Drug interactions between Entocort EC and nelfinavir

nelfinavir ↔ budesonide

Applies to:nelfinavir and Entocort EC (budesonide)

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. The lowest effective dosage of budesonide should be used, and further adjustments made as necessary according to therapeutic response and tolerance. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if budesonide is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma). Systemic glucocorticoids may be necessary until adrenal function recovers.