Interaction Between Omeprazole and Tacrolimus in Renal Allograft Recipients: A Clinical-Analytical Study J. Pascual, R. Marcén, O.E. Orea, M. Navarro, M.C. Alarcón, J. Ocaña, J.J. Villafruela, F.J. Burgos, and J. Ortuño ABSTRACT Omeprazole is a proton pump inhibitor with a number of pharmacokinetic drug interac- tions due to interference with cytochrome P450. Some studies show absence of relevant interaction between omeprazole and cyclosporine, but little is known about possible interactions between omeprazole and tacrolimus. In vitro studies suggest such interfer- ence, but no clinical data are available so far. We assessed interactions between omeprazole and tacrolimus among patients fulfilling two criteria: (1) renal allograft recipients receiving immunosuppression based on tacrolimus and acid-related disorder prophylaxis with omepra- zole 20 mg/d since the day of the transplant procedure and (2) stopped omeprazole when it was considered unnecessary. Fifty-one transplant recipients received concomitant immunosuppres- sion with MMF-prednisone (n = 47) or azathioprine-prednisone (n = 1), or rapamycin- prednisone (n = 2) or only prednisone (n = 1). omeprazole was stopped after 6.2  3 months of treatment. Tacrolimus doses and levels were recorded during 3 outpatient visits before omeprazole withdrawal (Pre3/Pre2/Pre1), at the withdrawal visit (Susp), and at 3 visits after withdrawal (Pos1/Pos2/Pos3). Weight gain was significant (72.5  13 kg Pre3; 73.4  13 kg Susp; 74  12.9 kg Pos3, P  .0001) and serum creatinine (SCr) decreased (1.70  0.49 mg/dL Pre3; 1.63 + 0.49 Susp; 1.58  0.48 Pos3, P  .0001). The progressive decrease in tacrolimus doses and levels was significant (ANOVA including the 7 visits 0.01 in all cases); whereas the level/dose ratio remained constant. Tacrolimus doses and levels continued a slow, progressive and significant decrease without any relevant change between visits during on versus off omeprazole. This clinical-analytical study supported the conclusion that an omeprazole–tacrolimus interaction is not clinically relevant. Despite possible competition or interaction at the molecular level, clinical management was not significantly affected in renal allograft recipients. O MEPRAZOLE IS A proton pump inhibitor widely used to prevent or treat acid-related disorders in renal transplant recipients. 1 It shows a number of pharma- cokinetic drug interactions owing to interference with cyto- chrome P450, particularly CYP2C19 isoenzyme. 2 omepra- zole inhibits the in vitro metabolism of tacrolimus by human liver microsomes, 3,4 but no clinical study is available on the relevance of such an interaction among transplant patients. PATIENTS AND METHODS We assessed the interaction between omeprazole and tacrolimus in patients fulfilling two criteria: (1) renal allograft recipients receiv- ing immunosuppression based on tacrolimus and acid-related disorder prophylaxis with omeprazole 20 mg/d from the day of the transplant procedure and (2) they stopped omeprazole when it was considered unnecessary. Fifty-one renal allograft recipients transplanted with a cadaveric graft between February 2000 and March 2003 received tacrolimus from the day of transplantation (0.2 mg/kg/d; 10 –15 ng/mL first 2 weeks and 8 –12 ng/mL thereaf- ter). Concomitant immunosuppression included MMF (1 g/d) and prednisone (n = 47), or azathioprine-prednisone (n = 1) or rapamycin-prednisone (n = 2) or only prednisone (n = 1). From the Servicios de Nefrologı´a y Urologia (J.P., R.M., M.C.A., J.O., J.J.V., J.O.), y Urologia (F.J.B.) Hospital Ramón y Cajal, (F.J.B.), Madrid, Spain, and Servicio de Nefrologı´a (O.E.O., M.N.), Hospital La Raza, México DF. Address reprint requests to Julio Pascual, Servicio de Nefro- logı´a, Hospital Ramón y Cajal, Carretera de Colmenar km 9,100, 28034 Madrid, Spain. E-mail: jpascual.hrc@salud.madrid.org 0041-1345/05/$–see front matter © 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2005.09.126 360 Park Avenue South, New York, NY 10010-1710 3752 Transplantation Proceedings, 37, 3752–3753 (2005)