Blocks the synthesis of estrogens in peripheral and in tumor tissues. In postmenopausal women, estrogens are mainly formed by the enzyme aromatase, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. Daily treatment with letrozole leads to lower concentrations of estradiol, estrone and estrone sulfate in plasma at 75-95% of the initial content. Violation of the synthesis of steroid hormones in the adrenal gland is not observed. The suppression of the synthesis of estrogen is maintained throughout the treatment. The blockade of estrogen biosynthesis does not lead to the accumulation of androgens are precursors of estrogens. Patients treated with letrozole, there were no changes in the concentrations of LH and follicle-stimulating hormone in the blood plasma, and there were no changes in thyroid function.
The pharmacokinetics of
Letrozole is rapidly and completely absorbed from testosterone suspension the gastrointestinal tract (GIT), the mean bioavailability of 99.9%. Food slightly decreases the rate of absorption, but the clinical significance of this has, therefore letrozole may be taken regardless of meals.
Contact letrozole to plasma proteins is approximately 60% (mainly albumin – 55%). The equilibrium concentration is reached within 2-6 weeks of daily administration of a daily dose of 2.5 mg. Pharmacokinetics is not linear.
Cumulation of long-term use are not observed.
Letrozole is largely metabolized by the action of CYP2A6 and CYP3A4 isoenzymes of cytochrome P450 to form a pharmacologically inactive carbinol compounds.
Write mainly kidneys as metabolites, to a lesser extent – through the intestines. The final half-life (T ½ ) is 48 hours.
Report from the plasma by hemodialysis.
The pharmacokinetic parameters of letrozole does not depend on the age of the patient.
The pharmacokinetic parameters are not changed in renal insufficiency.
In patients with moderate hepatic dysfunction (Child-Pugh B), the mean AUC values at and up to 37%, but remain within the range of values that have been reported in individuals without liver dysfunction. In patients with liver cirrhosis and severe impairment of its function (Child-Pugh C) AUC increased by 95% and the T ½ to 187%. However, given the good tolerability of high doses (5-10 mg / day) in these cases need not to change the dose of letrozole.
- Common forms of hormone-dependent breast cancer in postmenopausal women (with natural or artificially induced).
- Hypersensitivity to letrozole or to any other component of the drug.
- Endocrine status characteristic premenopauznom period.
- Pregnancy, lactation.
- Age up to 18 years.
Precautions : when expressed violations of liver and kidney function (creatinine clearance less than 10 ml / min). Before prescribing letrozole should be carefully weigh the relationship between the potential risk and the expected effect of treatment.
Dosing and Administration
Inside, regardless of meals.
The recommended dose of letrozole is 2.5 mg once a day, every day, for a long time.
If signs of disease progression receiving letrozole should be discontinued.
In elderly patients letrozole dose adjustment is required. Patients with impaired liver and / or kidney disease. In testosterone suspension patients with impaired hepatic or renal function (creatinine clearance > 10 ml / min) dose adjustment is required. However, patients with severe hepatic impairment should be under constant supervision.
The frequency of side effects: very common – > 10%, often – > 1-10%, sometimes – > 0.1% – <1%, rarely – > 0.01-0.1%, rarely – <0.01%, including isolated reports . On the part of the digestive system : often -toshnota, vomiting, anorexia, dyspepsia, constipation, diarrhea; sometimes – pain in the abdominal area, stomatitis, dry mouth, increased activity of “liver” enzymes. On the part of the central and peripheral nervous system : often – headache, dizziness, weakness; sometimes – depression, anxiety, drowsiness, insomnia, memory impairment, dysesthesia; rarely – irritability, nervousness, hyperesthesia, hypoesthesia. From the hematopoietic system and lymphatic system : sometimes -leykopeniya. On the part of the cardiovascular system : sometimes – palpitations, tachycardia, thrombophlebitis, increased blood pressure (BP); rarely – pulmonary embolism, arterial thrombosis, cerebrovascular accident. Respiratory system : sometimes – shortness of breath. Skin and skin appendages: common – alopecia, increased sweating, skin rash; sometimes – itching, dry skin, urticaria. From the musculoskeletal system : often – myalgia, arthralgia, ossalgia arthritis. From the senses : sometimes – cataract, eye irritation, “blurred” vision, taste disturbance. On the side urinary system : rarely – urinary frequency. reproductive system : sometimes – vaginal bleeding, vaginal discharge, vaginal dryness. Other : very often – hot flashes ( “hot flushes”), often -Increased fatigue, asthenia, malaise, peripheral edema, weight gain; sometimes – hypercholesterolemia, generalized edema, pain at tumor sites, urinary tract infection; rarely – fever, thirst, weight loss.
Specific treatment of overdose is unknown. Symptomatic and supportive therapy.
Interaction with other drugs
of clinical experience on the use of letrozole in combination with other anticancer drugs are not available at the moment.
According to the results of studies in vitro, , letrozole inhibits the activity of cytochrome P450 isoenzymes – CYP2A6 and CYP2C19 (last – in moderation). In deciding on the significance of these data for the clinic, please note that isoenzyme CYP2A6 does not play a significant role in the metabolism of drugs. Experiments in vitro showed that letrozole in concentrations 100 times the equilibrium value of plasma has no ability to significantly inhibit the metabolism of diazepam (substrate for CYP2C19). Thus, clinically relevant interactions with CYP2C19 isoenzyme are unlikely. However, 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.
Patients with severely impaired liver function should be under constant supervision.
Some side effects of the drug, such as testosterone suspension general weakness and dizziness, may affect the ability to perform potentially hazardous activities that require concentration and fast reactions. In this regard, care must be taken in the management of vehicles and mechanisms. buy anabolic steroids online bruce lee’s workout anabolic steroids online uk