Major
Established
Descrição
Carbamazepine, a potent CYP3A4 inducer, substantially decreases tacrolimus blood concentrations, risking acute rejection in transplant recipients.
Mecanismo
Carbamazepine upregulates CYP3A4 and P-glycoprotein expression in the gut wall and liver, increasing tacrolimus presystemic metabolism and efflux, thereby reducing AUC by 50–90%.
Significância Clínica
Published case reports document sub-therapeutic tacrolimus troughs and acute rejection episodes within 1–2 weeks of starting carbamazepine.
Conduta
Avoid combination when possible; if co-administration is necessary, monitor tacrolimus troughs every 3–4 days, anticipate large dose increases (up to 3-fold), and taper tacrolimus carefully when carbamazepine is withdrawn.