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Brian P. Monahan, MD; Clifford L. Ferguson, MD; Eugene S. Killeavy, MD; Bruce K. Lloyd, MD; James Troy; Louis R. Cantilena, Jr, MD, PhD

JAMA. 1990;264(21):2788-2790.

Abstract
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.

(JAMA. 1990;264:2788-2790)

Author Affiliations
From the Divisions of Internal Medicine (Dr Monahan) and Cardiology (Drs Killeavy and Lloyd), Department of Medicine, National Naval Medical Center, and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology (Drs Cantilena and Ferguson and Mr Troy), Uniformed Services University of the Health Sciences, Bethesda, Md.

Footnotes
The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Navy, the Uniformed Services University of the Health Sciences, the Department of Defense, or the US government.

Reprint requests to Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814-4799 (Dr Cantilena).

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