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. Treatment of common forms of breast cancer in postmenopausal women if the disease progresses after previous therapy with tamoxifen or other antiestrogens.
active substance: letrozole;
1 tablet contains letrozole 2.5 mg;
Excipients: microcrystalline cellulose, corn starch, magnesium stearate, lactose monohydrate, colloidal anhydrous silica, sodium starch glycolate (type A), iron oxide yellow (E 172), macrogol, titanium dioxide (E 171, indigol) and ), polyvinyl alcohol, tartrazine (E 102).
Letrozol-TEVA Dosage form
Main physical and chemical properties: dark yellow round biconvex tablets, film-coated, embossed with 93 on one side and B1 on the other.
Letrozol-TEVA Pharmacotherapeutic group
Means used for hormone therapy. Hormone antagonists and similar drugs. Aromatase inhibitors. Letrozole.
ATX code L02B G04.
Letrozol-TEVA Pharmacological properties
Letrozole – a non-steroidal aromatase inhibitor (inhibitor of estrogen biosynthesis); antitumor drug.
In cases where the growth of tumor tissue depends on the presence of estrogen, the elimination of the stimulant effect mediated by them is a prerequisite for inhibition of tumor growth. In postmenopausal women, estrogens are produced primarily by the enzyme aromatase, which converts androgens synthesized in the adrenal glands (primarily androstenedione and testosterone) to estrone (E1) and estradiol (E2). Therefore, with the help of specific inhibition of the enzyme aromatase, it is possible to achieve inhibition of estrogen biosynthesis in peripheral tissues and in tumor tissue.
Letrozole inhibits aromatase by competitive binding to 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 of 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 in 48-78 hours.
In women with advanced postmenopausal breast cancer, daily administration of letrozole 0.1 mg to 5 mg reduces plasma estradiol, estrone and estrone sulphate levels by 75-95% from baseline. When using the drug at 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 these doses of the drug is a more pronounced inhibition of estrogen synthesis. Estrogen suppression was maintained in all patients during the treatment period.
Letrozole is a highly specific inhibitor of aromatase activity. Disorders of steroid hormone synthesis in the adrenal glands were not detected. No clinically significant changes in plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH, and renin activity were observed in postmenopausal patients treated with letrozole at a daily dose of 0.1-5 mg. Conducting an ACTH stimulation test after 6 and 12 weeks of letrozole therapy at a daily dose of 0.1 mg; 0.25 mg; 0.5 mg; 1 mg; 2.5 mg and 5 mg did not show any significant decrease in aldosterone or cortisol synthesis. Thus, there is no need to prescribe glucocorticoids and mineralocorticoids.
In healthy postmenopausal women after a single administration of letrozole in doses of 0.1 mg, 0.5 mg and 2.5 mg changes in the concentration of androgens (androstenedione and testosterone) in the blood plasma were not detected. No changes in plasma androstenedione levels were observed in postmenopausal patients receiving letrozole at a daily dose of 0.1 mg to 5 mg. All this indicates that the blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are precursors of estrogen. There were no changes in plasma concentrations of luteinizing and follicle-stimulating hormones in patients receiving letrozole, and no changes in thyroid function as measured by thyroid-stimulating hormone T4 and T3.
Absorption. Letrozole is rapidly and completely absorbed from the gastrointestinal tract (average bioavailability is 99.9%). Food slightly reduces the rate of absorption (the average time to reach the maximum concentration of letrozole in the blood (Tmax) is 1 hour when taking letrozole on an empty stomach and 2 hours – when taken with food, the average value of the maximum concentration of letrozole in the blood (Cmax) is 129 ± 20, 3 nmol / l when taken on an empty stomach and 98.7 ± 18.6 nmol / l – when taken with food), but the degree of absorption of letrozole (when estimating the area under the curve “concentration – time”) does not change. Minor changes in the rate of absorption are considered to be of no clinical significance, so letrozole can be used with or without food.