Supplementary treatment in postmenopausal women at an early stage of invasive breast cancer with hormone receptors. Prolonged adjuvant treatment of hormone-dependent, invasive breast cancer at an early stage, following standard supplementary treatment with Tamoxifen for 5 years. First-line treatment of advanced hormone-dependent breast cancer in postmenopausal women. Treatment of advanced breast cancer in postmenopausal or artificially induced menopausal women who have had a recurrence or progression of a neoplastic disease and who have previously been treated with antiestrogenic agents. Neoadjuvant treatment of HER-2-negative breast cancer with hormone receptors in postmenopausal women, in whom chemotherapy is not appropriate treatment, and immediate surgery is not indicated. The efficacy of the preparation has not been demonstrated in patients with breast cancer without hormone receptors.
Composition:
1 tabl powl. contains: 2.5 mg letrozole. The drug contains lactose.
Action:
Anti-cancer drug - a non-steroidal aromatase inhibitor (an inhibitor of estrogen biosynthesis). The inhibition of tumor growth by estrogens is of fundamental importance in cancer therapy, in the case where the growth of cancerous tissue depends on the presence of estrogens and endocrine treatment is used. The drug inhibits aromatase by competing for the binding site in the heme group of the aromatase-cytochrome P-450 complex. This leads to the reduction of estrogen biosynthesis in all tissues in which aromatase is present (also in tumor tissue). Letrozole is highly specific in inhibiting aromatase activity. In postmenopausal patients, daily doses of letrozole 0.1-5 mg do not cause changes in cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone and ACTH in plasma, plasma renin activity, androstenedione, LH and FSH levels, or thyroid function. Letrozole is quickly and completely absorbed from the gastrointestinal tract (food slightly reduces the rate of absorption). The average absolute bioavailability is 99.9%. The drug is associated with plasma proteins in approximately 60%, mainly with albumin. The concentration of letrozole in erythrocytes accounts for approximately 80% of the plasma concentration. The main route of elimination of letrozole is metabolic transformation to an inactive carbinol metabolite; CYP3A4 and CYP2A6 participate in it. Letrozole is excreted mainly in the urine. T0,5 in the final phase of elimination is 2 days. Steady state is achieved within 2-6 weeks.
Contraindications:
Hypersensitivity to letrozole or other components of the drug. Pre-menopausal state. Pregnancy and breastfeeding.
Precautions:
The safety and efficacy of letrozole in children and adolescents up to 17 years have not been established, and the drug is not recommended for use in this age group. In patients with non-postmenopausal status, LH, FSH and / or estradiol should be tested prior to initiation of therapy to clearly determine the endocrine status. The use of the preparation has not been studied in sufficient numbers of patients with renal insufficiency with a creatinine clearance <10 ml / min - the benefit / risk ratio should be carefully considered before the medicine is used. Particularly with caution (after careful consideration of the benefit-risk ratio), patients with severe hepatic impairment (Child-Pugh C) should be used, due to the increased concentration of letrozole in the blood and slower elimination of it from the body. Patients with a history of osteoporosis and / or a history of osteoporosis or an increased risk of osteoporosis should have a bone density test prior to initiation of adjuvant or prolonged adjuvant treatment and should be followed to assess the development of osteoporosis during and after treatment. If appropriate, prophylaxis or treatment of osteoporosis should be recommended and monitored regularly. The drug contains lactose - tabl. should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
Patients who may become pregnant (ie women in the perimenopausal or early postmenopausal period) should be informed about the need to perform a pregnancy test and the need to use effective contraception until the post-menopausal state is fully established. The preparation is contraindicated for use during pregnancy and breast-feeding.
Side effects:
Very common: hypercholesterolemia, increased sweating, joint pain, flushing, fatigue (including asthenia).Common: hypertension, lack of appetite, increased appetite, depression, headache, dizziness, nausea, vomiting, indigestion, constipation, abdominal pain, diarrhea, alopecia, rash (including erythematous, maculopapular, resembling psoriasis, vesicular), dry skin, muscle aches, bone pain, osteoporosis, bone fractures, peripheral edema, vaginal bleeding, weight gain. Uncommon: urinary tract infections, cancer pain (not for adjuvant treatment and prolongation of adjuvant treatment), leukopenia, general edema, anxiety, including nervousness and irritability, drowsiness, insomnia, impaired memory, improper sensation, including paresthesia, hypoesthesia, taste disorders, cerebrovascular accident, cataracts, eye irritation, blurred vision, palpitations, tachycardia, thrombophlebitis (including superficial and deep vein thrombophlebitis), ischemic cardiac events, dyspnea, cough, stomatitis, dry mucous membranes oral cavity, increased liver enzymes, pruritus, urticaria, arthritis, increased urinary frequency, vaginal discharge, vaginal dryness, breast pain, fever, dry mucous membranes, thirst, weight loss. Rare: pulmonary embolism, arterial thrombosis, ischemic stroke. Not known: hepatitis, anaphylactic reactions, angioedema, toxic epidermal necrolysis, erythema multiforme.
Dosage:
Orally. Adult and elderly patients: 2.5 mg once a day. In adjuvant therapy and prolonged adjuvant treatment, treatment should be continued for 5 years or until tumor disease returns. In patients with advanced or metastatic breast cancer, treatment should be continued until evidence shows that the cancer process has progressed. In adjuvant therapy, a sequential therapy regimen (letrozole for 2 years followed by tamoxifen for 3 years) may also be considered. In the neoadjuvant setting, treatment with letrozole can be continued for 4 to 8 months to achieve optimal tumor reduction. If there is not enough, stop taking the medicine and schedule the surgery and (or) discuss with the patient further treatment options. No dosage adjustment is necessary for patients with renal impairment with creatinine clearance (CCr) ≥10 ml / min. There is insufficient data on the use of letrozole in patients with CCr <10 ml / min and in patients with severe hepatic impairment. The drug should be taken with or without food.
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