Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes

• Published in: The New England journal of medicine Vol. 351; no. 11; pp. 1089 - 1096
• Main Authors: Ray, Wayne A, Murray, Katherine T, Meredith, Sarah, Narasimhulu, Sukumar Suguna, Hall, Kathi, Stein, C. Michael
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 09.09.2004
• Subjects: Administration, Oral; Adult; Aged; Amoxicillin - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - metabolism; Biological and medical sciences; Calcium Channel Blockers - adverse effects; Confounding Factors (Epidemiology); Cytochrome P-450 CYP3A; Death, Sudden, Cardiac - etiology; Diltiazem - adverse effects; Drug Interactions; Drug therapy; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Erythromycin - adverse effects; Erythromycin - therapeutic use; Female; General aspects; Humans; Intensive care medicine; Male; Medicaid; Medical research; Medical sciences; Middle Aged; Multivariate Analysis; Nitroimidazoles - adverse effects; Oxidoreductases, N-Demethylating - antagonists & inhibitors; Oxidoreductases, N-Demethylating - metabolism; Risk; Studies; Troleandomycin - adverse effects; Verapamil - adverse effects; USA, Tennessee; Medicine; Antibiotic; Sudden death; Cause; Risk factor; Oral administration; Risk; Erythromycin; Antibacterial agent; Macrolide
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa040582

Erythromycin is known to prolong cardiac repolarization and has been associated with case reports of torsades de pointes. In this study, the use of oral erythromycin was found to increase the risk of sudden death from cardiac causes by a factor of two. The concurrent use of erythromycin and cytochrome P-450 inhibitors, such as verapamil or diltiazem, increased the risk by a factor of five. Thus, erythromycin should not be prescribed for patients receiving these drugs. The concurrent use of erythromycin and cytochrome P450 inhibitors increased the risk by a factor of five. Erythromycin is a commonly used macrolide antimicrobial agent with a long history of use, and it is considered largely free of serious toxicity. However, there have been case reports of torsades de pointes in patients receiving both oral and intravenous erythromycin. 1 – 4 An increase in the risk of torsades de pointes is consistent with the effects of erythromycin on cardiac electrophysiology; studies have shown prolongation of the QT interval 5 , 6 and blockade of the potassium channel encoded by the human ether-a-go-go–related gene ( HERG ). 7 There are important clinical questions that these case reports have not addressed. Although there is . . .