QT Interval Prolongation Associated with High-Dose Azithromycin Therapy: A Clinical Pharmacology-Ba
DOI:
https://doi.org/10.64149//J.Ver.8.20s.281-290Keywords:
Azithromycin; QTc interval; QT prolongation; macrolide antibiotics; cardiac safety; torsades de pointes; high-dose therapy; pharmacokinetics; ECG monitoring; arrhythmia risk.Abstract
Background: Azithromycin is a widely used macrolide antibiotic with a favorable safety profile; however, emerging data suggest it may induce QT interval prolongation, particularly at high doses and in vulnerable populations. This study evaluates the electrophysiological effects of high-dose azithromycin therapy and explores clinical and pharmacokinetic predictors of QTc prolongation.
Methods: A multicenter, prospective, observational study was done in 180 hospitalized adults taking azithromycin 1 g/day, on infectious indications. ECGs were recorded in ser12-leads to determine the change in QTc on the basis of Bazett and Fridericia corrections. Lab data, comorbidity and co-administered medications were recorded. Exposure-response model pharmacokinetic sampling was conducted on 60 patients. Statistical analysis was done in form of paired t-tests, logistic regression and correlation.
Results: The mean QTc rose dramatically in the course of the therapy (Bazett: 423.6 +- 21.4 ms to 448.2 +- 29.1 ms, p < 0.001). QTc [?]500 ms was found in 6.7% of patients and 11.7% of them had DQTc [?]60 ms. Women, hypokalemia, and chronic kidney disease and concomitant QT-prolonging medications were all important predictors of QTc [?]500 ms. Pharmacokinetic analysis found a small relationship between the plasma azithromycin concentrations and the QTc change (r = 0.28, p = 0.046).
Conclusion: High-dose azithromycin is associated with dose- and risk-dependent QTc prolongation, often reversible and manageable with appropriate monitoring. Clinical vigilance, including baseline ECGs and electrolyte correction, is essential to mitigate arrhythmic risk, particularly in high-risk patients.
