Do ceftriaxone (Ceftriaxone) or azithromycin (Azithromycin) affect the QTc (QTc interval)?

From the Guidelines

Azithromycin can prolong the QTc interval, while ceftriaxone generally does not have significant QTc-prolonging effects. Azithromycin, a macrolide antibiotic, carries a moderate risk of QTc prolongation, particularly in patients with pre-existing cardiac conditions, electrolyte abnormalities (especially hypokalemia or hypomagnesemia), or in those taking other QTc-prolonging medications, as noted in a study published in the Journal of the American College of Cardiology 1. The risk appears to be dose-dependent and may be higher with intravenous administration.

When prescribing azithromycin to patients with risk factors for QTc prolongation, consider obtaining a baseline ECG and monitoring during treatment. Ceftriaxone, a third-generation cephalosporin, is not significantly associated with QTc prolongation in clinical practice and is generally considered safe from a cardiac perspective. If treating a patient with multiple risk factors for QTc prolongation who requires antibiotic therapy, ceftriaxone would be the safer choice between these two medications when clinically appropriate for the infection being treated.

The mechanism for azithromycin's QTc effect involves blocking of potassium channels in cardiac cells, which delays cardiac repolarization and extends the QTc interval. Although an older study published in Circulation in 2009 also discussed the potential for macrolides, including azithromycin, to cause QT interval prolongation 1, the more recent and higher-quality evidence from the Journal of the American College of Cardiology 1 supports the recommendation to prioritize ceftriaxone over azithromycin in patients at risk for QTc prolongation. Key considerations include:

• Patient risk factors for QTc prolongation
• The dose-dependent nature of azithromycin's effect on the QTc interval
• The importance of baseline and monitoring ECGs in at-risk patients
• The safer cardiac profile of ceftriaxone compared to azithromycin in this context.

From the FDA Drug Label

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with azithromycin (500 mg, 1000 mg, and 1500 mg once daily) Co-administration of azithromycin increased the QTc interval in a dose-and concentration-dependent manner. Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including azithromycin

Azithromycin affects the QTc interval.

• The FDA drug label for Azithromycin reports that co-administration of azithromycin increased the QTc interval in a dose-and concentration-dependent manner.
• Prolonged cardiac repolarization and QT interval have been seen in treatment with macrolides, including azithromycin. There is no information about Ceftriaxone in the provided drug labels that directly supports an answer to the question. 2, 2

From the Research

Effect of Ceftriaxone and Azithromycin on QTc Interval

• Ceftriaxone's effect on the QTc interval is not directly addressed in the provided studies, but its combination with azithromycin is mentioned in some studies without specific reference to its individual impact on QTc prolongation.
• Azithromycin's impact on the QTc interval has been studied extensively:
  • A study from 2015 3 found that azithromycin was not associated with QT prolongation in patients with community-acquired pneumonia.
  • A 2024 study 4 concluded that azithromycin use was not associated with a statistically significant increase in QTc interval, suggesting that for the majority of patients, QTc prolongation is not a major concern.
  • However, a 2017 study 5 observed a significant increase in QTc in patients treated with azithromycin and cetirizine for upper respiratory tract infections, indicating a potential risk for QTc prolongation, especially in patients with a baseline QTc greater than 377.5 ms.
  • A 2018 study 6 found that the risk of QT prolongation was increased when patients, particularly the elderly, were exposed to azithromycin, with an odds ratio of 1.40 for QT prolongation.
  • A 2021 study 7 showed that QTc interval prolongation was associated with inpatient azithromycin therapy for pneumonia, with a significant increase in QTc interval after one dose of azithromycin.

Key Findings

• The evidence regarding azithromycin's effect on the QTc interval is mixed, with some studies finding no significant association and others indicating a potential risk, particularly in certain patient populations.
• Ceftriaxone's individual effect on the QTc interval is not well-represented in the provided studies.
• Clinicians should exercise caution when prescribing azithromycin, especially to patients at high risk for QTc prolongation, such as the elderly or those with pre-existing cardiovascular conditions 6.