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SPA Newsletter.
Effect of cisapride on the QT interval in infants. Khoshoo V, Edell
D, Clarke R Pediatrics 2000;105(2)
Review: The authors of this paper prospectively studied the effect of cisapride on the QT interval of 3-6 month old infants who were being treated for gastroesophageal reflux (GER). Excluded from this analysis were the following types of patients: those with a history of apnea, those with cardiopulmonary, hepatic or renal disease or those who received a macrolide antibiotic or azole antifungal. There were two groups of infants. Group A (60 patients) had a baseline ECG prior to institution of cisapride therapy (1 mg/kg/day in 3 divided doses)as well as two after the medication was begun. Group B (40 patients), who were already on therapy when the study began, had a ECG at one month after initiation of cisapride (0.8-1.1 mg/kg/day in 3 divided doses). Cisapride treatment resulted in a slight increase in the QTc interval. In Group A the baseline QTc interval increased from 390 milliseconds to 400 milliseconds. In Group B, the children who were on cisapride for > 1 month, the QTc interval measured 403 milliseconds. The accepted upper limit of the QTc is 440 milliseconds. There was one child in each group whose QTc measured > 440 milliseconds and the authors report that neither of these infants showed evidence of arrhythmias or conduction defect. The authors point out that their patients were followed closely and none had clinical conditions which would predispose to increased toxicity. None were receiving other drugs which either decrease cytochrome P 450 3A4 levels or which increase the QTc interval. Several case reports and case series have noted the association between cisapride administration, prolongation of the QTc interval and the development of dysrhythmias. The authors point out that most infants who developed arrthymias had other risk factors such as those mentioned above. Based on their study and comments the arrthymia problem appears to be due to one or more of several factors. Either the cisapride dose is too high or the child is receiving other medications which act to inhibit cisapride metabolism or independently increase the QTc interval. Drugs which inhibit the cytochrome P450 3A4 system such as azole antifungals, macrolide antibiotics, protease inhibitors ritonavir or indinavir and certain antidepressants/tranquilizers when given along with cisapride decrease its metabolism leading to higher serum levels. Drugs which independently increase the QTc interval such as quinidine, sotolol and procainamide may have an additive effect in this regard with given with cisapride. When evaluating a child with GER who is being treated, the dose must be carefully checked and other medications reviewed for those listed above which might predisposed the child to arrthymias. Reviewed by: Thomas J Mancuso, MD, FAAP
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