Is clarithromycin (Biaxin) use in pneumonia associated with an increased risk of cardiovascular death?

Clarithromycin Use in Pneumonia and Cardiovascular Death Risk

Clarithromycin use in pneumonia is associated with a small short-term risk of cardiovascular events, but evidence for long-term increased cardiovascular mortality is inconsistent and not clearly established in patients without pre-existing cardiac conditions. 1

Cardiovascular Risk Evidence

• A meta-analysis by Wong et al. demonstrated a short-term risk of cardiovascular outcomes with macrolides in observational studies, estimated at 1.79 excess myocardial infarctions per 1000 patients (95% CI: 0.88 to 3.20), but this risk was not observed in randomized controlled trials 1
• No significant long-term cardiovascular risk (ranging from 30 days to three years) associated with macrolides was observed in this meta-analysis 1
• The CLARICOR study and several subsequent studies found increased risks of cardiovascular events up to a year after clarithromycin exposure, but this has not been consistently demonstrated in multiple large observational studies 1
• Williamson et al. found no statistically significant short- or long-term cardiovascular risks with clarithromycin in a large observational cohort of 66,331 adult patients 1
• The FDA drug label notes that in one clinical trial evaluating clarithromycin in patients with coronary artery disease, an increased risk of all-cause mortality was observed with a hazard ratio of 1.10 (95% CI 1.00 to 1.21) at 10-year follow-up 2

Risk Factors and Mechanisms

• Clarithromycin can cause QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes 2
• Patients with pre-existing heart conditions are at higher risk for cardiovascular events with clarithromycin use 1
• Risk factors for arrhythmias with clarithromycin include:
  • History of QT prolongation (congenital or acquired)
  • Ventricular cardiac arrhythmia
  • Hypokalemia 1
  • Concomitant use of medications that can prolong QT interval 1

Clinical Recommendations

• Clarithromycin should not be given to patients with:

  • History of QT prolongation
  • Ventricular cardiac arrhythmia including torsades de pointe
  • Hypokalemia 1

• Concomitant use of clarithromycin is contraindicated with:

  • QT-prolonging medications (astemizole, cisapride, pimozide, terfenadine)
  • Ergotamine or dihydroergotamine
  • Ticagrelor or ranolazine
  • HMG-CoA reductase inhibitors metabolized by CYP3A4 (lovastatin, simvastatin)
  • Colchicine 1, 2

• For pneumonia treatment, clarithromycin remains an effective option when appropriate:

  • For outpatients without cardiopulmonary disease or risk factors for drug-resistant S. pneumoniae, an advanced generation macrolide like clarithromycin is recommended as first-line therapy 1
  • For more complex patients, clarithromycin can be used in combination with a β-lactam 1

Monitoring Recommendations

• Perform ECG screening before initiating clarithromycin therapy in high-risk patients to exclude prolonged QTc interval 3
• Obtain a thorough medication history to identify other QT-prolonging agents that could interact with clarithromycin 3
• Discontinue clarithromycin if QTc prolongation develops during treatment 3
• Use with extreme caution in patients with known cardiac disease or history of arrhythmias 3

Efficacy in Pneumonia

• Clarithromycin has been shown to be effective in the treatment of community-acquired pneumonia with clinical cure or improvement rates of 86% 4, 5
• It is as effective as other antibiotics like cefixime, amoxicillin-clavulanic acid, and other β-lactam agents in treating community-acquired pneumonia 6, 4
• Oral clarithromycin appears to be equivalent to intravenous administration in treating moderate to severe community-acquired pneumonia when the oral route is not compromised 5

Conclusion

When prescribing clarithromycin for pneumonia, clinicians should weigh the small risk of cardiovascular events against the benefits of treatment, particularly in patients with pre-existing cardiac conditions or risk factors for QT prolongation. For most patients without cardiac risk factors, clarithromycin remains an effective and appropriate treatment option for community-acquired pneumonia.