Challenges in optimizing tacrolimus therapy in patients treated with rifampin: A case series

Tacrolimus is a cornerstone immunosuppressant in transplantation medicine with a narrow therapeutic window. Drug-drug interactions with strong CYP3A4 and P-glycoprotein modulators, such as rifampin and azole antifungals, significantly alter tacrolimus exposure and complicate therapy. Two transplant cases illustrates the impact of rifampin on tacrolimus pharmacokinetics. In one case, the tacrolimus dosage had to be increased to 120 mg/day during rifampin coadministration to maintain therapeutic concentrations, with a concentration-to-dose ratio (CDR) as low as 0.11 μg/L/mg. In both cases, cessation of rifampin led to a delayed but significant rise in tacrolimus levels, requiring substantial dose reductions within 7-15 days. These cases highlight the extreme variability in tacrolimus metabolism under the influence of rifampin and emphasize the need for daily therapeutic drug monitoring when starting, continuing and discontinuing rifampin. A multidisciplinary approach is essential and, when possible, the tacrolimus-rifampin combination should be avoided.