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The Pharmaceutical Journal Vol 265 No 7107 p152
July 29, 2000 Clinical

Cisapride withdrawn because of cardiac side effects

Cisapride (Prepulsid) has been withdrawn from the UK market until further notice because it has been associated with serious cardiovascular side effects. Product licences for the drug were suspended on July 28.
A letter from the Committee on Safety of Medicines, issued on July 19, says that pharmacists should quarantine and return stocks of all products containing cisapride. Prescriptions for the drug should no longer be dispensed and patients should be told to stop taking the drug and to visit their doctor for a review of treatment. No special precautions are necessary when stopping the drug.
An information sheet for patients has been provided with the letter from the CSM and emphasises that there are unlikely to be any long-term effects on the heart resulting from taking cisapride.

cisapride packaging
All cisapride licences have been suspended

QT interval

Cisapride is a motility stimulant that was indicated for the treatment of gastro-oesophageal reflux, gastric stasis and non-ulcer dyspepsia. It can prolong the QT interval, which may lead to life-threatening arrhythmias. Certain medical conditions and concomitant use of other drugs that prolong the QT interval are known to increase this risk. According to the CSM, cisapride has been associated with 386 reports of serious ventricular arrhythmias (including 125 fatalities) and 50 cases of sudden, unexplained death, worldwide. There have been 5 deaths in the UK
Previous efforts to minimise the co-prescribing of cisapride with contraindicated medicines only had a limited effect and serious cardiovascular reactions, including fatalities, continued to be reported, the CSM says. Consequently, the decision was taken to withdraw the licences because the benefits of the drug did not outweigh the risks of treatment.
In a letter to pharmacists, Janssen Cilag, the UK manufacturer of Prepulsid, says that the main area of concern has been the use of cisapride with contraindicated medicines or in patients with "contraindicated morbidities." The company believes that Prepulsid can be used with an acceptable benefit/risk ratio in appropriate patients "when used according to its full labelling."
Professor Roy Pounder (department of medicine, Royal Free hospital) told The Journal on July 21: "The withdrawal of cisapride is a pity because it had a role and there is no other drug that is an obvious replacement, except possibly metoclopramide. I have been prescribing cisapride for many years and my patients have not seemed to have any problems."

Unlicensed use in children

The MCA says that cisapride is prescribed for children, although the drug has never been licensed for use in this group. It recommends that parents presenting prescriptions for cisapride for their children to pharmacists should be given the same instructions as adult patients (ie, to stop the drug and consult their doctor).
Dr John Puntis (consultant paediatric gastroenterologist, Leeds General infirmary) said on July 21 that reflux could be life-threatening in young children and he thought that cisapride was a useful drug for treating the disorder. There was no direct replacement and the alternatives that did exist also had unpleasant side effects. In 1999, the
European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Paediatric Gastroenterology and Nutrition had both published position statements on the use of cisapride in children, he said. Both had concluded that cisapride was safe in all age groups, if used appropriately, and that cardiac adverse events attributable to cisapride were rare.
The CSM says that the suspension of the UK licences will be reassessed once a European review of the risks and benefits of cisapride has been completed.
Further information about the withdrawal of cisapride may be obtained from the Medicines Control Agency (tel 020 7273 0000) or from Janssen Cilag (tel 0800 169 7681).