Does the co-administration of terfenadine and ketoconazole cause torsades de pointes?
This case report provides the first evidence of torsades de pointes associated with recommended doses of terfenadine when co-administered with ketoconazole, likely due to metabolic inhibition.
Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose.
Brian P. Monahan (Wed,) studied this question.
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