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at the time of writing, PharmD Student, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada; now, Clinical Pharmacist (Internal Medicine/Nephrology), Montreal General Hospital, The McGill University Health Center, Montreal, Quebec, Canada
Clinical Coordinator & Pharmacotherapeutic Specialist (Transplant/Immunology), Vancouver Coastal Health Authority; Clinical Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver
PhD Candidate, Faculty of Pharmaceutical Sciences, The University of British Columbia
Professor and Director, Doctor of Pharmacy Program, Faculty of Pharmaceutical Sciences, and Distinguished University Scholar, The University of British Columbia; Clinical Pharmacy Specialist, Children's and Women's Health Centre of British Columbia, Vancouver
Reprints: Dr. Ensom, Department of Pharmacy (0B7), Children's & Women's Health Centre of British Columbia, 4500 Oak St., Vancouver, BC V6H 3N1, Canada, fax 604/875-3735, ensom{at}interchange.ubc.ca
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, mycophenolate, sirolimus, drug interactions, CYP3A4, P-glycoprotein, and UDP-glucuronosyltransferases. 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.
Key Words: corticosteroids, cyclosporine, glucocorticoids, immunosuppressants, mycophenolate, sirolimus, tacrolimus
Published Online, July 1, 2008. www.theannals.com, DOI 10.1345/aph.1K628
THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-08-013-H01P
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