What antibiotics can cause prolonged QT interval?

From the Guidelines

Antibiotics such as macrolides, specifically azithromycin, erythromycin, and clarithromycin, as well as trimethoprim-sulfamethoxazole, can cause prolonged QT interval, increasing the risk of torsades de pointes and sudden cardiac death, particularly in patients with underlying risk factors such as female gender, advanced age, heart disease, or congenital long QT syndrome 1.

Key Points to Consider

• Macrolide antibiotics, including azithromycin, erythromycin, and clarithromycin, can directly prolong the QT interval and inhibit the metabolism of other proarrhythmogenic drugs, increasing the risk of malignant arrhythmias 1.
• Trimethoprim-sulfamethoxazole, particularly the sulfamethoxazole moiety, can also cause QT prolongation and torsades de pointes, especially in patients with genetic polymorphisms that affect potassium channel function 1.
• The risk of QT prolongation and torsades de pointes increases with higher doses, combination with other QT-prolonging medications, and in patients with risk factors such as electrolyte abnormalities, bradycardia, and heart disease 1.

Recommendations for Clinical Practice

• Clinicians should consider baseline ECG monitoring before starting these antibiotics in high-risk patients and avoid combinations of multiple QT-prolonging agents whenever possible.
• Regular monitoring of electrolytes and ECGs is recommended if these antibiotics must be used in at-risk patients.
• The use of alternative antibiotics with a lower risk of QT prolongation should be considered in patients with underlying risk factors.

From the FDA Drug Label

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 Moxifloxacin hydrochloride has been shown to prolong the QT interval of the electrocardiogram in some patients. Some fluoroquinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia.

The antibiotics that can cause prolonged QT interval are:

• Azithromycin 2
• Moxifloxacin 3
• Levofloxacin 4 These antibiotics may increase the risk of developing cardiac arrhythmia and torsades de pointes, especially in patients with known prolongation of the QT interval or other risk factors.

From the Research

Antibiotics that Cause Prolonged QT Interval

The following antibiotics have been associated with prolongation of the QT interval:

• Macrolides: erythromycin, clarithromycin, azithromycin 5, 6, 7
• Ketolides: telithromycin 5
• Fluoroquinolones: gatifloxacin, moxifloxacin, levofloxacin 5, 8
• Azole antifungals 8
• Pentamidine 8
• Antimalarials 8

Risk Factors for Prolonged QT Interval

The risk of prolonged QT interval is increased by:

• Concomitant use of other QT-prolonging drugs or agents that inhibit or are metabolized by CYP3A4 5, 6
• Electrolyte disturbances 5, 8
• Underlying cardiac disease 5, 6, 8
• Female sex 6
• Older age 6
• Severe illness 6

Comparison of Antibiotic Risks

The risk of QT interval prolongation varies among antibiotics, with:

• Erythromycin having the highest risk 5, 7
• Clarithromycin having a higher risk than azithromycin 7
• Gatifloxacin, moxifloxacin, and levofloxacin having a lower risk than erythromycin and clarithromycin 5
• Telithromycin's risk is yet to be determined 5