Janssen Propulsid concomitant use with Nizoral contraindicated due to association with arrhythmias.

JANSSEN PROPULSID CONCOMITANT USE WITH NIZORAL CONTRAINDICATED because of the potential for prolonged QT interval and rare association with ventricular arrhythmia and torsades de pointes, new warnings in Propulsid's labeling state. Janssen Pharmaceutica informed pharmacists and physicians of the new safety information about the nocturnal heartburn treatment in letters sent out in early February.

"Concomitant administration of Propulsid (cisapride) with ketoconazole [Nizoral] tablets is contraindicated because it resulted in markedly elevated cisapride plasma concentrations and prolonged QT interval, and rarely has been associated with ventricular arrhythmia and torsades de pointes," new labeling language states. The "Dear Pharmacist" and "Dear Doctor" letters contain the revised prescribing information.

The warnings section of labeling notes that "some of these patients did not have known cardiac histories; however, most had been receiving multiple other medications and had pre-existing cardiac disease or risk factors for arrhythmias."

"Through the spontaneous [adverse event] reporting system in the U.S., the reporting rate of serious ventricular arrhythmias in patients treated with Propulsid has been approximately one per 120,000 patients and approximately one per 400,000 patient-months," the "Dear Pharmacist" letter states.

"Two of the reports of ventricular arrhythmias, including torsades de pointes associated with QT prolongation, occurred in patients taking Propulsid tablets and Nizoral. Plasma concentration measurements suggested a possible interaction."

Explaining the interaction, Janssen pointed out in the letter that "oral ketoconazole potently inhibits the cytochrome P450 enzyme system (3A4) mainly responsible for cisapride metabolism."

For this reason, Janssen's antifungals Sporanox (itraconazole) capsules and Monistat (miconazole) I.V., and Roerig's antibiotic TAO (troleandomycin) capsules, "are also expected to markedly raise cisapride plasma concentrations," the warnings say. "Therefore, concomitant use of Propulsid with these three products is also contraindicated." Janssen added that the labeling for the antifungals and the antibiotic also will be revised.

Similarly, the labeling for Janssen's antihistamine Hismanal and Marion Merrell Dow's antihistamine Seldane was revised in July 1992 when it was discovered that administration of Seldane or Hismanal with ketoconazole, itraconazole, erythromycin or other antibiotics resulted in rare cases of serious cardiac events, including torsades de pointes and ventricular arrhythmias.