Mô tả
Fluconazole markedly inhibits CYP3A4-mediated tacrolimus metabolism, causing 2- to 4-fold elevations in tacrolimus trough levels and substantial risk of nephrotoxicity and neurotoxicity.
Cơ chế
Fluconazole is a potent CYP3A4 and CYP2C19 inhibitor; tacrolimus is almost entirely metabolised by intestinal and hepatic CYP3A4, so inhibition sharply reduces first-pass and systemic clearance.
Ý nghĩa lâm sàng
Case series and prospective studies consistently demonstrate tacrolimus trough levels rising 2–4-fold within days of starting fluconazole, with associated acute kidney injury and neurotoxicity.
Xử trí
Reduce tacrolimus dose empirically by 50% or more when initiating fluconazole; monitor tacrolimus levels every 2–3 days and adjust dose to maintain target trough; consider prophylactic dose reduction before antifungal is started.