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Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice

[ Vol. 11 , Issue. 1 ]

Author(s):

Guillermo A. Keller, Paulino A. Alvarez, Marcelo L. Ponte, Waldo H. Belloso, Claudia Bagnes, Cecilia Sparanochia, Claudio D. Gonzalez, M. Cecilia Villa Etchegoyen, Roberto A. Diez and Guillermo Di Girolamo   Pages 86 - 98 ( 13 )

Abstract:


Objective: The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed.

Research Design and Methods: Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula.

Results: Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis.

Conclusion: QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Keywords:

Adverse drug reaction, QT-Interval prolongation, torsade des Pointes, arrhythmia.

Affiliation:

University of Buenos Aires, Argentina.



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