Femara 2,5 mg ACA Müller

Description

Pharmacodynamics

Letrozole has anti-estrogenic activity, selectively inhibiting aromatase (an estrogen synthesis enzyme) through highly specific competitive binding to a subunit of this enzyme, the cytochrome P450 gene. It blocks estrogen synthesis in both peripheral and tumour tissues.

In postmenopausal women, oestrogens are mainly formed by the enzyme aromatase, which converts androgens synthesised in the adrenal glands (mainly androstendione and testosterone) into oestrone and oestradiol.

Daily administration of letrozole at a daily dose of 0.1-5 mg leads to a reduction in plasma concentrations of oestradiol, oestrone and oestrone sulphate by 75-95% of the initial content. The suppression of estrogen synthesis is maintained throughout the treatment period.

No impairment of steroid hormone synthesis in the adrenal glands is observed during the use of letrozole in the dose range 0.1 to 5 mg, and the adrenocorticotropic hormone (ACTH) test shows no impairment of aldosterone or cortisol synthesis. Additional administration of glucocorticosteroids and mineralocorticosteroids is not required.

Blockade of oestrogen biosynthesis does not lead to accumulation of androgens, which are precursors of oestrogen. No changes in plasma concentrations of luteinising and folliculotropic hormones, changes in thyroid function, changes in lipid profile, increased incidence of myocardial infarction and stroke were observed during letrozole treatment.

Against the background of letrozole treatment, the incidence of osteoporosis increased slightly (6.9 per cent versus 5.5 per cent with placebo). However, the incidence of bone fractures in patients receiving letrozole did not differ from that in healthy individuals of the same age.

Adjuvant therapy with letrozole in early-stage breast cancer reduces the risk of recurrence, increases 5-year disease-free survival and reduces the risk of secondary cancers.

Extended adjuvant therapy with letrozole reduces the risk of recurrence by 42%. A significant disease-free survival benefit was observed in the letrozole-treated group, irrespective of lymph node involvement. Treatment with letrozole reduced mortality in patients with lymph node involvement by 40%. Extended adjuvant therapy with letrozole after 5 years of tamoxifen treatment resulted in a significant reduction in the risk of progression and development of contralateral breast cancer compared with placebo.