Aralet (letrozole) coated tablets 2.5 mg. №30

Description

Ingredients:

active substance: letrozole;

1 film-coated tablet contains 2.5 mg of letrozole;

excipients: lactose, monohydrate; microcrystalline cellulose; corn starch; sodium starch glycolate (type A); silicon dioxide colloidal anhydrous; magnesium stearate;

film shell: Opadray yellow 02B38014: hypromellose (E 464), iron oxide red (E 172), iron oxide yellow (E 172), talc, macrogol, titanium dioxide (E 171).

Medicinal form. Film-coated tablets.

The main physicochemical properties: round, biconvex, film-coated, yellow tablets.

Pharmacotherapeutic group.

Means used for hormone therapy. Antagonists of hormones and similar means. Aromatase inhibitors. Letrozole. ATX code L02B G04.

Pharmacological properties.

Pharmacodynamics.

Letrozole is a non-steroidal aromatase inhibitor (estrogen biosynthesis inhibitor); anticancer drug.

If the growth of tumor tissue depends on the presence of estrogens, the elimination of the stimulatory 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 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 inhibition of estrogen biosynthesis in peripheral tissues and in tumor tissue.

Letrozole inhibits aromatase by competitively binding to the subunit of this enzyme – cytochrome P450 heme, which leads to a decrease in the biosynthesis of estrogens in all tissues.

In healthy postmenopausal women, single doses of 0.1 mg, 0.5 mg, and 2.5 mg of letrozole reduce serum estrone and estradiol levels (compared to baseline) by 75-78% and 78%, respectively . The maximum reduction is achieved after 48-78 hours.

In postmenopausal women with advanced breast cancer, the daily use of letrozole in a dose of 0.1 mg to 5 mg reduces the levels of estradiol, estrone and estrone sulfate in the blood plasma by 75-95% of the initial level. When using the drug in a dose of 0.5 mg or more, in many cases the concentrations of estrone and estrone sulfate are found to be 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. Estrogen suppression was maintained during treatment in all patients.

Letrozole is a highly specific inhibitor of aromatase activity. Violation of the synthesis of steroid hormones in the adrenal glands was not detected. No clinically significant changes in blood plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH, and renin activity were detected in postmenopausal patients treated with letrozole in 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 reduction in aldosterone or cortisol synthesis. Thus, there is no need to prescribe glucocorticoids and mineralocorticoids.

In healthy postmenopausal women, 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 detected. In postmenopausal patients who received letrozole in a daily dose from 0.1 mg to 5 mg, changes in the level of androstenedione in the blood plasma were also not noted. All this indicates that the blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are precursors of estrogens. In patients who received letrozole, there were no changes in the concentrations of luteinizing and follicle-stimulating hormones in the blood plasma, nor were there any changes in the functions of the thyroid gland, which was evaluated by the levels of thyroid-stimulating hormone T 4 _and T ₃ .

Indications.

• Adjuvant therapy of hormone-positive invasive breast cancer in early stages in postmenopausal women.
• Extended adjuvant therapy for early-stage invasive breast cancer in postmenopausal women who received standard adjuvant tamoxifen therapy for 5 years.
• First-line therapy of hormone-dependent advanced breast cancer in postmenopausal women.
•  Treatment of advanced forms of breast cancer in postmenopausal women (natural or artificially induced) after recurrence or progression of the disease, who received prior therapy with antiestrogens.
• Neoadjuvant therapy in postmenopausal women with hormone-positive, HER-2-negative breast cancer for whom chemotherapy is not suitable and urgent surgical intervention is not indicated.

The effectiveness of the drug for patients with hormone-negative breast cancer has not been proven.

Contraindications.

• Hypersensitivity to the active substance or to any other component of the drug.
• Endocrine status characteristic of the premenopausal period.
• Severe liver failure (class C on the Child-Pugh scale).
• Preoperative use of the drug if the receptor status is negative or unknown.
• Pregnancy, breastfeeding period.
• Women of reproductive age.

Dosage and Administration.

Adults, including elderly patients. The recommended dose of letrozole is 2.5 mg once a day. In adjuvant and extended adjuvant therapy, treatment with letrozole should continue for 5 years or until disease relapse occurs. In patients with metastases, letrozole therapy should be continued until signs of disease progression are evident. In the conditions of adjuvant treatment, the possibility of using a scheme of sequential therapy (letrozole for 2 years with subsequent transition to tamoxifen for 3 years) should also be considered.

In conditions of neoadjuvant treatment, Aralet therapy should be continued for 4-8 months to achieve optimal tumor reduction. If the response to treatment is insufficient, drug therapy should be stopped and planned surgical intervention should be scheduled and/or options for further treatment should be discussed with the patient.

During the preoperative treatment period, regular monitoring of disease progression is recommended. Dose correction is not required for elderly patients.

Children. The drug is not used to treat children. The safety and effectiveness of Aralet’s use in children have not been established. Available data are limited, so it is not possible to make recommendations regarding dosage.

Patients with impaired liver and/or kidney function.

For patients with mild to moderate liver damage (class A and B according to the Child-Pugh scale) or kidney damage (creatinine clearance ≥ 10 ml/min), no dose adjustment is required. Available data on patients with renal insufficiency with creatinine clearance < 10 ml/min or severe hepatic impairment are insufficient. Patients with severe hepatic impairment (Child-Pugh class C) require close monitoring.

Application method

Aralet should be taken orally regardless of food intake, as food does not affect the degree of absorption of the drug.

The missed dose should be taken as soon as the patient remembers it. However, if the patient remembers this shortly before taking the next dose (in 2-3 hours), the missed dose should be skipped and the next dose taken according to the schedule. A double dose should not be taken, as higher than proportional systemic exposure has been observed when taking a daily dose higher than the recommended 2.5 mg.

Children.

The drug is not used in children, since the effectiveness and safety of the use of letrozole for this category of patients have not been studied in clinical trials.