Chairman, Department of Medicine, Danbury Hospital, Danbury, CT 06810, and Clinical Professor of Medicine, Yale University School of Medicine, New Haven, CT, USA
Sir,
James Kahn's recent correspondence on the issue of QTc prolongation as a class effect of the fluoroquinolones adds insight into the cellular effects of these drugs on cardiac repolarization.1 His arguments are heavily weighted by animal data with no reference to human studies of levofloxacin and its effects on QTc intervals. We recently reported an association between levofloxacin and torsades de pointes (TdP) in a patient taking amiodarone concurrently (a type III antiarrhythmic agent), as well as a median QTc prolongation of 4.6 ms for 37 patients on levofloxacin alone.2 Of these patients, 14% met CPMC criteria3 for raises clear concerns. We have since encountered a second case occurring in a patient on these same two agents and both have been reported to the United States Food and Drug Administration (FDA) and the R. W. Johnson Pharmaceuticals Research Institute: Ortho-McNeil Pharmaceuticals. A similar case has been reported by Samaha.4 While animal data are helpful and binding affinities of fluoroquinolones to cardiac cellular repolarization channels is of great scientific interest, only human studies are definitive in terms of toxicity. Levofloxacin does prolong the QTc interval and with amiodarone produces the potential for TdP. Spontaneous reporting of adverse events is not a completely reliable index of drug toxicity and should be interpreted as a signal for more extensive human studies. I would urge caution in the use of levofloxacin and all other fluoroquinolones and macrolides with type IA and type III antiarrhythmic agents in patients with other risk factors for TdP, despite the manufacturers' package inserts.
Notes
J Antimicrob Chemother 2001; 47: 893894
* Tel: +1-203-797-7985; Fax: +1-203-830-2047; E-mail: paul.iannini{at}danhosp.org
References
1
.
Kahn, J. (2000). Quinolone-induced QT interval prolongation: a not-so-unexpected class effect. Journal of Antimicrobial Chemotherapy 46, 8478.
2 . Iannini, P., Doddamani, S., Byazrova, E., Circiumaru, J. & Kramer, H. (2000). QTc prolongation associated with levofloxacin. In Program and Abstracts of the Fortieth Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 2000. Abstract 822, p. 477. American Society for Microbiology, Washington DC.
3 . Proprietary Medicinal Products, The European Agency for the Evaluation of Medicinal Products. Points to consider: the assessment of the potential for QT interval prolongation by noncardiovascular medicinal products. 17 December 1997. [On-line.] http://WWW.eudra.org/humandocs/PDFs?SWP/09869en.pdf
4 . Samaha, F. F. (1999). QTc interval prolongation and polymorphic ventricular tachycardia associated with levofloxacin. American Journal of Medicine 107, 5289.[ISI][Medline]