erythromycin

Brand: Ery-Tab, Erythrocin, EES

Prototype Drug
Drug Class: macrolide antibiotic
Drug Family: antibiotic
Subclass: first macrolide antibiotic
Organ Systems: infectious-diseasegastrointestinal

Mechanism of Action

Reversibly binds 50S ribosomal subunit, inhibiting translocation and peptide elongation; bacteriostatic. Additionally acts as a motilin receptor agonist, stimulating gastric motility — used as a prokinetic.

50S ribosomal subunit (23S rRNA)

Indications

  • community-acquired pneumonia (atypical pathogens)
  • pharyngitis/tonsillitis (penicillin-allergic)
  • chlamydial infections in pregnancy
  • pertussis (whooping cough)
  • gastroparesis (prokinetic, off-label, low doses)
  • diphtheria and legionellosis
  • acne vulgaris (topical)

Contraindications

  • macrolide hypersensitivity
  • concurrent use of ergotamine, dihydroergotamine
  • hepatic impairment (estolate salt)
  • QTc-prolonging drugs (relative)

Adverse Effects

Common

  • GI upset (nausea, vomiting, diarrhea, abdominal cramping — most common with this agent)
  • taste disturbance
  • epigastric pain

Serious

  • hepatotoxicity (especially estolate salt)
  • QTc prolongation
  • C. difficile colitis
  • ototoxicity (high IV doses)

Pharmacokinetics (ADME)

Absorption variable: base ~25%, ethylsuccinate ~40%, enteric-coated better; food reduces absorption of base form
Distribution widely distributed; high tissue concentrations; crosses placenta
Metabolism extensive CYP3A4 hepatic metabolism; also a CYP3A4 inhibitor
Excretion primarily biliary; renal minimal
Half-life 1.5–2 hours
Onset 1–2 hours oral
Peak 1–4 hours
Duration 6 hours
Protein Binding 65–90%
Vd large

Drug Interactions

Drug / Agent Mechanism Severity
warfarin CYP3A4 inhibition increases INR; monitor closely major
statins (simvastatin, lovastatin) CYP3A4 inhibition increases statin exposure; rhabdomyolysis major
QTc-prolonging drugs additive QTc prolongation; torsades risk major
theophylline reduced theophylline clearance; toxicity risk major

Nursing Considerations

  1. GI adverse effects are the primary tolerability issue; administering with food or using the ethylsuccinate salt reduces GI intolerance.
  2. Screen for QTc-prolonging drug interactions before administering IV erythromycin; baseline ECG recommended for IV use.
  3. For gastroparesis, use very low doses (50–250 mg) to exploit the motilin agonist effect; higher doses paradoxically desensitize motilin receptors.
  4. Monitor LFTs in patients receiving prolonged courses; hepatotoxicity (cholestatic jaundice) is associated with the estolate formulation.

Clinical Pearls

  • Erythromycin was the first macrolide and remains important historically, but its GI adverse effects and numerous drug interactions (CYP3A4 inhibition) have led to widespread replacement by azithromycin and clarithromycin for most indications.
  • At subantimicrobial doses, erythromycin acts as a motilin receptor agonist and promotes gastric emptying; this prokinetic effect is used for gastroparesis but loses efficacy over days due to receptor desensitization.

Safety Profile

Pregnancy avoid
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required