In post-menopausal women, estrogens are mainly formed by the enzyme aromatase, which converts adrenal androgens (primarily, testosterone and androstenedione) to estrone and estradiol. Daily priemletrozola a daily dose of 0.1-5 mg reduces testosterone suspension side effects concentrations of estradiol, estrone and estrone sulfate in plasma at 75-95% of the initial content. Suppression of estrogen synthesis is maintained throughout the treatment period.
When using letrozole in a dosage range of from 0.1 to 5 mg disorders synthesis of steroid hormones in the adrenal gland is not observed, the test does not detect ACTH synthesis of aldosterone or cortisol disorders. Additional destination glucocorticoid and mineralocorticoid is required.
Estrogen biosynthesis does not lead to the blockade of androgen accumulation, which are precursors of estrogens. In patients receiving letrozole changes in concentrations of luteinizing and follicle-stimulating hormone in blood plasma, changes in thyroid function, lipid profile changes, increasing the frequency of myocardial infarction and stroke have been reported.
The treatment with letrozole increased slightly osteoporosis rate (6.9% compared with 5 5% for placebo). However, the frequency of bone fractures in patients receiving letrozole does not differ from that in healthy people the same age.
Adjuvant terapiya.letrozolom early breast cancer reduces the risk of relapse increases disease-free survival at 5 years, reduces the risk of secondary tumors.
Extended adjuvant letrozole therapy reduces the risk of relapse by 42%. Significant advantage in disease-free survival in the group letrozole noted regardless of the involvement of lymph nodes. Letrozole treatment reduces mortality of patients with lymph node involvement by 40%.
- Early stage breast cancer whose cells have receptors for the hormones in postmenopausal women, as adjuvant therapy.
- Early stage breast cancer in postmenopausal women after completing standard adjuvant tamoxifen therapy of cancer as extended adjuvant therapy.
- Common forms of hormone-dependent breast cancer in postmenopausal women (first line therapy).
- Common forms of breast cancer in postmenopausal women (with natural or artificially induced), previously treated antiestrogens.Contraindications
- Hypersensitivity to the active substance or to any excipient the formulation;
- endocrine status, characteristic of reproductive age;
- pregnancy, lactation;
- Children up to age 18 years (effectiveness and safety have not been established for children).Precautions
Severe hepatic (class C Child-Pugh), and renal insufficiency (creatinine clearance (CC) of less than 10 ml / min), lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Application of pregnancy and breastfeeding period of
preparation Lestrodeks contraindicated during pregnancy and. lactation.
During therapy with Lestrodeks, given the potential for pregnancy, women in the perimenopausal and early postmenopausal period should use reliable methods of contraception until a stable post-menopausal hormone levels.
Dosing and Administration
Inside, regardless of meals.
The recommended dose of the drug Lestrodeks -. 2.5 mg 1 time per day
as extended adjuvant therapy, treatment should continue for 5 years or until evidence of disease progression.
In patients with advanced or metastatic cancer treatment drug Lestrodeks should be continued until the apparent tumor progression.
You do not need dose adjustment for elderly patients.
patients with hepatic impairment and / or renal impairment: the human liver or renal function (creatinine clearance greater than 10 mL / min) correction dose is not required. Insufficient data when using the drug in patients with CC less than 10 ml / min or patients with severely impaired hepatic function (class C Child-Pugh) (see Precautions for use and Pharmacokinetics) . When therapy with Lestrodeks this group of patients require constant monitoring of their condition.
Generally, adverse events were mild or moderately expressed and, mainly related to the suppression of the synthesis of oestrogens (such as “hot flashes” Blood-to-face, alopecia and vaginal bleeding).
