ITRACONAZOLE PREVENTS TERFENADINE METABOLISM AND INCREASES RISK OF TORSADES-DE-POINTES VENTRICULAR-TACHYCARDIA

Terfenadine, a nonsedating H-1-selective antihistamine, is widely used in many countries. We report pharmacokinetic results in a patient who developed a prolonged QT-interval in ECG and symptomatic torsades de pointes ventricular tachycardia as a consequence of the interaction of itraconazole and terfenadine. Both drugs were taken in the recommende d doses: terfenadine 60 mg b. d. and itraconazole 100 mg b. d. Terfena dine metabolism was delayed by itraconazole, leading to an increased l evel of unmetabolised terfenadine. Seven weeks after the cessation of itraconazole treatment, terfenadine was rapidly metabolized to its act ive metabolite and did not prolong the QT-interval when given as a sin gle provocation dose (120 mg). The findings suggest that intraconazole in therapeutic doses inhibits terfenadine metabolism. It is also poss ible that unmetabolised terfenadine alone, without an increased level of its active metabolite, may cause torsades de pointes. The concomita nt use of terfenadine and itraconazole (and ketoconazole) should be av oided.