Article Text

Risks and benefits of cisapride
  1. STEPHEN W JONES, Consultant Paediatrician and Neonatologist,
  1. Royal United Hospital, Bath BA1 3NG, UK
    1. MILES WAGSTAFF, Specialist Registrar in Paediatrics
    1. Royal United Hospital, Bath BA1 3NG, UK

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      Editor,—Following the recent warnings against the use of cisapride in children from the Medicines Control Agency and the Committee on Safety of Medicines (CSM),1 we felt that the recent annotation by Lander and Desai2 was unwise. While it is right to question advice from the CSM, we feel it is more appropriate to do this in a personal practice article, and accompany it with a commentary.

      Lander dismisses concerns about cisapride by saying they have not seen abnormalities of QTc in their series of 17 patients, as well as by quoting a study in which only two of 35 patients developed life threatening arrhythmias.3 These studies are small and statistically unsound, but they do show us an unacceptably high risk when using cisapride; one of our patients suffered sudden infant death one week after starting cisapride, an event we obviously reported to the CSM. Lander and Desai also suggest measuring QTc before and after starting treatment, but our recent experience of a regional neonatal unit surgical patient showed that not all doctors can measure QTc accurately, making this safeguard inadequate.

      We agree there is evidence that cisapride reduces the incidence and severity of gastro-oesophageal reflux in some circumstances. However, we also agree with the CSM, which advises that it is unsafe to prescribe a drug with the potential side effect of sudden death when there are alternatives. We are concerned that this second, safer point of view, even if published as a letter, will have less impact than an annotation.


      Dr Lander comments:

      We raised two issues: first, the CSM claimed insufficient data supported the use of cisapride in children younger than 12 years.1-1 Our review did not support this so we asked the CSM to clarify their reasoning; second, the CSM contraindicated cisapride in infants < 36 weeks’ gestation for 3 months after birth. We did not advocate against this contraindication but questioned the evidence for it. We believe that in a correct dose and avoiding interfering drugs, cisapride may be safe and useful, it would be wrong to contraindicate it without good evidence.

      Although we abide by the CSM’s contraindication, many neonatologists still use cisapride in preterm infants. Ward et alfound cisapride use in infants < 36 weeks’ gestation and < 3 months of age to be widespread in the USA.1-2 Adverse events occurred only with very high doses or in combination with drugs inhibiting cisapride metabolism. Arrhythmias were reported in fewer than 1/11 000 treated premature babies, further encouraging us to think that the issue of prematurity should be revisited by the CSM.

      Jones and Wagstaff are right that QTc is not simple to measure and it varies between leads. We have looked at the QTc estimated in different leads of a given ECG. The difference between the largest and smallest QTc in a given ECG is the QTc dispersion. The values of QTc dispersion show intraobserver and interobserver variation, making analysis difficult; however, the mean QTc across a number of leads does not appear to rise significantly on cisapride but the dispersion decreases. Cisapride seems to raise the shortest QTc more than the longest.

      In clinical practice, a simple estimate of QTc should establish whether a child has a pathologically prolonged QT interval, indicating that cisapride should be avoided.


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