title: Erythromycin, QTc interval prolongation, and torsade de pointes: Case reports, major risk factors and illness severity.
abstract: OBJECTIVE
  Erythromycin is a macrolide antibiotic that is widely used for various infections of the upper respiratory tract, skin, and soft tissue. Similar to other macrolides (clarithromycin, azithromycin), erythromycin has been linked to QTc interval prolongation and torsade de pointes (TdP) arrhythmia. We sought to identify factors that link to erythromycin-induced/associated QTc interval prolongation and TdP.
  
  
  RESULTS
  In a critical evaluation of case reports, we found 29 cases: 22 women and 7 men (age range 18-95 years). With both oral and intravenous erythromycin administration, there was no significant relationship between dose and QTc interval duration in these cases. Notably, all patients had severe illness. Other risk factors included female sex, older age, presence of heart disease, concomitant administration of either other QTc prolonging drugs or agents that were substrates for or inhibitors of CYP3A4. Most patients had at least two risk factors.
  
  
  CONCLUSIONS
  On the basis of case report evaluation, we believe that major risk factors for erythromycin-associated TdP are female sex, heart disease and old age, particularly against a background of severe illness. Coadministration of erythromycin with other drugs that inhibit or are metabolized by CYP3A4 or with QTc prolonging drugs should be avoided in this setting.
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.affiliation: Department of Psychiatry, Memorial University, St John's, Newfoundland, Canada.
authors.forename: Mehrul
authors.initials: M
authors.lastname: Hasnain
authors.affiliation: Departments of Psychiatry and Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: W Victor R
authors.initials: WV
authors.lastname: Vieweg
authors.affiliation: School of Medicine, Department of Cardiology, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Gysel
authors.affiliation: Department of Pharmacy, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Methot
authors.affiliation: School of Medicine, Department of Cardiology, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Baranchuk
keywords: drug-induced QTc interval prolongation; erythromycin; risk factors; torsade de pointes