Major
Established
Description
Phenytoin is a strong CYP3A4 inducer that can reduce tacrolimus exposure by more than 50%, putting transplant patients at risk for graft rejection.
Mécanisme
Phenytoin induces hepatic and intestinal CYP3A4 as well as P-glycoprotein, accelerating tacrolimus metabolism and reducing its bioavailability.
Signification clinique
Case reports and pharmacokinetic studies confirm clinically significant reductions in tacrolimus AUC with concomitant phenytoin, leading to documented rejection events.
Prise en charge
Closely monitor tacrolimus trough levels when phenytoin is added or discontinued; consider alternative anticonvulsants (e.g., levetiracetam) that do not induce CYP3A4 in transplant patients.