Cardiac actions of erythromycin: influence of female sex.
BACKGROUND
Erythromycin is a widely used antibiotic that infrequently causes QT-prolongation and torsades de pointes cardiac arrhythmias. For antiarrhythmic drugs, women are at a higher risk for these cardiac arrhythmias, but few other classes of drugs have been studied.


OBJECTIVE
To determine whether female sex is a risk factor for cardiac arrhythmias associated with erythromycin, and if this can be correlated with in vitro measurements of the QT-response to erythromycin in male and female rabbit hearts.


METHODS
Food and Drug Administration (FDA) MEDWATCH database analysis and in vitro experiment.


METHODS
Cardiac 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 hearts.


RESULTS
We observed a sex difference in cardiac arrhythmias associated with administration of erythromycin. A total of 346 cases were found in the FDA database: 201 females (58%), 110 males (32%), and 35 unspecified (10%). Forty-nine were life-threatening ventricular arrhythmias and deaths directly related to intravenous erythromycin lactobionate: 33 women (67%) and 16 men (33%) (P=.03). During the same period, no sex imbalance was present in the prescription pattern for intravenous erythromycin lacobionate (men 47%, women 49%, unspecified 4%). Perfusion 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 antiarrhythmic drugs, we found a female predominance in the FDA reports of erythromycin-associated cardiac arrhythmias. Based on in vitro experiments, a sex difference in cardiac repolarization response to erythromycin is a potential contributing factor.
Drici
M D
MD
Georgetown University Medical Center, Washington, DC 20007, USA.
Knollmann
B C
BC
Wang
W X
WX
Woosley
R L
RL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D004594:Electrophysiology; D004917:Erythromycin / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D012307:Risk Factors; D012737:Sex Factors
D000900:Anti-Bacterial Agents; D004917:Erythromycin