tacrolimus and fluconazole

Fluconazole is a potent inhibitor of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, the primary enzymes/transporters responsible for tacrolimus metabolism and efflux. Inhibition leads to increased tacrolimus systemic exposure.

Increased tacrolimus concentrations can precipitate dose-related toxicities such as nephrotoxicity, neurotoxicity (tremor, headache), hyperkalaemia, and increased risk of infections. Symptoms may be subtle initially.

Avoid co-prescription if possible. If unavoidable, reduce the tacrolimus dose, typically by 50-70%, and monitor tacrolimus trough concentrations frequently (e.g., every 2-3 days) until stable, then adjust accordingly. Monitor renal function, electrolytes, and signs of toxicity. Fluconazole should be stopped or changed to an alternative if possible.

Well established, supported by numerous pharmacokinetic studies and case reports. This interaction is widely recognised in clinical guidelines and prescribing information.