The incidence of adverse reactions is as follows: Very often (≥ 1/10), often (≥ 1/100, <1/10), sometimes (≥ 1/1000, <1/100), rarely (≥ 1/10000, <1/1000), very rare (<1 / 10000), the frequency is not known .Infectious and parasitic diseases sometimes – urinary tract infection. Benign, malignant and unspecified tumors (including cysts and polyps) sometimes – pain in the tumor foci (not applicable when the adjuvant and extended adjuvant setting). blood disorders and lymphatic system sometimes – leukopenia. Violations of the metabolism and nutrition often – anorexia, appetite increase, hypercholesterolaemia,sometimes – generalized edema. Violations of the psyche often – depression, sometimes – anxiety, including anxiety and irritability. Disorders of the nervous system often – headache, dizziness, andsometimes – drowsiness, insomnia, memory impairment; sensitivity disorder (dysesthesia), including paresthesia; hypoesthesia, taste disturbance, episodes of cerebrovascular accidents. Violations of the organ of vision Sometimes – cataract, eye irritation, fuzzy vision; Disorders of the heart Sometimes – palpitations, tachycardia. Violations of the vessels sometimes – thrombophlebitis, including thrombophlebitis of superficial and deep venous, arterial hypertension, coronary heart disease, rare . – pulmonary embolism, arterial thrombosis, stroke, Disorders of the respiratory system, the chest and mediastinum sometimes – shortness of breath, cough. Violations of the gastrointestinal tract often – nausea, vomiting, dyspepsia , constipation, testosterone suspension side effects diarrhea, sometimes – abdominal pain, stomatitis, dry mouth.Violations of the liver and bile ducts sometimes – increased activity of “liver” enzymes. Violations of the skin and subcutaneous tissue Very often – sweating; often – alopecia; rash, including erythematous, maculopapular, vesicular rash; psoriasiform rash, sometimes – itching, dry skin, urticaria, the frequency is not known – angioedema, anaphylactic reactions. Violations of the musculoskeletal and connective tissue Very often – arthralgia; often – myalgia, bone pain, osteoporosis, bone fractures, sometimes – arthritis. violations of the kidney and urinary tract sometimes – frequent urination. violation by the genitals and breast Sometimes – vaginal bleeding, vaginal discharge, vaginal dryness, breast pain. General disorders and at the injection site is often – “tides” of blood, fatigue including asthenia, often – malaise, peripheral edema, sometimes – hyperthermia, mucosal dryness, thirst. The impact on the results of laboratory and instrumental studies often – weight gain, sometimes – loss of weight.
There are some reports of letrozole overdose. Treatment : any specific treatment of overdose is not known. Symptomatic and supportive therapy. Letrozole is derived from the plasma by hemodialysis.
Interaction with other drugs
When concomitant administration testosterone suspension side effects of letrozole with cimetidine and warfarin clinically significant interactions are observed. Clinical experience in the use of letrozole in combination with other anticancer agents has not at this time.
According to studies in vitro , letrozole inhibits the activity of cytochrome P450 isozymes CYP2A6 and moderately – CYP2C19. Caution should be exercised when used together letrozole and drugs metabolized mainly with the participation of the aforementioned isoenzymes and having a narrow therapeutic index.
Precautions for the use
Patients who do not have clear postmenopausal status, before the start of treatment is recommended to determine the concentration of LH, FSH and / or estradiol to confirm menopausal status. Renal impairment There is no sufficient data the use of letrozole in patients with CC patients less than 10 ml / min. In patients with CC less than 10 ml / min should weigh the potential risks and expected benefits.Liver dysfunction drug Lestrodeks should be used with caution, only after careful evaluation of the ratio of the potential benefits and potential risks in patients with severely impaired hepatic function (class C on a scale Child-Pugh) (see section pharmacokinetics ). The effect on bone Letrozole much effect on reducing the concentration of estrogen. In patients with osteoporosis and / or fractures in the history of the disease or at increased risk of osteoporosis, bone mineral density should be assessed by DXA at baseline and regularly along its length. If necessary, prescribe treatment or prevention of osteoporosis and carefully monitor the patient’s condition (see section Adverse effects). Other precautions Since each tablet coated membrane shell Lestrodeks formulation contains 58.4 mg of lactose as lactose monohydrate, it is not recommended for patients with rare hereditary disorders of galactose intolerance, severe lactase deficiency with or glucose-galactose malabsorption.
Running low dose t3 clen cycle trying to lose bodyfat isn’t a real hot idea imo.