theophylline and erythromycin

Erythromycin inhibits the cytochrome P450 enzymes CYP1A2 and CYP3A4, which are responsible for the metabolism of theophylline. This inhibition reduces theophylline clearance, leading to increased plasma concentrations and a prolonged half-life.

Theophylline toxicity can manifest as nausea, vomiting, diarrhoea, restlessness, tachycardia, cardiac arrhythmias, and, in severe cases, seizures. The risk is particularly high in patients with pre-existing cardiac disease or those taking high doses.

Avoid 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.

This interaction is well established and widely documented in the literature. It is included in major drug interaction compendia and has been confirmed by numerous case reports and pharmacokinetic studies.