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Drug Reference

erythromycin

macrolide antibiotic· Brands: Erythrocin, E.E.S., Eryc, RobimycinIVPOTOP

Mechanism of action
Erythromycin binds to the 50S subunit of the bacterial ribosome, thereby inhibiting protein synthesis. It is usually bacteriostatic, although it can be bactericidal at higher concentrations. It has activity against many gram-positive bacteria, some gram-negative organisms, and atypical pathogens such as Mycoplasma pneumoniae and Legionella pneumophila.
Pharmacokinetics
Erythromycin is well absorbed after oral administration, but bioavailability is variable. It is extensively bound to plasma proteins. It is metabolised in the liver by CYP3A4 to inactive metabolites. It is excreted mainly in bile, with a small amount in urine. The elimination half-life is approximately 1.5 to 2 hours, but may be prolonged in hepatic impairment.
Indications & dosing

Community-acquired pneumonia

Take for 7-14 days; give with food to reduce GI upset.

  • adult · PO: 250–500 mg QID · Take for 7-14 days; give with food to reduce GI upset.

Pertussis

Treat for 14 days; also used for prophylaxis after exposure.

  • adult · PO: 500 mg QID · Treat for 14 days; also used for prophylaxis after exposure.

Chlamydia trachomatis infection

Alternative to azithromycin; treat for 7 days.

  • adult · PO: 500 mg QID · Alternative to azithromycin; treat for 7 days.

Skin and soft tissue infections

Take with food to reduce GI upset; duration depends on severity.

  • adult · PO: 250–500 mg QID · Take with food to reduce GI upset; duration depends on severity.

Severe infections (IV)

Slow IV infusion; switch to oral therapy when clinically appropriate.

  • adult · IV: 500 mg QID · Slow IV infusion; switch to oral therapy when clinically appropriate.
Contraindications & precautions
  • Hypersensitivity to erythromycin or other macrolides · Cross-sensitivity may occur.
  • Concomitant use of drugs that are potent CYP3A4 inhibitors and prolong QT interval (e.g., cisapride, terfenadine, astemizole, pimozide) · Risk of serious ventricular arrhythmias.
  • Pre-existing QT interval prolongation or significant electrolyte disturbances (hypokalaemia, hypomagnesaemia) · May increase risk of torsades de pointes.
  • Severe hepatic impairment · Erythromycin is metabolised by the liver; dose adjustment or avoidance may be necessary.
  • Use with caution in patients with hepatic impairment; monitor liver function.
  • Caution in patients with QT prolongation, electrolyte disturbances, or those taking other QT-prolonging drugs.
  • Caution with drugs that are CYP3A4 substrates or inhibitors due to potential interactions.
  • Caution in myasthenia gravis; erythromycin may worsen symptoms.
  • Use in pregnancy only if clearly needed; consult local guidelines.
  • In neonates, weigh risks and benefits; monitor for pyloric stenosis.
Adverse effects
  • Gastrointestinal disturbances (nausea, vomiting, abdominal pain, diarrhoea)
  • QT interval prolongation and ventricular arrhythmias (e.g., torsades de pointes)serious
  • Hepatotoxicity (cholestatic jaundice, hepatitis)serious
  • Allergic reactions, including anaphylaxisserious
  • Ototoxicity (reversible hearing loss) with high dosesserious
  • Infantile hypertrophic pyloric stenosis in neonatesserious
Interactions
  • carbamazepinemajorAvoid co-prescription if possible. If combination is necessary, consider using an alternative macrolide such as azithromycin which has less effect on CYP3A4. If erythromycin must be used, monitor carbamazepine plasma levels closely (e.g., every 2 to 3 days initially) and adjust the carbamazepine dose accordingly. Monitor the patient for signs of carbamazepine toxicity.
  • digoxinmajorMonitor serum digoxin concentrations and renal function before and after starting erythromycin. Watch for signs of digoxin toxicity. A digoxin dose reduction may be needed, and alternative antibiotics should be considered if possible. If erythromycin is used, adjust the digoxin dose according to the measured levels.
  • simvastatincontraindicatedCo-administration is contraindicated. If erythromycin is required, alternative lipid-lowering therapy should be considered, such as pravastatin or rosuvastatin, which are less dependent on CYP3A4 metabolism. If temporary treatment with erythromycin is unavoidable, simvastatin should be withheld during the course of antibiotic therapy.
  • theophyllinemajorAvoid co-prescription if possible. If combination therapy is unavoidable, reduce the theophylline dose by approximately 30 to 50% and monitor serum theophylline concentrations closely, especially during the first few days of erythromycin therapy and after its discontinuation. Monitor for signs of theophylline toxicity.
  • atorvastatinmajorAvoid co-prescription when possible. If the combination is necessary, consider using a less interacting macrolide (e.g., azithromycin) or reduce the atorvastatin dose. Monitor patients for muscle symptoms and check creatine kinase if symptoms occur.
  • warfarinmajorAvoid concomitant use if possible. If co-prescription is necessary, monitor the INR closely at baseline and within 3 to 5 days of starting erythromycin. Consider a reduction in warfarin dose and continue monitoring after erythromycin is stopped.
  • cyclosporinemajorAvoid concomitant use if possible. If co-prescription is necessary, consider a non-interacting macrolide (e.g., azithromycin). When erythromycin is required, closely monitor cyclosporine trough levels, renal function, and blood pressure. Expect to reduce the cyclosporine dose, often by 25-50%, and adjust based on levels. Monitor levels frequently during therapy and for several days after stopping erythromycin.
Renal & hepatic adjustment
  • Hepatic impairment (moderate): Use with caution; monitor liver function.
  • Hepatic impairment (severe): Avoid or reduce dose; consider alternative antibiotic. (avoid)
Monitoring, pregnancy & toxicity
  • Liver function tests · Baseline and periodically during therapy
  • ECG (QT interval) · In patients at risk of QT prolongation
  • Clinical response and adverse effects · Throughout therapy
  • Pregnancy: Erythromycin is generally considered safe in pregnancy; it is a preferred macrolide when treatment is required. Use only if clearly indicated, but no fetal harm has been demonstrated.
  • Toxicity: QT prolongation and torsades de pointes · Discontinue erythromycin, correct electrolyte imbalances, and monitor ECG.
  • Toxicity: Hepatotoxicity (e.g., cholestatic jaundice) · Discontinue therapy, monitor liver function, and provide supportive care.
  • Toxicity: Gastrointestinal upset (nausea, vomiting, diarrhoea) · Symptomatic management; consider dose reduction or alternative antibiotic.
  • Toxicity: Ototoxicity (hearing loss, tinnitus), especially at high doses · Discontinue therapy and consider audiometry; symptoms are usually reversible.
Clinical notes
Erythromycin is used to treat respiratory tract infections, skin and soft tissue infections, and atypical pneumonias. It is also used as a prokinetic agent for gastroparesis. Common adverse effects include gastrointestinal disturbances such as nausea, vomiting, and diarrhoea. It can cause QT prolongation and is associated with drug interactions through CYP3A4 inhibition. Resistance among common pathogens is increasing.

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BNF; local formulary