Cisapride arrhythmia with

Cisapride has comparable efficacy to H2RAs in patients with mild esophagitis. It is no longer available for routine use because of life-threatening arrhythmias when combined with certain medications and other disease states. It is currently available only through a limited access program from the manufacturer. 

Do not administer concurrently with cisapride, midazolam, triazolam, or ergot derivatives. Competition for CYP3A4 by efavirenz could result in inhibition of metabolism of these drugs and create the potential for serious or life-threatening adverse events (eg, cardiac arrhythmias, prolonged sedation, respiratory depression see Drug Interactions). 

Nausea Usually transient and dose-related. May improve with dose reduction or symptomatic measures (e.g., food, antacids, addition of drugs that block 5-HT 3 receptors, such as cisapride). There has been increasing concern about using cisapride in combination with antidepressants that can substantially inhibit CYP 3A3/4 (i.e., fluvoxamine, nefazodone). The reason is that high levels of cisapride can cause arrhythmias as a result of delayed intracardiac conduction. 

Concomitant administration of clarithromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated. There have been postmarketing reports of drug interactions when clarithromycin and/ or erythromycin are coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes). 

Due to prokinetic effects in the colon, abdominal cramps and diarrhea occur in up to 15% of patients taking cisapride however significant problems are unusual. In addition, cisapride is metabolized by the hepatic cytochrome P450 CYP3 A4 enzyme. When coadministered with drugs that inhibit this enzyme (such as ketoconazole, fluconazole, macrolide antibiotics, and HIV protease inhibitors), significant increases in serum levels of cisapride may occur that rarely lead to QT prolongation on the ECG and serious cardiac arrhythmias. For this reason, cisapride was removed... 

Torsades de pointes, a life-threatening ventricular arrhythmia associated with QT prolongation, can occur when these inhibitors are coadministered with terfena-dine, astemizole, or cisapride because they inhibit these agents from converting the parent compound into nontoxic, pharmacologically active metabolites. 

Chan-Tompkins, N.H. Babinchak, T.J. Cardiac arrhythmias associated with coadministration of azole compounds and cisapride. Clin. Infect. Dis. 1997, 24 (6), 1285-1313. 

In the past decade there has been increased emphasis on drug safety, and more public visibility of safety problems. The volume of reports now exceeds 250 000 spontaneous reports per year, and adverse events have been highlighted in the medical sector and also in the media. In parallel, the FDA has focused more intently on this area in both NDA reviews and in the postmarketing period. This has accompanied withdrawals of a number of products, such as cisapride, phenylpropanolamine and terfenadine, and special scrutiny of products associated with particular adverse events, such as cardiac arrhythmias (torsades de Pointes ) and hepatic necrosis. The result has been an emphasis on the concept of risk management of a product. This concept, which is due to be described in forthcoming FDA recommendations, stresses the need to identify potential... 

Telithromycin may cause clinically significant QTc prolongation and increased risk of ventricular arrhythmia in predisposed patients. It should not be used in patients with prolonged QT syndrome, uncorrected hypokalemia or hypomagnesemia, profound bradycardia, or in patients receiving certain antiarrhythmics (e.g., quinidine, procainamide, amiodarone) or other agents that prolong QTc (e.g., cisapride, pimozide). 

Absolute aprepitant is contraindicated in patients who are hypersensitive to any component of the product. Aprepitant is a weak-to-moderate (dose-dependent) cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Aprepitant should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Dose-dependent inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening ventricular arrhythmias. 

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