CARDIAC ACTIONS OF ERYTHROMYCIN - INFLUENCE OF FEMALE SEX

Context.-Erythromycin is a widely used antibiotic that infrequently ca uses QT-prolongation and torsades de pointes cardiac arrhythmias. For antiarrhythmic drugs, women are at a higher risk for these cardiac arr hythmias, but few other classes of drugs have been studied. Objectives .-To determine whether female sex is a risk factor for cardiac arrhyth mias associated with erythromycin, and if this can be correlated with in vitro measurements of the QT-response to erythromycin in male and f emale rabbit hearts. Design.-Food and Drug Administration (FDA) MEDWAT CH database analysis and in vitro experiment. Main Outcome Measures.-C ardiac arrhythmia reports associated with erythromycin from 1970 until 1996 classified by patient sex and age, and effect: of female sex on erythromycin-induced QT-prolongation in isolated perfused rabbit heart s. Results.-We observed a sex difference in cardiac arrhythmias associ ated with administration of erythromycin. A total of 346 cases were fo und in the FDA database: 201 females (58%), 110 males (32%), and 35 un specified (10%). Forty-nine were life-threatening ventricular arrhythm ias and deaths directly related to intravenous erythromycin lactobiona te: 33 women (67%) and 16 men (33%) (P = .03). During the same period, no sex imbalance was present in the prescription pattern for intraven ous erythromycin lacobionate (men 47%, women 49%, unspecified 4%). Per fusion with erythromycin caused significantly greater QT-prolongation in female rabbit hearts (mean [SD], 11.8% [2.3%]) than in male hearts (6.9% [2.1%]; P = .03). Conclusions.-As has been shown in reports of a ntiarrhythmic drugs, we found a female predominance in the FDA reports of erythromycin-associated cardiac arrhythmias. Based on in vitro exp eriments, a sex difference in cardiac repolarization response to eryth romycin isa potential contributing factor.