Abstract
Oestrogens could inhibit the metabolism of drugs, such as calcineurin inhibitors, that are substrates for cytochrome P-450 microsomal enzymes. This study assessed the potential tacrolimus interaction with oral conjugated oestrogen in kidney transplant recipients who received conjugated oestrogen as prophylaxis against bleeding, before kidney biopsy. In this case-control study, 13 kidney transplant recipients who received oral conjugated oestrogen as prophylaxis against uraemic bleeding before allograft biopsy were considered as cases. Thirteen matched kidney transplant recipients with similar immunosuppressive regimen served as controls. In this study, comparisons were made between the groups regarding daily dose, blood trough concentrations and calculated concentration corrected for dose of tacrolimus at three time points of the study. All patients in the case group received conjugated oestrogen at a dose of 3.75mg/day for 4.78±0.83days. Without any change in tacrolimus dose, the blood concentration of tacrolimus increased during concomitant administration of conjugated oestrogen (from 8.10±2.85 to 12.35±4.62ng/mL; P=.11) and decreased after cessation of conjugated oestrogen (6.07±2.18ng/mL; P=.015). The calculated concentration corrected for dose of tacrolimus increased from 127.04±79.23 to 211.40±146.38 ngmLmgkg/d after conjugated oestrogen administration (P=.036). Thereafter, it decreased to 108.55±78.61 ngmLmgkg/d after cessation of oestrogen (P=.003). Only one patient experienced nausea while taking oestrogen without any change in her liver enzymes. Concomitant administration of oral oestrogen increased tacrolimus blood concentration. Hence, it is necessary to monitor tacrolimus blood levels during concomitant oestrogen therapy and for several days after oestrogen withdrawal.
Published Version
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