Interactions between vaprisol(conivaptan) and Astemizole (astemizole)
astemizole and conivaptan (Major Drug-Drug)
GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of astemizole and terfenadine. The mechanism is conivaptan inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these antihistamines. Although the interaction has not been specifically studied, high plasma levels of astemizole and terfenadine (e.g., due to overdose or interaction with other potent 3A4 inhibitors such as macrolide antibiotics and azole antifungal agents) 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. In pharmacokinetic studies with other drugs that are primarily metabolized by CYP450 3A4 such as midazolam, simvastatin, and amlodipine, conivaptan has increased systemic exposure (AUC) by 2- to 3-fold.
MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of astemizole and terfenadine, use of these agents in patients treated with conivaptan should be avoided. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with conivaptan.
