Interactions between budesonide and Agenerase (amprenavir)
budesonide and amprenavir (Moderate Drug-Drug)
MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and systemic effects of budesonide, which is primarily metabolized by the isoenzyme. According to budesonide labeling, potent inhibitors can increase the plasma levels of budesonide several fold. For example, an 8-fold increase in the systemic exposure (AUC) has been observed during coadministration of oral budesonide with ketoconazole. In a prospective study of a cystic fibrosis center patient population, 11 of 25 patients receiving high-dose itraconazole (400 to 600 mg/day) and budesonide inhalation therapy (800 to 1600 mcg/day) were found to have adrenal insufficiency (one developed Cushing's syndrome), compared to none in a group of 12 patients treated with itraconazole alone and none in a group of 30 cystic fibrosis patients retrospectively included as controls, 24 of whom had been treated with high-dose inhaled budesonide for several years. Adrenal function improved but did not normalize in 10 of the 11 patients during a follow-up of two to ten months after discontinuation of itraconazole and institution of hydrocortisone replacement therapy.
MANAGEMENT: The possibility of increased systemic pharmacologic effects of budesonide should be considered during concomitant therapy with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, voriconazole, nefazodone, protease inhibitors, and ketolide and macrolide antibiotics. Adrenal function should be monitored regularly during chronic use of these agents, and reduction of budesonide dosage may be necessary. Systemic glucocorticoid effects of budesonide during prolonged administration may include symptoms of hypercorticism (e.g., acne, easy bruising, moon face, edema, hirsutism, buffalo hump, skin striae, glucose intolerance, irregular menstruations); adrenal suppression (which reduces patient's ability to respond to stress situations); immunosuppression; and osteoporosis.
