Drug interactions between aminophylline and Zithromax

MONITOR: Coadministration with certain macrolide antibiotics may increase the serum concentrations of theophylline, which may result in toxicity. In one case report, a pediatric patient developed seizures in association with theophylline toxicity shortly after the addition of erythromycin. The proposed mechanism is macrolide inhibition of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of theophylline. Data from pharmacokinetic studies suggest that the magnitude of the interaction is generally greatest with troleandomycin, followed by erythromycin. The interaction with clarithromycin appears to be mild and inconsistent. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4, and most studies have not found a significant effect on the pharmacokinetics of theophylline. However, a case report describes an unusual interaction with azithromycin in an elderly patient whereby reduced serum theophylline levels were repeatedly observed after the discontinuation of azithromycin. The changes were transient and did not require an adjustment in the theophylline dosage. Theophylline has been reported to decrease plasma concentrations of erythromycin by increasing its renal clearance.

MANAGEMENT: Pharmacologic response and serum theophylline levels should be monitored more closely whenever a macrolide antibiotic is added to or withdrawn from therapy, and the methylxanthine dosage adjusted as necessary. For patients with theophylline levels at the upper end of the therapeutic range (15 to 20 mcg/mL), some clinicians suggest an initial reduction of the methylxanthine dosage by 25% when given with erythromycin and 50% with troleandomycin. Patients should be advised to contact their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat.