TERFENADINE, KETOCONAZOLE, AND CARDIAC ARRHYTHMIAS.

The nonsedating antihistamine terfenadine has been linked to torsades de pointes, a cardiac arrhythmia, particularly when prescribed with ketoconazole. Two studies evaluated this potential drug interaction.

In the first, investigators gave oral terfenadine (60 mg twice daily) to six healthy volunteers for 7 days. They then added oral ketoconazole (200 mg twice daily) to the regimen. After the addition of the antifungal agent, all six subjects had detectable plasma levels of unmetabolized terfenadine and prolongation of the QT interval on electrocardiograms. Four of the six subjects had ketoconazole discontinued after less than 1 week because of ECG changes.

An in vitro study evaluated the electrophysiologic properties of terfenadine and its m…