Letrozol Teva Filmtabletten 2.5mg 100 Stück

Description

Excretion

The apparent elimination half-life from blood plasma is about 2-4 days. The equilibrium concentration is reached within 2-6 weeks of daily administration of a daily dose of 2.5 mg. Some non-linearity of pharmacokinetics at daily administration of letrozole in the dose of 2.5 mg is noted, because the plasma concentration in the equilibrium state is about 7 times higher than the concentration measured after a single dose of 2.5 mg (the expected concentration in the equilibrium state is 1.5-2 times higher than after a single dose of 2.5 mg). Since the plasma concentration at the equilibrium state remains stable over time, it can be concluded that there is no prolonged cumulation of letrozole.

Linearity/nonlinearity

Pharmacokinetics were dose-proportional after single oral administration of letrozole in doses up to 10 mg (0.01 to 30 mg) and after daily administration in doses up to 1.0 mg (0.1 to 5 mg). After a single oral administration of the drug at a dose of 30 mg, a slight dose-proportional increase in the AUC value was observed. At daily doses of 2.5 mg and 5 mg, the AUC value increased 3.8-fold and 12-fold against the expected increase of 2.5-fold and 5-fold, respectively, compared with administration at a dose of 1 mg daily. Thus, the recommended dose of 2.5 mg is a borderline dose above which disproportionate overdosing becomes evident, and this phenomenon was more pronounced at the 5 mg dose. The disproportionate exceeding of dose proportionality is probably the result of saturation of metabolic clearance processes. Equilibrium values were reached 1-2 months after administration at different doses.