Interactions between ritonavir and Astemizole (astemizole)
astemizole and ritonavir (Major Drug-Drug)
CONTRAINDICATED: Coadministration with protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of astemizole and terfenadine. The mechanism is PI inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of both astemizole and terfenadine. Although the interaction has not been specifically studied with any of the available PIs, 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.
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 protease inhibitors is considered contraindicated. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with PIs.
