Supplementary treatment in postmenopausal women with invasive early-stage breast cancer, with the presence of hormone receptors. Prolonged adjuvant treatment of hormone-dependent invasive breast cancer in postmenopausal women who had previously received standard adjuvant Tamoxifen therapy for 5 years. First-line treatment in postmenopausal women with advanced, hormone-dependent breast cancer. Advanced breast cancer in women after natural or artificial menopause, previously treated with antiestrogens who have relapsed or progressed. Neoadjuvant treatment in postmenopausal women with HER2-negative breast cancer with the presence of hormone receptors that are not eligible for chemotherapy and in whom there is no indication for immediate surgery. The drug has not been shown to be effective in patients with hormone receptor negative breast cancer.
Anticancer drug - a non-steroidal aromatase inhibitor - an enzyme that transforms adrenal androgens, primarily androstenedione and testosterone, into estrone 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 bound to plasma proteins in about 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 remainder is excreted in the faeces (approximately 3.8%). T0,5 is about 2 days.
Contraindications:
Hypersensitivity to letrozole or other ingredients of the preparation. Women before menopause. Pregnancy and breastfeeding.
Precautions:
For patients who are unsure whether they are after menopause, LH, FSH and / or estradiol should be determined before treatment is started. Only postmenopausal women can be treated with the preparation. The preparation has not been studied in a sufficient number of people with a creatinine clearance <10 ml / min. Before using the preparation in such patients, the potential risks and benefits of treatment should be carefully considered. In people with severe hepatic impairment (Child-Pugh grade C) systemic exposure and T0,5 in the final phase of elimination they were about twice as large as in comparison to healthy volunteers. Therefore, such patients require strict control. Letrozole is a powerful drug that reduces estrogen levels. In women with an history of osteoporosis and / or bone fractures, or with an increased risk of osteoporosis before inclusion or extended adjuvant treatment, bone mineral density should be formally evaluated and continued control over time and after treatment with letrozole. If necessary, treatment or prevention of osteoporosis should be included and careful observation should be carried out. In adjuvant therapy, sequential treatment (letrozole for 2 years followed by tamoxifen for 3 years) may also be considered depending on the patient's safety profile. Co-administration with Tamoxifen, other antiestrogens or estrogen-containing medicines should be avoided.It is not recommended for use in children and adolescents. Due to the lactose content, the preparation should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
The preparation can be used only in women who have clearly been confirmed to undergo menopause. Due to the fact that there are reports of resumption of ovarian function during treatment with Letrozole, despite a clear post-menopausal condition at the beginning of therapy, if necessary, the physician should discuss with the patient appropriate methods of contraception. The preparation is contraindicated in pregnancy and breast-feeding. Fertility: the pharmacological effect of letrozole is to reduce estrogen production by inhibiting aromatase. In pre-menopausal women, the inhibition of estrogen synthesis leads via feedback to increased gonadotropin concentrations (LH, FSH). In turn, increased levels of FSH stimulate the growth of follicles and may induce ovulation.
Side effects:
Very common: hypercholesterolemia, increased sweating, painful joints, hot flushes, fatigue (including weakness, unwellness). Common: lack of appetite, increased appetite, depression, headache and dizziness, hypertension, nausea, vomiting, indigestion (only in patients with metastases), constipation, abdominal pain, diarrhea, alopecia, rash (including erythematous rash, maculopapular rash, psoriasis and follicular), dry skin, muscle pain, bone pain (only in patients with metastases), osteoporosis, bone fractures, genital tract bleeding, peripheral edema, weight gain. Uncommon: urinary tract infections, tumor pain (only in patients with metastases), leukopenia, generalized edema, anxiety (including nervousness), irritability, drowsiness, insomnia, memory problems, sensory disturbances (including paresthesia and weakness of sensation), taste, cerebrovascular events, cataracts, eye irritation, blurred vision, palpitations (only in patients with metastases), tachycardia, cardiac ischemia (emergence of new or exacerbation of existing angina, angina requiring surgical treatment, myocardial infarction and ischemia myocarditis), thrombophlebitis (including superficial and deep vein thrombophlebitis), dyspnea, cough, oral mucositis (only in patients with metastases), dry mouth, increased liver enzymes, pruritus, urticaria, joints, more frequent urination, vaginal discharge, dryness hwy, breast pain, fever, dry mucous membranes, increased thirst, weight loss. Rare: pulmonary embolism, arterial thrombosis, ischemic stroke. Not known: anaphylactic reaction, hepatitis, angioneurotic edema, toxic epidermal necrolysis, erythema multiforme.
Dosage:
Orally. Adult patients, including the elderly: 2.5 mg once a day. In patients with advanced breast cancer or metastatic disease, letrozole should be continued until the cancer has progressed definitively. In the case of adjuvant or prolonged treatment, adjuvant therapy should be continued for 5 years or until tumor recurrence, whichever occurs first. In adjuvant therapy, a sequential therapy regimen (letrozole for 2 years followed by tamosifen for 3 years) may also be considered. In the neoadjuvant treatment, drug therapy can be continued for 4-8 months to achieve optimal tumor reduction. If the answer is insufficient, the treatment should be discontinued and the operation should be planned and / or other options should be discussed with the patient. No dose adjustment is required in patients with impaired renal function with a creatinine clearance ≥ 10 ml / min. Patients with mild or moderate hepatic impairment (Child-Pugh A or B grade) do not need to modify the dose. Data on patients with severe hepatic impairment (Child-Pugh C) are insufficient; these patients require close monitoring. The tablets can be taken with or without food.
(C)
