Cisapride

The product licence for cisapride (Prepulsid), a drug used to treat gastric and digestive disorders in adults and children, has been suspended by the Medicines Control Agency after five deaths in the United Kingdom and 125 deaths worldwide that are thought to be associated with the drug.

When the Committee on Safety of Medicines recently reviewed the drug, which is made by Janssen-Cilag, it found rare but serious disturbances in heart rhythm associated with it.

Since 1988, when cisapride was licensed in the United Kingdom, the yellow card scheme--under which doctors report adverse drug reactions--has received 60 reports of serious cardiovascular reactions, five of which were fatal.

Worldwide there have been 386 reports of serious ventricular arrhythmias (125 of which were fatal) suspected to be due to cisapride and 50 reports of sudden unexplained death. Risk factors predisposing a patient taking cisapride to heart rhythm disturbances, such as interacting medicines, could be identified in many but not all cases.

In February the US Food and Drug Administration warned doctors that the drug should be used only as a last resort, for patients with the worst cases of gastro-oesophageal reflux disease when other treatments have failed (5 February, p 336). In July Janssen-Cilag suspended marketing of the drug in the United States, but cisapride is still available there through a limited access programme for patients who can show it is of "unique benefit."

Last week the Department of Health told patients to stop taking the drug and see their doctors over the next few weeks to discuss their treatment. "Stopping cisapride does not carry any risk," the advice said.

Concern about cardiac arrhythmias has recently led to a Europe-wide review of the risks and benefits of cisapride, which will consider what indications for the drug, if any, are justified. The suspension of UK licences will be reassessed once the review has been completed in 2001.

Professor Alasdair Breckenridge, chairman of the Committee on Safety of Medicines, said: "We have concluded that at the present time the balance of risks and benefits for cisapride is not favourable. There are several alternatives to cisapride available."

Health minister Lord Philip Hunt said: "The independent scientific advice of the Committee on Safety of Medicines means that measures short of suspending cisapride marketing authorisations are not adequate to protect UK public health, which is of course our priority."

Marketing of cisapride has also been suspended in Germany and Canada.

A spokesman for Janssen-Cilag UK said that serious cardiovascular adverse effects occurred principally in cases where the drug had been used "with contraindicated medicines or in patients with contraindicated comorbidities."

"Janssen-Cilag continues to believe that Prepulsid can be used with an acceptable benefit to risk ratio in appropriate patients."

COPYRIGHT 2000 British Medical Association
COPYRIGHT 2000 Gale Group