Cisapride

A pediatric protocol will be included in a limited-access program for cisapride; the program will soon be the only way to obtain the drug for patients, said a spokesperson for Janssen Pharmaceutica Inc.

Janssen will stop marketing cisapride tablets and suspension on July 14 in response to continued reports of cardiac arrhythmias, including fatal arrhythmias, among people taking the drug. Cisapride, marketed under the brand name Propulsid, is approved for the treatment of nocturnal heartburn caused by gastroesophageal reflux disease (GERD) in adults. However, it is widely used off label in infants and children with severe GERD or other conditions.

As of December 31, 1999, 341 cases of heart rhythm abnormalities had been reported in people on cisapride, including 44 cases in children under 19 years of age, according to a Food and Drug Administration spokesperson. There were 80 fatal cases, including 14 fatal cases among children aged 27 days to 18 years.

Of the 44 pediatric cases, 23 cases occurred in children aged 1 year or younger, 6 cases in children aged 13 months through 2 years, 5 cases in children aged 3 through 9 years, and 10 cases in children aged 10 through 18 years.

The majority of the arrhythmias occurred in those who had underlying conditions or those taking other medications known to increase the risk of arrhythmias in combination with cisapride, according to a statement by the FDA. These risk factors are included in cisapride's labeling, which has been revised several times since the drug was approved in 1993.

Despite these risk management efforts, which have induded several "Dear Doctor" letters, Janssen in consultation with the FDA has decided that "continued general U.S. prescription access to the drug poses unacceptable risks," according to the FDA.

After July 14, physicians will be able to prescribe cisapride under a limited-access program. The drug "will remain available to appropriate patients for whom other therapies are not effective and which meet clearly defined eligibility criteria," said a statement fromJanssen. Neither the FDA's statement nor Janssen's statement mentions pediatric use.

Greg Panico, a spokesperson for Janssen, told PEDIATRIC NEWS that the limited-access program will include a protocol for pediatric use, but he was not able to provide any details.

Pediatric gastroenterologist Robert J. Shulman is annoyed with the decision to stop marketing cisapride "because it's another example of politics and the threat of litigation overriding science." There is no alternative to cisapride for newborns and older children with motility disorders who have responded to cisapride, he said.

The decision also has made the parents of children on the drug extremely fearful, he added. But as far as he knows, all the cases of arrhythmias and fatalities in children have been in patients with contraindications. "It is clearly a drug that has some risks," but the risk is far less than the risks of other drugs, he said, citing the risk of a severe reaction to penicillin as much greater.

Dr. Shulman lauded the company's decision to include a pediatric protocol, although he said it may still be difficult for patients who need the drug to obtain it. He is the chair of a committee of the North American Society for Pediatric Gastroenterology and Nutrition that responded to a warning about the potential for cardiac arrhythmia with cisapride. In a paper published in May 1999, the group said that adverse effects could be reduced by carefully selecting patients, avoiding contraindicated drugs, and counseling.

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COPYRIGHT 2001 Gale Group