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Letters to the Editor Indian Pediatrics 2000;37: 1402-1404 |
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Use of Cisapride |
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The safety of the use of cisapride has been under cloud for some time with reported incidences of cardiac arrhythmias and of deaths caused by it. One study showed that 11 of 35 children (31%) receiving cisapride had prolonged QTc (>450 ms), and 2 had docu-mented torsades de pointes ventricular tachycardia(3). As of December 1999, use of cisapride had been associated with 341 reports of heart rhythm abnormalities, in-cluding 80 reports of deaths, according to the U.S. Food and Drug Administration(4). This proarrhythmia may be exacerbated by other medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. Many commonly used anti- allergy drugs, anti-angina drugs, antibiotics, anti-depressants, anti-fungals, anti-nauseants and anti-psychotics can exacerbate this arrhythmia. Conversely, there are probably several studies showing its effectiveness in gastro-esophageal reflux disease (GERD) and constipation, with many showing its safety also, specifically with regards to its cardiac effects. But the evidence in support of its potential to cause cardiac arrhythmias has become strong enough to make its apparent usefulness of doubtful value and not sufficient to justify its use in conditions where other safer alternatives are available. Since the drug’s approval in 1993, Cisapride’s labeling has been revised several times, most recently in January 2000, to inform health care professionals and patients about the drug’s risks. Despite these efforts, Janssen Pharmaceutics Inc. of U.S.A. decided in consultation with the FDA that continued general use in U.S.A. poses unacceptable risks(4). As a result, cisapride marketing has been stopped in the U.S.A. from July 4, 2000, by its manufacturer Janssen Pharmaceutics Inc.(4). Such reporting of the side effects of drugs and prompt action to curtail its use is rather slow if not nil in India. This note is to inform the readers of this journal of the recent change in the status of the use of cisapride in U.S.A. As always, the dictum "primum non necere" may be all the more apt here, as there are many other safer drugs for use in conditions where cisapride is now being used. Alexander Mathew,
We agree with Dr. Mathew that one may switch over to alternate drug other than cisapride in the setting of feed intolerance and gastroesophageal reflux disease in neonates, in view of current evidence regarding lack of safety and efficacy of cisapride(1,2). Our study was designed at a time when there were no published randomized controlled trials using cisapride prophylactically to improve feed tolerance in preterm neonates. At that time not much published data was there on safety of cisapride in neonates. The primary objective of our study was to evaluate the efficacy of cisapride on gastric emptying time, in view of rampant (unofficial) use of cisapride without much evidence in preterm neonates. Now along with ours, other randomized studies have shown the doubtful efficacy of cisapride(3,4,5). The present evi-dence suggests a higher incidence of compli-cations in infants and children receiving cisapride specially at higher dosage and with concomitant use of other drugs (macrolide antibiotics and azole antifungals(6-8). Premature infants treated with cisapride are thought to be specifically at risk of QTc prolongation. Hence, it is recommended that all premature infants (£36 weeks of gestation) going to be started on cisapride should have a baseline ECG which is repeated three days later(8). A.K. Deorari,
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