The role of cisapride in the treatment of pediatric gastroesophageal reflux

Background: Cisapride is a gastrointestinal prokinetic agent that is used w orldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. Methods: Because of recent concerns about safety, a critical and in-depth a nalysis of all reported adverse events was performed and resulted in the co nclusions and recommendations that follow. Results: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisa pride is given to pediatric patients who can be considered healthy except f or their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceed ing 30 mg/d), no special safety procedures regarding potential cardiac adve rse events are recommended. However, if cisapride is prescribed for patient s who are known to be or are suspected of being at increased risk for drug- associated increases in QTc interval, certain precautions are advisable. Su ch patients include those:(1) with a previous history of cardiac dysrhythmi as, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or di sease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc inter val should be used before initiation of therapy and after 3 days of treatme nt to ascertain whether a cisapride-induced cardiac adverse effect is prese nt, Conclusions: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced dose s. If higher doses than this are given, the precautions above are advisable . In any patient in whom a prolonged QTc interval is found, the dose of cis apride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and t he administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be re started at half dose with control of the QTc interval. Unfortunately, at pr esent, normal ranges of QTc interval in children are unknown. However, a cr itical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater t han 470 milliseconds as outside it.