Supplementary treatment of invasive early stage breast cancer in postmenopausal women who have been found to have hormone receptors. Prolonged adjuvant treatment of hormone-dependent invasive breast cancer after previous standard supplementary treatment with Tamoxifen lasting 5 years in postmenopausal women. First-line treatment of advanced, hormone-dependent breast cancer in postmenopausal women. Treatment of advanced breast cancer in women after natural menopause or artificially induced, previously treated with anti-estrogen drugs that have a recurrence or progression of cancer. 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. Letrozole has not been shown to be effective in patients with breast cancer without hormone receptors.
An anticancer drug - a non-steroidal aromatase inhibitor - an enzyme that converts adrenal androgens to oestrone and estradiol. Selective inhibition of aromatase causes the inhibition of estrogen biosynthesis in peripheral tissues and in tumor tissue. Letrozole inactivates aromatase by competitively associating with the cytochrome P450 heme aromatase, leading to the reduction of estrogen biosynthesis in all tissues in which it is present. In postmenopausal women with advanced breast cancer treated with a daily dose of 0.1-5 mg, letrozole reduces the estradiol, oestrone and oestrone sulphate concentration in the blood by 75-95% in all treated patients in relation to baseline values. Letrozole is highly specific in inhibiting aromatase activity, therefore, there is no need for adjuvant treatment with glucocorticosteroids or mineralocorticoids. After oral administration, letrozole is rapidly and completely absorbed from the gastrointestinal tract (bioavailability is 99.9%). The presence of food slightly reduces the rate of absorption of the drug, but has no effect on bioavailability. The drug is associated with plasma proteins in approximately 60%. The main route of letrozole metabolism is the reduction to the pharmacologically inactive metabolite - carbinol, which is carried out with the participation of the 3A4 and 2A6 cytochrome P450 isoenzymes. It is excreted mainly in the urine (approximately 90%), where 6% of the drug was administered unchanged and 75% as a metabolite. The remaining part is excreted in the faeces (about 3.8%). T0,5 is about 2 days.
Contraindications:
Hypersensitivity to letrozole or to any of the excipients. Endocrinological condition before menopause. Pregnancy. Breast-feeding.
Precautions:
For patients who are not known for their postmenopausal status, the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and / or estradiol should be determined before starting treatment. Only post-menopausal women can receive the medicine. The use of letrozole in a sufficient number of patients with a creatinine clearance less than 10 ml / min has not been studied; Before administering the drug, the potential risk-benefit ratio should be carefully considered in these patients. Treatment should be closely monitored in patients with severe hepatic impairment (Child-Pugh C), due to the increased concentration of the drug in the blood and the slower elimination of letrozole from the body. Patients with a history of osteoporosis and / or fracture or who are at increased risk of osteoporosis should have densitometric bone density tests before commencement of adjuvant or prolonged adjuvant therapy and should be monitored during and after letrozole treatment. treatment. If appropriate, treatment or prevention of osteoporosis should be instituted and carefully monitored. The drug contains lactose - should not be used in patients with rare hereditary problems of galactose intolerance, serious lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
Letrozole is contraindicated during pregnancy and breastfeeding.Letrozole should only be used in women who have been clearly confirmed to be after menopause. Due to reports about the resumption of ovarian function in patients during treatment with Letrozole, despite the explicitly stated post-menopausal condition at the time of starting therapy, the doctor should discuss appropriate methods of contraception with the patient when necessary.
Side effects:
Very common: hypercholesterolemia, hot flushes, increased sweating, joint pain, tiredness (including weakness, unwellness). Common: anorexia, increased appetite, depression, headache, dizziness, hypertension, nausea, indigestion, constipation, abdominal pain, diarrhea, vomiting, alopecia, rash (including erythematous, maculopapular, psoriasis and vesicular), dry skin , muscle pain, bone pain (reported only in the treatment of metastatic tumors), osteoporosis, bone fractures, vaginal bleeding, peripheral edema, weight gain. Uncommon: urinary tract infections, cancer pain (reported only in the treatment of metastatic tumors), leukopenia, anxiety (including nervousness), irritability, drowsiness, insomnia, memory disorders, sensory disturbances (including paraesthesia, hypoaesthesia), taste disorders , cerebrovascular accident, cataracts, eye irritation, blurred vision, palpitations (only in the treatment of metastatic cancers), tachycardia, ischemic events (including new cases or exacerbation of existing angina, angina requiring intervention, myocardial infarction and myocardial ischemia), thrombophlebitis (including superficial and deep vein thrombophlebitis), dyspnea, cough, dry mouth, oral mucositis (only for the treatment of metastatic tumors), increased liver enzymes, pruritus, urticaria, arthritis, frequent from urination, vaginal discharge, vaginal dryness, breast pain, generalized edema, dry mucous membranes, increased thirst, fever; weight loss. Rare: pulmonary embolism, arterial thrombosis, ischemic stroke. Not known: anaphylactic reactions, hepatitis, angioneurotic edema, toxic necrotic separation of the epidermis, erythema multiforme.
Dosage:
Orally. Adult and elderly patients: The recommended dose is 2.5 mg once a day. In patients with advanced breast cancer or metastatic breast cancer, treatment should be continued until a definitive progression of the cancer process. In the case of adjuvant and prolonged adjuvant treatment, the preparation should be continued for 5 years or until tumor recurrence, whichever comes first. In adjuvant therapy, the use of a sequential 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 4-8 months to achieve optimal tumor reduction. If the response to the treatment is insufficient, discontinue the preparation and set the date of surgery and (or) discuss with the patient further treatment options.Special groups of patients. It is not recommended for use in children and adolescents. In patients with renal insufficiency with creatinine clearance ≥10 ml / min, no dose adjustment is necessary. There is insufficient data on patients with renal failure whose creatinine clearance is less than 10 ml / min. Patients with mild to moderate hepatic impairment (Child-Pugh A or B) do not need to adjust their dose. There is insufficient data on patients with severe hepatic impairment. Patients with severe hepatic impairment (Child-Pugh C) require close supervision.Method of administration. The drug should be taken with or without food.
(C)
