Interactions between diflucan(fluconazole) and Propulsid (cisapride)
fluconazole and cisapride (Major Drug-Drug)
CONTRAINDICATED: Coadministration with azole antifungal agents may significantly increase the plasma concentrations of cisapride. The mechanism is azole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of cisapride. High plasma levels of cisapride have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death. Within the azole class, ketoconazole and itraconazole are considered the most potent inhibitors, while fluconazole is comparatively weak and generally causes clinically significant interactions with CYP450 3A4 substrates only at dosages of 200 mg/day or more. In humans, coadministration with oral ketoconazole has resulted in a mean eight-fold increase in the area under the plasma concentration-time curve (AUC) of cisapride. Fluconazole 200 mg daily for 7 days increased the peak plasma concentration (Cmax) and AUC of cisapride following multiple dosing (20 mg four times a day) by 153% and 192%, respectively. Prolongation of the QT interval have been reported with both combinations in clinical studies.
MANAGEMENT: The use of cisapride with most azole antifungal agents is considered contraindicated.
