Skipping a Beat

A KEY ADVERSE DRUG REACTION

In the autumn of 1989, a previously healthy 39-year-old woman was transferred to Bethesda Naval Medical Center after having experienced several episodes of palpitations and near syncope. Her presenting electrocardiogram was very abnormal, displaying a prolonged QT interval with inverted T waves and prominent U waves. Because of the nature of her symptoms and her abnormal ECG, she was placed on a cardiac monitor. In the hours that followed she experienced two more episodes of palpitations, which correlated on telemetry with runs of polymorphic ventricular tachycardia. The occurrence of polymorphic ventricular tachycardia in the setting of a prolonged QT interval fulfilled the definition of torsades de pointes, a syndrome first described in 1966 by the French cardiologist, Dessertenne, most often in association with the use of antiarrhythmic drugs.

Two weeks prior to hospitalisation, the patient had visited her primary care physician complaining of seasonal allergies and sinusitis. She had been given prescriptions for a broad-spectrum antibiotic and for the non-sedating antihistamine terfenadine. After one week of concomitant therapy she felt better but developed Candida vaginitis, a complication of her antibiotic therapy. She was instructed to discontinue her antibiotic, to treat her yeast infection topically and to continue taking terfenadine.

Because her gynaecological symptoms were not improving rapidly enough, she self-medicated with ketOconazole tablets that she found in her medicine cabinet. It is only after 48 hours of concomitant terfenadine and ketOconazole therapy that she developed her cardiac symptoms. Upon admission to the hospital, all her medications were stopped, she had no further episodes of polymorphic ventricular tachycardia and her QT interval normalised.