Major
Established
Description
Carbamazepine dramatically reduces cyclosporine plasma levels through potent CYP3A4 induction, placing transplant patients at severe rejection risk.
Mechanism
Carbamazepine is a potent CYP3A4 inducer; cyclosporine is extensively metabolized by CYP3A4, and co-administration can reduce cyclosporine AUC by 50–80%.
Clinical Significance
Sub-therapeutic cyclosporine levels can lead to acute organ rejection in transplant recipients; this is a well-documented clinically dangerous interaction.
Management
Avoid carbamazepine in transplant patients on cyclosporine; if anticonvulsant therapy is required, select a non-enzyme-inducing AED.