How can azithromycin cause bradycardia?

How Azithromycin Can Cause Bradycardia

Azithromycin can cause bradycardia primarily through its effects on cardiac ion channels, particularly by blocking the rapidly activating delayed rectifier potassium current (IKr) in cardiac cells, which can affect cardiac conduction and heart rate regulation. 1

Mechanisms of Azithromycin-Induced Bradycardia

Azithromycin affects the cardiovascular system through several mechanisms:

1. Direct effects on cardiac conduction:

   • Blocks potassium channels (IKr) in cardiac cells 1
   • Prolongs cardiac repolarization and QT interval 2
   • Can interfere with normal cardiac conduction tissue function 3

2. Indirect effects:

   • May inhibit the metabolism of other proarrhythmogenic drugs by acting on cytochrome P450 in the liver 3
   • Can exacerbate existing bradycardia or conduction disorders 3

Risk Factors for Azithromycin-Induced Bradycardia

Several factors increase the risk of developing bradycardia with azithromycin use:

• Pre-existing cardiac conditions:

  • History of heart disease 3
  • Pre-existing bradycardia 3
  • Prolonged QT interval before therapy 3
  • Uncompensated heart failure 2

• Demographic factors:

  • Advanced age (>80 years) 3
  • Female sex 3, 1

• Electrolyte abnormalities:

  • Hypokalemia 3, 1
  • Hypomagnesemia 3, 1

• Medication-related factors:

  • Concomitant use of other QT-prolonging medications 3, 1
  • Use of Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents 2

Clinical Presentation and Diagnosis

Bradycardia induced by azithromycin may present as:

• Symptomatic bradycardia (heart rate <60 beats per minute) 4
• Complete heart block in severe cases 5
• Associated QT prolongation 2
• Symptoms may include dizziness, fatigue, syncope, or in severe cases, cardiovascular collapse 4

The diagnosis is typically made by:

• Exclusion of other causes of bradycardia
• Temporal relationship between azithromycin administration and onset of bradycardia
• Resolution after discontinuation of the drug (though this may take several days due to azithromycin's long half-life) 6

Prevention and Management

To prevent azithromycin-induced bradycardia:

• Pre-treatment assessment:

  • Obtain baseline ECG prior to initiating therapy, especially in high-risk patients 1
  • Screen for history of heart disease, previous low serum potassium, slow pulse rate, family history of sudden death, or known prolonged QT interval 3
  • Review medication list for other QT-prolonging drugs 1
  • Check electrolyte levels (potassium and magnesium) 1

• During treatment:

  • Monitor ECG in high-risk patients 1
  • Perform follow-up ECG one month after initiating therapy 3
  • Maintain normal electrolyte levels 1

• If bradycardia occurs:

  • Discontinue azithromycin 2
  • Monitor cardiac rhythm 3
  • Maintain normal serum potassium 3
  • Consider temporary pacing in severe cases 3
  • Isoproterenol may be used to increase heart rate in emergency situations 3

Clinical Implications

The risk of serious cardiac events with azithromycin is relatively rare but potentially serious. The British Thoracic Society notes that fatal cardiac events occur in approximately 85 deaths per 1 million courses prescribed in high-risk groups 3. The risk of fatal ventricular arrhythmia with macrolides compared to amoxicillin is estimated at 1:4100 among high cardiovascular risk patients and <1:100,000 among low cardiovascular risk patients 1.

In pediatric patients, cases of moderate bradycardia have been reported, which may take many days to resolve due to the long tissue half-life of azithromycin 6.

For patients without additional risk factors, azithromycin appears to be relatively safe from a cardiac perspective, but clinicians should remain vigilant about the potential for bradycardia, especially in vulnerable populations 7.