Loreta 2,5mg №30 pills
Letrozole has an antiestrogenic effect, selectively inhibits aromatase (an estrogen synthesis enzyme) by highly specific competitive binding to the subunit of this enzyme, the heme of cytochrome P450. Blocks the synthesis of estrogen in both peripheral and tumor tissues.
In postmenopausal women, estrogens are formed mainly with the participation of the aromatase enzyme, which converts androgens (primarily androstenedione and testosterone) synthesized in the adrenal glands into estrone and estradiol.
Daily intake of letrozole in a daily dose of 0.1-5 mg leads to a decrease in the concentration of estradiol, estrone and estrone sulfate in the blood plasma by 75-95% of the initial content. Estrogen synthesis supreyassion is maintained throughout the entire treatment period.
When using letrozole in the dose range from 0.1 to 5 mg, there is no violation of the synthesis of steroid hormones in the adrenal glands, the test with ACTH does not reveal any abnormalities in the synthesis of aldosterone or cortisol. Additional administration of glucocorticoids and mineralocorticoids is not required.
The blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are precursors of estrogen. No changes in luteinizing and follicle-stimulating hormones in the blood plasma, changes in thyroid function, changes in the lipid profile, an increase in the frequency of myocardial infarction and stroke were observed during the administration of letrozole.
The treatment of letrozole slightly increases the frequency of osteoporosis (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 of the same age.
Adjuvant therapy with letrozole in early stages of breast cancer reduces the risk of recurrence, increases survival without signs of disease for 5 years, reduces the risk of developing secondary tumors.
Prolonged adjuvant therapy with letrozole reduces the risk of relapse by 42%. A significant survival benefit without signs of disease in the letrozole group was noted regardless of the involvement of lymph nodes. Letrozole treatment reduces mortality in patients with lymph node involvement by 40%.
PharmacokineticsLetrozole is rapidly and completely absorbed from the gastrointestinal tract of the gastrointestinal tract, the average bioavailability is 99.9%. Food intake slightly reduces the rate of absorption. Average time Tmax is 1 hour when taking letrozole on an empty stomach and 2 hours when taken with food; mean Cmax is (129 &№177; 20.3) nmol / l when taken on an empty stomach and (98.7 &№177; 18.6) nmol / l - when taken with food, but the degree of absorption of letrozole (assessed by AUC value) does not change.
Small changes in the rate of absorption are regarded as having no clinical significance, therefore letrozole can be taken regardless of the meal. The connection of letrozole with plasma proteins is approximately 60% (mainly with albumin - 55%). The concentration of letrozole in erythrocytes is about 80% of that in plasma. The apparent volume of distribution in the equilibrium state is about (1.87 &№177; 0.47) l / kg. Equilibrium concentration is achieved within 2-6 weeks of daily intake of a daily dose of 2.5 mg. Pharmacokinetics is nonlinear. Cumulation with prolonged use is not marked. Letrozole is largely metabolized by the CYP3A4 and CYP2A6 isoenzymes of cytochrome P450 to form a pharmacologically inactive carbinol compound.
Excreted mainly by the kidneys in the form of metabolites, to a lesser extent - through the intestines. Final t1/2 48 hours. The pharmacokinetic parameters of letrozole do not depend on the age of the patient. In renal failure, the pharmacokinetic parameters do not change. In moderately severe liver dysfunction (Child-Pugh B), the average AUC values, although higher by 37%, remain within the range of values observed in individuals without liver dysfunction. In patients with cirrhosis of the liver and severely impaired function (Child-Pugh C), the AUC is increased by 95% and T1/2 - by 187%. However, given the high tolerability of high doses of the drug (5-10 mg / day), in these cases there is no need to change the dose of letrozole.
- The early stages of breast cancer, whose cells have hormone receptors, in postmenopausal women as an adjuvant therapy.
- Early stages of breast cancer in postmenopausal women after the completion of standard adjuvant therapy with tamoxifen as extended adjuvant therapy.
- Common hormone-dependent forms of breast cancer in postmenopausal women (first line therapy).
- Common forms of breast cancer in postmenopausal women (natural or artificially induced) who received prior anti-estrogen therapy.
- Hypersensitivity to lethrose or any other component of the drug; endocrine status characteristic of the reproductive period;
- pregnancy; breastfeeding period;
- children's age (efficacy and safety for children has not been established).
Carefully:There is no data on the use of letrozole in patients with creatinine clearance less than 10 ml / min. Before prescribing letrozole, such patients should carefully weigh the ratio between the potential risk and the expected effect of treatment.
Dosage and administrationInside, regardless of the meal.
Adults recommended dose of LORETA is 2.5 mg 1 time per day, daily, long-term.
