Adjuvant therapy for hormone-positive breast cancer in early stages in postmenopausal women. Extended adjuvant therapy for early-stage breast cancer in postmenopausal women who received standard adjuvant therapy with tamoxifen. Treatment of common forms of breast cancer in postmenopausal women as a first-line drug.
active substance: letrozole;
1 coated tablet contains 2.5 mg letrozole;
excipients: lactose, corn starch, hypromellose, microcrystalline cellulose, sodium starch (type A), colloidal silicon dioxide, magnesium stearate;
film shell: hypromellose, titanium dioxide (E 171), yellow iron oxide (E 172), polyethylene glycol 400, talc, purified water.
Letrozol Dosage form
Basic physical and chemical properties: round biconvex tablets of yellow color, smooth on both sides, film-coated.
Letrozol Pharmacotherapeutic group
Drugs used for hormone therapy. Hormone antagonists and similar agents. Aromatase inhibitors. Letrozole. ATX code L02B G04.
Letrozole is a non-steroidal aromatase inhibitor (estrogen biosynthesis inhibitor), an antineoplastic drug.
In cases where the growth of tumor tissue depends on the presence of estrogens, the elimination of the stimulating effect mediated by them is a prerequisite for suppressing tumor growth. In postmenopausal women, estrogens are formed mainly with the participation of the aromatase enzyme, which converts androgens, which are synthesized in the adrenal glands (primarily androstenedione and testosterone), into estrone (E1) and estradiol (E2). Therefore, by specifically inhibiting the aromatase enzyme, it is possible to suppress estrogen biosynthesis in peripheral tissues and in tumor tissue.
Letrozole inhibits aromatase by competitive binding with a subunit of this enzyme – cytochrome P450 heme, which leads to a decrease in estrogen biosynthesis in all tissues.
In healthy postmenopausal women, a single dose of letrozole, which is 0.1 mg, 0.5 mg and 2.5 mg, reduces serum estrone and estradiol levels (compared to baseline) by 75-78% and 78% respectively . The maximum reduction is achieved after 48-78 hours.
In women with advanced postmenopausal breast cancer, daily use of letrozole at a dose of 0.1 mg to 5 mg reduces plasma levels of estradiol, estrone and estrone sulfate by 75-95% of baseline. When using the drug in a dose of 0.5 mg or more, in many cases, the concentrations of estrone and estrone sulfate are below the sensitivity limit of the method used to determine hormones. This indicates that with the help of these doses of the drug, a more pronounced inhibition of estrogen synthesis is achieved. The inhibition of estrogen was maintained throughout treatment in all patients.
Letrozole is a highly specific inhibitor of aromatase activity. Disruption of the synthesis of steroid hormones in the adrenal glands was not found. In postmenopausal patients who were treated with letrozole in a daily dose of 0.1-5 mg, clinically significant changes in plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH (ACTH), as well as renin activity were not detected … The ACTH stimulation test after 6 and 12 weeks of therapy with letrozole at a daily dose of 0.1 mg, 0.25 mg, 0.5 mg, 1 mg, 2.5 mg and 5 mg did not reveal a single noticeable decrease in the synthesis of aldosterone or cortisol. Thus, there is no need to prescribe glucocorticoids and mineralocorticoids.
In healthy postmenopausal volunteers after a single use of letrozole in doses of 0.1 mg, 0.5 mg and 2.5 mg, no changes in the concentration of androgens (androstenedione and testosterone) in the blood plasma were found. In postmenopausal patients who received letrozole in a daily dose of 0.1 mg to 5 mg, no changes in the level of androstenedione in the blood plasma were also observed. All this indicates that the blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are estrogen precursors. In patients receiving letrozole, there were no changes in the concentration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the blood plasma, and there were no changes in the function of the thyroid gland, assessed by the levels of thyroid-stimulating hormone T4 and T3.
Letrozole is rapidly and completely absorbed from the gastrointestinal tract (the average bioavailability is 99.9%). Food slightly reduces the absorption rate (the average time to reach the maximum concentration of letrozole in the blood (tmax) is 1 hour when taking the drug on an empty stomach and 2 hours when taken with food; the average value of the maximum concentration (max) of letrozole in the blood is 129 ± 20 3 nmol / L when taken on an empty stomach and 98.7 ± 18.6 nmol / L – when consumed with food), however, the degree of absorption of letrozole (assessed by the area under the concentration-time curve (AUC)) does not change. Minor changes in the rate of absorption are regarded as having no clinical significance, so letrozole can be taken regardless of food intake.