Supplementary treatment in postmenopausal women with early-stage breast cancer with the presence of hormone receptors. Prolonged adjuvant therapy in the early stage of hormone-dependent breast cancer in postmenopausal women who have previously received standard adjuvant Tamoxifen therapy for 5 years. First-line treatment in postmenopausal women with advanced, hormone-dependent breast cancer. Treatment of advanced breast cancer in postmenopausal or artificially induced menopausals, previously treated with anti-estrogen drugs that have relapsed or progressed to cancer. The drug has not been shown to be effective in patients with hormone receptor negative breast cancer.
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 the treatment of tumors, where the proliferation of tumor tissue depends on the presence of estrogens and endocrine therapy 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 women, daily doses of letrozole 0.1-5 mg do not cause changes in cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone and ACTH in the blood, plasma renin activity, LH and FSH levels, or thyroid function. After oral administration, letrozole is rapidly and completely absorbed from the gastrointestinal tract (mean absolute bioavailability is 99.9%). Food slightly reduces the rate of absorption of the drug (median tmax: 1 h on an empty stomach compared to 2 h after a meal), but does not affect the degree of absorption. The drug is bound to plasma proteins in about 60%. It is quickly and extensively distributed to tissues. The main route of letrozole metabolism is the reduction to the pharmacologically inactive metabolite - carbinol, which is mediated by the CYP3A4 and CYP2A6 isoenzymes. The drug is mainly excreted in the urine as a metabolite, in a small amount with faeces. T0,5 is about 2 days. The steady state drug concentrations remain constant, there is no accumulation of letrozole.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Endocrinological condition before menopause. Pregnancy and breastfeeding.
Precautions:
In patients with a post-menopausal condition not explained, the levels of LH, FSH and / or estradiol should be determined before the treatment with letrozole to clearly determine the menopausal state in which the patient is. Particularly with caution (after careful consideration of the benefit-risk ratio), patients with creatinine clearance <10 ml / min or severe hepatic impairment (hepatic cirrhosis, C according to Child-Pugh) should be used. Patients with a history of osteoporosis and / or a history of high risk osteoporosis should have bone densitometry performed prior to initiating adjuvant treatment or prolongation of adjuvant therapy and should be monitored for osteoporosis during and after treatment. If there are indications, treatment or prevention of osteoporosis should be started and regular monitoring of the effectiveness of these activities. 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:
Letrozole is contraindicated in pregnancy and breast-feeding. In women who could become pregnant (during the perimenopausal or early post-menopausal period), a pregnancy test should be performed and appropriate contraception should be used prior to the initiation of treatment until the post-menopausal state is confirmed.
Side effects:
Very common: increased sweating, joint pain, hot flushes, fatigue, weakness.Common: lack of appetite, increased appetite, hypercholesterolemia, depression, headache, dizziness, nausea, vomiting, indigestion, constipation, diarrhea, alopecia, rash (including erythematous rash, maculopapular, psoriasis and vesicular), muscle pain, bone pain , osteoporosis, bone fractures, malaise, peripheral edema, weight gain. Uncommon: urinary tract infections, cancer pain (not applicable to adjuvant treatment and prolonged adjuvant treatment), leukopenia, generalized edema, anxiety, nervousness, irritability, drowsiness, insomnia, memory impairment, sensory disturbances (including paraesthesia and hypoaesthesia), taste disorders , cerebrovascular accident, cataracts, eye irritation, blurred vision, palpitations, tachycardia, thrombophlebitis (including thrombophlebitis of superficial and deep veins), hypertension, ischemic cardiac events, dyspnea, cough, abdominal pain, stomatitis oral, dry mouth, increased liver enzymes, pruritus, dry skin, urticaria, arthritis, frequent urination, bleeding from the genital tract, vaginal discharge, vaginal dryness, breast pain, fever, dry mucous membranes, increased thirst, weight loss body. Rare: pulmonary embolism, arterial thrombosis, cerebral infarction.
Dosage:
Orally. Adult (also elderly) patients: 2.5 mg once a day. In adjuvant therapy, treatment should be continued for 5 years or until tumor disease returns. In adjuvant treatment, the clinical experience is 2 years (median duration of treatment was 25 months). In extended adjuvant treatment, the clinical experience is 4 years (median duration of treatment). In patients with advanced cancer or metastatic cancer, letrozole should be continued until the tumor progresses markedly.Special groups of patients. No dosage adjustment is necessary for patients with impaired renal function with CCr> 30 ml / min. There is insufficient data on patients with CCr <30 ml / min and patients with severe hepatic impairment.
(C)
