LETROZOL Accord 2,5 mg Filmtabletten 1 0 1 Carefarm

Description

Pharmacokinetics in specific cases

The pharmacokinetic parameters of letrozole are independent of age.

• Renal impairment

In studies with postmenopausal female volunteers with renal impairment of varying degrees (daily creatinine clearance 9-116 ml/min) after a single dose of 2.5 mg, as well as in patients with metastatic breast cancer in second-line treatment, no changes in the pharmacokinetic parameters and systemic exposure of letrozole were observed. Given this, no dose adjustment is required in patients with impaired renal function (with creatinine clearance ≥ 10 ml/min). Data on the use of letrozole in patients with severe renal impairment with creatinine clearance <10 ml/min are limited.

• Hepatic impairment

In a similar study involving patients with varying degrees of hepatic impairment, mean AUC values in volunteers with moderate hepatic impairment (Child-Pugh class B) were 37% higher than in healthy participants, but remained within the range of values reported in participants without hepatic impairment.

In a study involving patients with cirrhosis and severe hepatic impairment (Child-Pugh class C), an increase in AUC and T1/2 of 95% and 187%, respectively, was observed compared to healthy volunteers. Therefore, increased systemic exposure of letrozole is expected in breast cancer patients with severe hepatic impairment. However, given that no increase in toxicity was observed in patients receiving letrozole at doses of 5-10 mg, dose adjustment for severe hepatic impairment is not warranted; careful monitoring of patients in this category is necessary.

According to the results of two controlled studies in patients with advanced breast cancer, no effect of renal impairment (estimated creatinine clearance 20-50 ml/min) or hepatic impairment on letrozole levels was observed.