Letrozol Sandoz Filmtabletten 2.5mg 100 Stück

Description

Pharmacokinetics in special cases

Pharmacokinetic parameters of letrozole are independent of age.

• Renal impairment

In studies in postmenopausal women volunteers with renal dysfunction of various 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 the second line of therapy, no changes in pharmacokinetic parameters and systemic exposure of letrozole were observed. Taking into account the above mentioned, 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.

• Liver dysfunction

In a similar study in patients with hepatic impairment of varying severity, the 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 the study in patients with cirrhosis and severe liver dysfunction (Child-Pugh class C), an increase in AUC and T1/2 by 95% and 187%, respectively, was observed relative to healthy volunteers. Thus, increased systemic exposure of letrozole is expected in patients with breast cancer with severe liver dysfunction. However, taking into account that no increase in toxicity was observed in patients receiving letrozole in doses of 5-10 mg, dose adjustment in case of severe liver dysfunction is not justified, careful monitoring of patients in this category is necessary.

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