Interactions between ketoconazole and Astemizole (astemizole)
ketoconazole and astemizole (Major Drug-Drug)
CONTRAINDICATED: Coadministration with azole antifungal agents may significantly increase the plasma concentrations of astemizole. The mechanism is azole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of astemizole. High plasma levels of astemizole have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia 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.
MANAGEMENT: The use of astemizole with most azole antifungal agents is considered contraindicated. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with azole antifungal agents.
