Corticosteroid interactions with cyclosporine, tacrolimus, mycophenolate, and sirolimus: Fact or fiction?

OBJECTIVE: To review the current clinical evidence on the effects of corticosteroid interactions with the immunosuppressive drugs cyclosporine, tacrolimus, mycophenolate, and sirolimus. DATA SOURCES: Articles were retrieved-through MEDLINE (1966-February 2008) using the terms corticosteroids, glucocorticoids, immunosuppressants, cyclosporine, tacrolimus, mycoohenolate, sirolimus, drug interactions, CYP3A4, P-glycoprotein, and UDP-glucuronoslyltrahsferases. Bibliographies were manually searched for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All, English-language studies dealing with drug interactions between corticosteroids and cyclosporine, tacrolimus, mycophenolate, and sirolimus were reviewed. DATA SYNTHESIS: Corticosteroids share. common metabolic and transporter pathways, the cytochrome P450 and P-glycoprotein (P-gp/ABCB1) systems, respectively, with cyclosporine, tacrolimus, and sirolimus. As a group, corticosteroids induce the CYP3A4 and P-gp pathways; however, a few exceptions exist and the impact on a patient's immunosuppressant regimen may be critical. Corticosteroids also have demonstrated, an induction effect on the uridine diphosphate-glucuronosyltransferase enzymes and multidrug resistance-associated protein 2 involved in mycophenolate's disposition. Successful corticosteroid withdrawal regimens have been reported; however, only few studies have examined the effects of steroid withdrawal, on the remaining immunosuppressive regimens. To date, the clinical impact of steroid withdrawal on disposition of other immunosuppressive agents is not well characterized, and reports of such drug-drug interactions are conflicting. CONCLUSIONS: While our understanding of the clinical impact of steroid-immunosuppressant interactions is limited it remains a fact that corticosteroids have complex induction and inhibition interactions with common metabolic and transport pathways. Given the complex interaction of corticosteroids on crucial metabolic enzymes and transporter proteins, monitoring of immunosuppressive agents during steroid withdrawal is warranted to ensure optimal treatment outcomes.