The effect of cisapride on the corrected QT interval and QT dispersion in premature infants

Background: Cisapride is used frequently in premature neonates as a gastroi ntestinal prokinetic drug. Concerns exist, however, about its safety becaus e of its effect on the QT interval. Premature infants could be at higher ri sk for side effects because of their immaturity. This prospective study inv estigated the pharmacokinetics of cisapride and its effects on corrected QT interval (QTc) and QT dispersion in premature infants. Methods: Electrocardiogram examination was performed just before and after 72 hours of treatment with cisapride (0.2 mg/kg per dose, four times daily) in 10 premature infants. Trough and anticipated peak plasma level of cisap ride and norcisapride, were quantified after 72 hours of treatment. Results were compared with a cohort of 41 term infants aged 0 to 3 months receivin g cisapride treatment. Results: The QTc interval increased significantly from 423 ms to 461 ms aft er 72 hours of treatment (P = 0.0007). No effect was seen on QT dispersion (44.3 ins vs. 45.9 ms). The change in QTc interval was inversely related to postnatal age (R-2 = 0.52; P = 0.02), whereas there was no correlation wit h gestational age or plasma levels of cisapride or norcisapride. Trough and anticipated peak plasma levels of cisapride and norcisapride were signific antly higher in the premature infants compared with the term infants aged 0 to 3 months (P < 0.001). Conclusions: Premature infants less than I month of age could be at higher risk for cardiac side effects of cisapride when used in the same dosage as in older infants. The daily dose should be reduced (0.1 mg/kg per dose, max imum four times daily), and the QTc interval should be monitored closely. T he benefits and safety of cisapride in premature infants less than I month of age should be reconsidered.