology; ventricular arrhythmia