PEDIATRICS Vol. 101 No. 6 June 1998, pp. 1053-1056
Proarrhythmia Associated With Cisapride in Children
Received Dec 8, 1997; accepted Mar 19, 1998.
,,
From the Divisions of * Pediatric Cardiology and Pediatric
Gastroenterology, Floating Hospital for Children at New England Medical
Center, Tufts University School of Medicine, Boston, Massachusetts.
Background. Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system.
Objective. We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD.
Methods. We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children.
Results. Eleven (31%) of 35 patients receiving cisapride
had a prolonged QTc (
450 ms). The JTc was prolonged 360 ms in 16 of
35 patients (46%). The mean QTc in the cisapride group was 428 ± 35 ms and mean JTc was 336 ± 35 ms. An increased QT or JT dispersion (>70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes
ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were
treated with either cisapride alone or in conjunction with other GERD
agents, such as ranitidine or omeprazole.
Conclusions. Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.
Key words: cisapride, arrhythmia, QT interval, repolarization.
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