Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

• Published in: American journal of transplantation Vol. 13; no. 2; pp. 474 - 484
• Main Authors: Shihab, F. S., Lee, S. T., Smith, L. D., Woodle, E. S., Pirsch, J. D., Gaber, A. O., Henning, A. K., Reisfield, R., Fitzsimmons, W., Holman, J.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01-02-2013; Elsevier Limited
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Black or African American; Body Mass Index; Corticosteroid withdrawal; Cytomegalovirus; Double-Blind Method; Female; Humans; Hyperkalemia - metabolism; kidney transplantation; Kidney Transplantation - methods; Kidneys; Male; Medical sciences; Middle Aged; mycophenolate mofetil; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - analogs & derivatives; pharmacokinetics; Pharmacology. Drug treatments; Prospective Studies; Renal Insufficiency - ethnology; Renal Insufficiency - therapy; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; tacrolimus; Tacrolimus - administration & dosage; Transplants & implants; Mofetil; Mycophenolic acid; Calcineurin inhibitor; Multicenter study; Homotransplantation; Kidney; Randomization; Surgery; Treatment withdrawal; Corticosteroid withdrawal; Graft; Antiviral; Clinical trial; Protein synthesis inhibitor; Corticosteroid; Enzyme; IMP dehydrogenase; Enzyme inhibitor; Lactone; Exposure; Macrolide; Immunomodulator; Antibiotic; Treatment; Urinary system; Tacrolimus; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Inosine monophosphate dehydrogenase inhibitor; Antibacterial agent; Pharmacokinetics; Kidney transplantation
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2012.04327.x

As corticosteroid‐sparing protocols are increasingly utilized in kidney transplant recipients, it is crucial to understand potential drug interactions between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting. This prospective, multicenter, randomized, double‐blind study included 397 patients who were randomized on posttransplant day 8 to receive either placebo (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two posttransplant were significantly greater in the CSWD group whereas TAC doses were comparable to the CCS group. This interaction was not observed in the African American subgroup. Higher serum creatinine and potassium levels were also observed in the CSWD group. MMF dose was significantly reduced in the CSWD group by the investigators because of decreased WBC counts, mostly outside of study protocol criteria, despite similar incidence of neutropenia and reported cytomegalovirus infection. Understanding TAC and MMF exposure in the context of corticosteroid‐sparing protocols should allow for improved dosing of immunosuppressants and better management of posttransplant patients.
In kidney transplant recipients, withdrawal of corticosteroids results in an increase in tacrolimus trough level and is associated with reduced mycophenolate mofetil dose.