Is azithromycin (Zithromax) safe to use in patients with Wolff-Parkinson-White (WPW) syndrome?

Safety of Azithromycin in Wolff-Parkinson-White Syndrome

Azithromycin should be used with caution in patients with Wolff-Parkinson-White syndrome due to its potential, albeit low, risk of QT prolongation which could theoretically precipitate arrhythmias in this vulnerable population. 1, 2

Risks Associated with Azithromycin in WPW

• Azithromycin carries a risk of QT interval prolongation and, rarely, torsades de pointes, though it has a lower risk profile compared to other macrolides such as erythromycin 1, 2
• The FDA label for azithromycin specifically warns about prolonged cardiac repolarization and QT interval, which can increase the risk of developing cardiac arrhythmias 2
• Patients with WPW syndrome are already at risk for dangerous arrhythmias, particularly if they develop atrial fibrillation, which can degenerate into ventricular fibrillation 3, 4

Risk Stratification for Azithromycin Use in WPW

• Higher risk WPW patients who should avoid azithromycin include:

  • Those with a history of symptomatic tachycardia 3
  • Patients with short RR intervals (<250 ms) during pre-excited atrial fibrillation 3
  • Patients with multiple accessory pathways 3, 5
  • Those with concomitant QT prolongation risk factors such as electrolyte abnormalities, congenital long QT syndrome, or use of other QT-prolonging medications 2

• Lower risk WPW patients where azithromycin might be considered with caution:

  • Asymptomatic patients with incidentally discovered WPW pattern 6
  • Patients who have undergone successful catheter ablation of their accessory pathway 3

Medication Considerations in WPW

• The primary concern in WPW is not direct QT prolongation but rather medications that might accelerate conduction through the accessory pathway during atrial fibrillation 5

• Medications absolutely contraindicated in WPW with pre-excited atrial fibrillation include:

  • Adenosine 5
  • Digoxin (oral or intravenous) 5
  • Nondihydropyridine calcium channel antagonists 5
  • Intravenous amiodarone 5

• While azithromycin is not specifically listed among these contraindicated medications, its QT-prolonging effects warrant caution 1, 2

Recommendations for Clinical Practice

• If antimicrobial therapy is necessary in a patient with WPW:

  • Obtain a baseline ECG before initiating azithromycin therapy 1
  • Consider alternative antibiotics without QT-prolonging effects if appropriate for the infection being treated 1, 2
  • If azithromycin must be used, monitor for QT prolongation and discontinue if QTc exceeds 500 ms 1
  • Maintain normal serum potassium and magnesium levels to reduce arrhythmia risk 1

• For patients with WPW who develop arrhythmias:

  • Immediate direct-current cardioversion is recommended for patients with pre-excited AF and hemodynamic compromise 5, 3
  • Intravenous procainamide or ibutilide can be used to restore sinus rhythm in hemodynamically stable patients with pre-excited AF 5, 3
  • Catheter ablation of the accessory pathway is the definitive treatment for symptomatic WPW syndrome 3, 6

Important Caveats

• The risk of sudden cardiac death in WPW is estimated at 0.15-0.2% annually in general WPW patients, but higher (2.2%) in symptomatic patients 3
• Approximately 25% of patients with WPW syndrome have accessory pathways with short anterograde refractory periods (<250 ms), which increases the risk of rapid ventricular rates and ventricular fibrillation 5
• Atrial fibrillation occurs in up to 50% of patients with WPW syndrome, making medication choices particularly important 4
• Even after successful ablation, some patients may still develop atrial fibrillation, requiring continued caution with QT-prolonging medications 5, 3