Drug Interactions between aminophylline and rofecoxib

MONITOR: The coadministration with rofecoxib may increase the plasma concentrations of theophylline. The proposed mechanism is rofecoxib inhibition of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of theophylline. According to the manufacturer, rofecoxib (12.5 mg, 25 mg or 50 mg orally once daily for 7 days) increased the area under the plasma concentration-time curve (AUC) of theophylline (300 mg single dose) by 38% to 60% in a group of healthy subjects.

MANAGEMENT: Caution is advised during coadministration of theophylline with rofecoxib. Theophylline plasma levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of rofecoxib therapy in patients who are stabilized on their theophylline regimen. Patients should be advised to notify their physician if they experience signs of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, seizures, palpitations, and cardiac arrhythmia.