Erythromycin × Theophylline

An erythromycin metabolite inhibits the liver enzyme CYP3A (CYP3A3 in the label), so theophylline is cleared more slowly: according to the US Food and Drug Administration (FDA) theophylline label, theophylline levels rise by about 35%. At high theophylline doses this rise can reach toxic concentrations (erythromycin SmPC). The effect also runs the other way: with oral erythromycin, erythromycin levels fall by a similar amount and may become subtherapeutic (erythromycin SmPC and theophylline FDA label).

Early signs of excess theophylline: nausea, vomiting, especially repeated, headache, insomnia. At high levels: persistent vomiting, cardiac arrhythmias and intractable seizures that can be fatal. With oral erythromycin, erythromycin levels may fall below the therapeutic range and the infection may respond less well.

The pair is not banned, but the theophylline dose is guided by blood levels. When erythromycin is added, theophylline levels are followed and the dose is reduced to avoid toxic concentrations (erythromycin SmPC). The US Food and Drug Administration (FDA) theophylline label warns that if the total daily dose is not reduced in time, severe and potentially fatal toxicity can occur; levels are measured both when an interacting drug is added and when it is stopped. In most patients steady state is reached after about 3 days of regular dosing (theophylline FDA label). If nausea or vomiting appear, the next theophylline dose is withheld and a level is measured at once (theophylline FDA label). After erythromycin is stopped, theophylline levels fall and the dose is increased back (theophylline FDA label).