Letrozol coated tablets 2.5 mg. №30

Description

Letrozol coated Composition
active substance: letrozole;

1 tablet contains letrozole 2.5 mg;

auxiliary substances: microcrystalline cellulose, corn starch, magnesium stearate, lactose, colloidal silicon dioxide, sodium starch (type A), iron oxide yellow (E 172), polyethylene glycol, titanium dioxide (E 171), talc, indigo (E 132), polyvinyl alcohol, tartrazine (E 102).

Letrozol coated Dosage form
Film-coated tablets.

Basic physical and chemical properties: dark yellow round biconvex tablets, film-coated with embossing “93” on one side and “B1” – on the other.

Letrozol coated Pharmacotherapeutic group
Drugs used for hormone therapy. Hormone antagonists and similar agents. Aromatase inhibitors. Letrozole.

ATX code L02B G04.

Letrozol coated Pharmacodynamics
Letrozole is a non-steroidal aromatase inhibitor (estrogen biosynthesis inhibitor), anticancer 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, with the help of specific inhibition of the aromatase enzyme, it is possible to achieve suppression of 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. In all patients, estrogen suppression persisted during the treatment period.

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 treated with letrozole at a daily dose of 0.1-5 mg, clinically significant changes in plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH, and 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 any noticeable decrease in the synthesis of aldosterone or cortisol. Thus, there is no need to prescribe glucocorticoids and mineralocorticoids.

In healthy postmenopausal women, after a single use of letrozole at a dose 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 treated with letrozole, there were no changes in the concentrations of luteinizing hormones and folliculo hormones in the blood plasma, and there were no changes in the functions of the thyroid gland, which was assessed by the levels of thyroid stimulating hormone, T4 and T3.