SERIOUS INTERACTION BETWEEN MIBEFRADIL, AND TACROLIMUS

Background/aims. Tacrolimus is metabolized by cytochrome P450 3A4 and 2D6 and has a narrow therapeutic range. We report a serious kinetic in teraction between tacrolimus and mibefradil, a potent cytochrome P450 inhibitor. Case report. A 62-year-old women who had undergone liver tr ansplantation was treated with tacrolimus for immunosuppression. For c ontrol of blood pressure, the patient was treated with nifedipine. She developed ankle edema, and nifedipine was replaced by mibefradil. Fou r days later, she presented with mental confusion, renal failure, and hyperglycemia, compatible with tacrolimus toxicity. In agreement with this assumption, the tacrolimus blood concentration was 100 ng/ml. Mib efradil and tacrolimus were both stopped, and the patient recovered wi thin 1 week. Eight days after stopping mibefradil, tacrolimus was rest arted at the same dosage and the subsequent plasma concentrations rema ined in the therapeutic range. Conclusions. Mibefradil increases the t acrolimus blood concentration by inhibiting its metabolism and should, therefore, not be used in patients treated with tacrolimus.