As an extended adjuvant therapy, treatment should continue for 5 years (not longer).
If there is evidence of disease progression, LORETA should be discontinued.
Elderly patients do not require dose adjustment for LORETA. Patients with impaired liver and / or kidney function: in case of impaired liver function or kidney function (creatinine clearance> 10 ml / min), dose adjustment is not required. However, for severely impaired liver function (according to the Child-Pugh C scale), patients should be monitored continuously.
Side effectAs a rule, adverse reactions were mild or moderate and were mainly associated with the suppression of estrogen synthesis.
The incidence of adverse reactions is estimated as follows: occurring very often - ˃10%, often - 1-10%, sometimes - 0.1-1%, rarely - 0.01-0.1%, very rarely - ˂0.01 %, including individual messages.
On the part of the digestive system: often - nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes - abdominal pain, stomatitis, dry mouth, increased activity of liver enzymes; very rarely - hepatitis.
On the part of the nervous system: often - headache, dizziness, depression; sometimes - anxiety, nervousness, irritability, drowsiness, insomnia, memory impairment, dysesthesia, paresthesia, hypoesthesia, disturbed taste perception, episodes of cerebral circulation.
From the side of blood-forming organs: sometimes - leukopenia.
Since the cardiovascular system: sometimes - a feeling of heartbeat, tachycardia, thrombophlebitis of the superficial and deep veins, increased blood pressure, coronary heart disease (angina, myocardial infarction, heart failure), thromboembolism; rarely - pulmonary embolism, arterial thrombosis, stroke.
On the part of the respiratory system: sometimes - shortness of breath, cough.
From the side of skin and skin appendages: often - alopecia, excessive sweating, skin rash (including erythematous, maculopapular, vesicular rash, psoriasis-like rash); sometimes - itching, dry skin, urticaria; very rarely - angioedema, anaphylactic reactions, Lyell's syndrome (toxic epidermal necrolysis), Stephen-Johnson syndrome (erythema multiforme).
From the musculoskeletal system: very often - arthralgia; often - myalgia, bone pain, osteoporosis, bone fractures; sometimes - arthritis.
On the part of the senses: sometimes - cataract, irritation of the eyes, blurred vision, impaired taste.
On the part of the urinary system: sometimes - frequent urination, infections of the urinary tract.
Reproductive system: sometimes - vaginal bleeding, vaginal discharge, vaginal dryness, pain in the mammary glands.
Other: very often - hot flashes (hot flashes); often - increased fatigue, asthenia, malaise, peripheral edema, weight gain, hypercholesterolemia, anorexia, increased appetite; sometimes - weight loss, thirst, hyperthermia (pyrexia), dry mucous membranes, generalized edema, pain in tumor foci.
OverdoseSymptoms: There are separate reports of overdose of letrozole.
Treatment: symptomatic and supportive therapy. Any specific treatment for overdose is unknown. Letrozole is excreted from the plasma through hemodialysis.
Interaction with other drugsWith the simultaneous appointment of letrozole with cimetidine and warfarin, there are no clinically significant interactions.
Clinical experience on the use of letrozole in combination with other anticancer agents is currently not available.
According to the results of an in vitro study, letrozole suppresses the activity of cytochrome P450 isoenzymes - CYP2A6 and CYP2C19 (the latter is moderate). When deciding on the significance of this data for the clinic, it is necessary to take into account that the CYP2A6 isoenzyme does not play a significant role in the metabolism of drugs. In in vitro experiments, it was shown that letrozole in concentrations 100 times higher than the equilibrium values in plasma does not have the ability to significantly suppress the metabolism of diazepam (a substrate for CYP2C19). Thus, clinically significant interactions with the CYP2C19 isoenzyme are unlikely. However, caution should be exercised in the combined use of letrozole and drugs that are metabolized mainly with the participation of the above isoenzymes and have a narrow therapeutic index.
Patients with severely impaired liver function should be under constant supervision.
During therapy with letrozole, given the potential for pregnancy, women in the perimenopausal and early postmenopausal periods should use reliable methods of contraception until a stable postmenopausal hormone level is established.
Influence on ability to driving of the car and control of mechanisms. Some side effects of the drug, such as general weakness and dizziness, can affect the ability to perform potentially hazardous activities that require concentration and quick reactions. In this regard, care should be taken when driving vehicles and machinery.
Release formpills, film coated 2.5 mg. On 10 pills in blisters from polyamide / aluminum foil / PVC // aluminum foil. 3 or 9 blisters packed together with instructions for use in a cardboard box.
Storage conditionsAt a temperature not higher than 25aboutWITH.
Keep out of the reach of children.
3 years. Do not use after the expiration date printed on the package.
It is a drug. Consultation with a doctor is required.