Does erythromycin (antibiotic) impact cholesterol levels?

Erythromycin's Impact on Cholesterol Levels

Yes, erythromycin can significantly increase cholesterol levels by inhibiting the metabolism of statins, potentially leading to elevated cholesterol and increased risk of statin-related adverse effects.

Mechanism of Interaction

Erythromycin is a potent inhibitor of the cytochrome P450 enzyme system, specifically the CYP3A4 subclass 1. This enzyme system is responsible for the metabolism of many statins, which are commonly used to lower cholesterol levels. When erythromycin is co-administered with statins, it can:

• Inhibit CYP3A4-mediated metabolism of statins like atorvastatin, lovastatin, and simvastatin 1
• Inhibit P-glycoprotein (P-gp) transport, affecting the absorption and distribution of statins 1
• Inhibit organic anion-transporting polypeptide (OATP1B1 and OATP1B3), further affecting statin pharmacokinetics 1

Research Evidence

Research has demonstrated significant interactions between erythromycin and statins:

• Erythromycin increases serum simvastatin concentrations 6.2-fold and simvastatin acid (active metabolite) concentrations 3.9-fold 2
• Erythromycin increases plasma atorvastatin concentrations by 32.5% 3

Clinical Implications

The interaction between erythromycin and statins can lead to:

1. Reduced cholesterol-lowering efficacy: By interfering with statin metabolism, erythromycin may indirectly lead to higher cholesterol levels due to reduced effective statin concentrations

2. Increased risk of statin toxicity: Higher statin concentrations can lead to:

   • Myopathy and rhabdomyolysis
   • Elevated liver enzymes
   • Other statin-related adverse effects

Management Recommendations

When prescribing erythromycin to patients on statin therapy:

• Avoid concurrent use of erythromycin with lovastatin, simvastatin, and atorvastatin whenever possible 1
• If co-administration cannot be avoided:
  • Reduce statin dosage by approximately 50-80% during erythromycin treatment 2
  • Monitor for signs of statin toxicity (muscle pain, weakness, dark urine)
  • Consider temporarily discontinuing statin therapy during short courses of erythromycin
  • Consider switching to a statin with less CYP3A4 metabolism (e.g., pravastatin, rosuvastatin, fluvastatin)

Additional Considerations

• Erythromycin also interacts with numerous other medications through the same CYP3A4 inhibition mechanism 1
• The extent of interaction shows significant interindividual variability (more than tenfold) 2
• Patients with renal or hepatic impairment may be at higher risk for adverse effects from this interaction

By understanding this significant drug interaction, clinicians can take appropriate steps to prevent adverse outcomes while maintaining effective cholesterol management.