Vandenplas Y, Belli D C, Benatar A, Cadranel S, Cucchiara S, Dupont C, Gottrand F, Hassall E, Heymans H S, Kearns G, Kneepkens C M, Koletzko S, Milla P, Polanco I, Staiano A M
AZ-VUB, Brussels, Belgium.
J Pediatr Gastroenterol Nutr. 1999 May;28(5):518-28. doi: 10.1097/00005176-199905000-00017.
Cisapride is a gastrointestinal prokinetic agent that is used worldwide 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.
Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow.
Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for 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 exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present.
With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. 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 cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.
西沙必利是一种胃肠促动力剂，在全球范围内用于治疗早产儿、足月儿及儿童的胃肠动力相关疾病。疗效数据表明，它是市面上最有效的促动力药物。
鉴于近期对安全性的担忧，对所有报告的不良事件进行了严格且深入的分析，并得出了以下结论和建议。
西沙必利仅应给予根据当前医学知识使用促动力剂合理的患者。如果将西沙必利给予除胃肠动力障碍外可视为健康的儿科患者，且最大剂量不超过每日0.8毫克/千克，分3至4次给药，每次0.2毫克/千克（不超过40毫克/天），则不建议针对潜在心脏不良事件采取特殊安全措施。然而，如果为已知或疑似药物相关QTc间期延长风险增加的患者开具西沙必利处方，则建议采取某些预防措施。此类患者包括：（1）有心脏心律失常病史者；（2）正在接受已知会抑制西沙必利代谢和/或对心室复极产生不利影响的药物者；（3）因不成熟和/或疾病导致细胞色素P450 3A4活性降低者；或（4）有电解质紊乱者。对于此类患者，应在治疗开始前和治疗3天后进行心电图监测以定量QTc间期，以确定是否存在西沙必利引起的心脏不良反应。
除极少数情况外，西沙必利的每日总剂量不应超过0.8毫克/千克，分为3或4次大致等间隔给药。如果给予高于此剂量的药物，则建议采取上述预防措施。在任何发现QTc间期延长的患者中，应减少西沙必利剂量或停药，直至心电图恢复正常。如果停用西沙必利后QTc间期恢复正常，且由于其疗效且无替代治疗选择而认为给予西沙必利合理，则可在控制QTc间期的情况下以半剂量重新开始使用西沙必利。不幸的是，目前儿童QTc间期的正常范围尚不清楚。然而，对文献的严格分析表明，持续时间小于450毫秒可被视为在正常范围内，大于470毫秒则超出正常范围。
