“Potential drug-drug interaction between dicloxacillin and tacrolimus in liver transplant recipients; two case reports”

Sufficient immunosuppression is paramount to preserve graft function and avoid rejection following transplantation. Tacrolimus is the cornerstone in novel immunosuppression but has a narrow therapeutic window and is susceptible to drug-drug interactions through multiple pharmacological pathways. With these case reports, we aim to shed light on a previously undescribed interaction between tacrolimus and the commonly used antibiotic dicloxacillin. Two liver transplant recipients were concomitantly treated with tacrolimus and dicloxacillin, which potentially caused sub-therapeutic tacrolimus levels. A 2 to 2.5-fold increase in tacrolimus dosage was required to maintain therapeutic levels of serum tacrolimus during treatment with dicloxacillin and one to two weeks after discontinuation. Dicloxacillin appears to be a moderate inducer of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), which could explain the observed interaction. The findings closely follow a known interaction with a similar drug, flucloxacillin, through the CYP3A4 pathway. Caution is warranted when dicloxacillin is administered in transplanted patients who are immunosuppressed using tacrolimus. Tacrolimus levels should be monitored closely; not only during dicloxacillin therapy, but also in the weeks following discontinuation.