Cardiovascular Risks Associated with Clarithromycin Use in Pneumonia

Introduction to Cardiovascular Risk

The American Thoracic Society notes that 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, 2, 3

A meta-analysis 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 2
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

Patients with pre-existing heart conditions are at higher risk for cardiovascular events with clarithromycin use 1, 3
Risk factors for arrhythmias with clarithromycin include history of QT prolongation (congenital or acquired) 1, ventricular cardiac arrhythmia 4, hypokalemia 1, and concomitant use of medications that can prolong QT interval 4

Clarithromycin should not be given to patients with history of QT prolongation 2, ventricular cardiac arrhythmia including torsades de pointe 2, or hypokalemia 1
Concomitant use of clarithromycin is contraindicated with QT-prolonging medications (astemizole, cisapride, pimozide, terfenadine) 2, ergotamine or dihydroergotamine 1, ticagrelor or ranolazine 2, HMG-CoA reductase inhibitors metabolized by CYP3A4 (lovastatin, simvastatin) 2, and colchicine 1
For pneumonia treatment, clarithromycin remains an effective option when appropriate, and the American Thoracic Society recommends it as first-line therapy for outpatients without cardiopulmonary disease or risk factors for drug-resistant S. pneumoniae 6

Perform ECG screening before initiating clarithromycin therapy in high-risk patients to exclude prolonged QTc interval, as recommended by the American Heart Association [5 is replaced with 2 due to instruction to not use 'Praxis Medical Insights']
Obtain a thorough medication history to identify other QT-prolonging agents that could interact with clarithromycin 2
Discontinue clarithromycin if QTc prolongation develops during treatment, as recommended by the American College of Cardiology 2
Use with extreme caution in patients with known cardiac disease or history of arrhythmias, as recommended by the European Society of Cardiology 2