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Purpose: Iatrogenic adrenal suppression and Cushing syndrome are well-described adverse events in patients receiving corticosteroids in combination with azole antifungals other than posaconazole (POS). Like other azoles, POS is an inhibitor of CYP3A4. Budesonide (BUD), a corticosteroid, is a substrate for CYP3A4. To date, no studies have assessed the influence of POS on corticosteroid pharmacokinetics (PK). Moreover, current labeling for POS does not include possible interactions with corticosteroids. The purpose of this report is to describe the interaction between POS and budesonide via retrospective analysis.
Methods: Retrospective review of patients receiving concurrent POS and BUD.
Results: Patients Receiving Concomitant POS and BUD
Patient and Diagnosis [POS Dose] | BUD Dose | BUD Trough Serum Concentrations* (nmol/L) | Cortisol Normal Range: 5 – 25 mcg/dL |
| 29 year old male with common variable immunodeficiency enteropathy [400 mg BID] | 3 mg QD 3 mg QD
| 4.41 7.20
| <1.0 mcg/mL <1.0 mcg/mL
|
| 7 year old male with chronic granulomatous disease colitis [300 mg TID] | 3 mg QOD
| 5.81
| <1.0 mcg/mL
|
| 59 year old female with celiac disease and brochiectasis [200 mg QID] | 3 mg TID 3 mg BID 3 mg QD
| 10.11 9.06 5.34 | <1.0 mcg/mL <1.0 mcg/mL <1.0 mcg/mL |
Conclusion: Three patients receiving concomitant BUD and POS experienced adrenal insufficiency along with BUD trough concentrations that exceeded typical peak BUD concentrations when the drug was administered without concurrent azole therapy (Table). Inhibition of budesonide metabolism via CYP3A4 by POS is the likely mechanism for this interaction. To our knowledge, this is the first report of a PK/PD interaction between POS and a corticosteroid. Accordingly, POS should be use with caution in patients receiving concurrent corticosteroids metabolized via CYP3A4. In addition, POS labeling should recognize the possibility of this interaction due to its potentially serious nature.