LETROPUREN 2,5 mg Filmtabletten

Description

Pharmacodynamics

In healthy postmenopausal women taking letrozole in single doses of 0.1 mg, 0.5 mg and 2.5 mg, a reduction in serum estrone and estradiol activity of 75-78% and 78% of baseline levels, respectively, was observed. The maximum effect was noted after 48-72 hours.

In postmenopausal patients with advanced breast cancer, daily administration of letrozole at a daily dose of 0.1 mg to 5 mg leads to a 75-95% reduction in plasma concentrations of oestradiol, oestrone and oestrone sulphate from baseline. When administered at a dose of 0.5 mg or higher, estrone and estrone sulphate concentrations remain below the threshold for most assay methods. Suppression of estrogen synthesis is maintained throughout the treatment period.

Letrozole highly specifically inhibits aromatase activity. No impairment of adrenal steroid hormone production was observed. No clinically significant changes in cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone and adrenocorticotropic hormone (ACTH) levels or plasma renin activity were observed during the use of letrozole in postmenopausal patients in the dose range of 0.1 to 5 mg. A study with ACTH after 6 and 12 weeks of treatment with letrozole at daily doses of 0.1 mg, 0.25 mg, 0.5 mg, 1 mg, 2.5 mg and 5 mg showed no impairment of aldosterone or cortisol synthesis. Additional administration of glucocorticosteroids and mineralocorticosteroids is not required.

No changes in plasma androgen (androstendione and testosterone) concentrations were observed after a single administration of letrozole at doses of 0.1 mg, 0.5 mg and 2.5 mg in healthy postmenopausal women. No changes in plasma androstendione concentrations were also observed in patients treated with letrozole at daily doses of 0.1-5 mg, indicating that blockade of estrogen biosynthesis does not lead to accumulation of androgens, which are precursors of estrogens. No changes in plasma luteinising hormone (LH) and folliculotropic hormone (FSH) levels, changes in thyroid function (thyroid hormone (TSH), triiodothyronine (T3) and thyroxine (T4)), changes in lipid profile, increased incidence of myocardial infarction and stroke were observed during the use of letrozole.