Interactions between tagamet(cimetidine) and Cisapride (cisapride)
cimetidine and cisapride (Major Drug-Drug)
GENERALLY AVOID: Coadministration with cimetidine may increase the plasma concentrations of cisapride. The mechanism is cimetidine inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of cisapride. In eight healthy volunteers, cimetidine (400 mg orally three times a day) increased the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cisapride (10 mg orally three times a day) by 45% each. No adverse effects have been attributed to this interaction, although 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. Conversely, cisapride may accelerate but decrease the extent of gastrointestinal absorption of cimetidine. In the eight volunteers, the time to reach peak concentration (Tmax) of cimetidine reduced by about one-half during coadministration with cisapride, and the bioavailability decreased by 18%.
MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of cisapride, concurrent use of cimetidine should be avoided if possible. Other H2-receptor antagonists (e.g., famotidine, nizatidine, ranitidine) have not been shown to significantly inhibit CYP450 3A4 and may be safer alternatives during therapy with cisapride.
