A clinical study in liver-transplant patients has shown that no pharmacokinetic interaction occurs when adefovir dipivoxil 10 mg once daily is administered concomitantly with tacrolimus, an immunosuppressant which is predominantly metabolised via the CYP450 system. Nevertheless, given that tacrolimus can affect renal function, close monitoring is recommended when coadministered with adefovir dipivoxil. The renal function of these patients should be closely monitored with a frequency tailored to the individual patient's medical condition.

The pharmacokinetics of adefovir have been evaluated in post-liver transplantation patients following multiple dose administration of Hepsera (10 mg once daily) in combination with tacrolimus (N=16). Adefovir did not alter the pharmacokinetics of tacrolimus. The pharmacokinetics of adefovir were unchanged when Hepsera was coadministered with tacrolimus (based on cross study comparison). Chronic administration of Hepsera (10 mg once daily) may result in delayed nephrotoxicity. The overall risk of nephrotoxicity in patients with adequate renal function is low. However, this is of special importance in patients at risk of or having underlying renal dysfunction and patients taking concomitant nephrotoxic agents such as tacrolimus. It is recommended that creatinine clearance is calculated in all patients prior to initiating therapy with Hepsera.

Non-HBV-infected post-transplant recipients (n=16) with stable hepatic and renal function on a stable daily dose of tacrolimus (2-10 mg total daily dose) were studied before and after co-administration of adefovir 10 mg daily for 14 days. The AUC, Cmax and median elimination half-life of tacrolimus were not significantly altered by co-administration of adefovir. Adefovir PK parameters were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period.