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Proarrhythmia associated with cisapride in children
S L Hill1, J K Evangelista, A M Pizzi
1Division of Pediatric Cardiology, Floating Hospital for Children, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Pediatrics
|June 2, 1998
Summary
Cisapride can prolong ventricular repolarization in children with GERD, increasing arrhythmia risk. Monitor ECG intervals, especially when combined with CYP3A4 inhibitors.
Area of Science:
- Pediatric Cardiology
- Clinical Pharmacology
- Gastroenterology
Background:
- Cisapride is a prokinetic agent used for gastroesophageal reflux disease (GERD).
- Concerns exist regarding cisapride-induced ventricular proarrhythmia, particularly with CYP3A4 inhibitors.
- This study investigates cisapride's impact on ventricular repolarization in pediatric GERD patients.
Purpose of the Study:
- To evaluate the effect of cisapride on ventricular repolarization in children diagnosed with GERD.
- To assess specific electrocardiogram (ECG) parameters related to ventricular repolarization.
Main Methods:
- Prospective, blinded study design.
- Analysis of ECGs from 35 children with GERD treated with cisapride.
- Comparison with ECGs from 1000 healthy children.
- Measurement of QT interval (QTc), JT interval (JTc), and interlead dispersion.
Main Results:
- Prolonged QTc (≥450 ms) observed in 31% of cisapride-treated children.
- Prolonged JTc (≥360 ms) observed in 46% of patients.
- Two cases of torsades de pointes ventricular tachycardia occurred in patients also taking macrolide antibiotics.
- No significant increase in QT or JT dispersion was noted.
Conclusions:
- Cisapride may prolong ventricular repolarization in pediatric patients.
- Increased proarrhythmia risk is associated with CYP3A4 inhibition, overdosage, or decreased clearance.
- ECG monitoring is recommended for children on cisapride, especially with concomitant QT-prolonging medications.