Loreta pills 2.5mg, 30pcs

Composition

Film-coated tablets 2.5 mg.

 10 tablets in blisters made of polyamide / aluminum foil / PVC//aluminum foil.

3 or 9 blisters are packed together with the instructions for use in a cardboard box.

Pharmacological action

Pharmacodynamics

Letrozole has an anti-estrogenic effect, selectively inhibits aromatase (an enzyme of estrogen synthesis) by highly specific competitive binding to the subunit of this enzyme, the cytochrome P 450 heme. It blocks the synthesis of estrogens in both peripheral and tumor tissues.

In postmenopausal women, estrogens are formed mainly with the participation of the aromatase enzyme, which converts androgens synthesized in the adrenal glands (primarily androstenedione and testosterone) 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 blood plasma by 75-95% of the initial content. Suppression of estrogen synthesis 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 ACTH test does not detect violations of the synthesis of aldosterone or cortisol. Additional use of glucocorticoids and mineralocorticoids is not required.

The blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are precursors of estrogens. While taking letrozole, there were no changes in the concentrations of luteinizing and follicle-stimulating hormones in blood plasma, changes in thyroid function, changes in the lipid profile, and an increase in the frequency of myocardial infarction and stroke.

The incidence of osteoporosis is slightly increased during treatment with letrozole (6.9% compared to 5.5% on placebo). However, the incidence of bone fractures in patients receiving letrozole does not differ from that in healthy people of the same age.

Adjuvant therapy with letrozole for early-stage breast cancer reduces the risk of relapses, increases the survival rate without signs of the disease for 5 years, and reduces the risk of developing secondary tumors.

Prolonged adjuvant therapy with letrozole reduces the risk of relapse by 42%.

A significant advantage in disease-free survival in the letrozole group was observed regardless of the involvement of lymph nodes. Treatment with letrozole reduces the mortality of patients with lymph node involvement by 40%.

Pharmacokinetics

Letrozole is rapidly and completely absorbed from the gastrointestinal tract, with an average bioavailability of 99.9%. Food intake slightly reduces the rate of absorption. The average Tmax time is 1 hour when taking letrozole on an empty stomach and 2 hours when taking it with food; the average Cmax value is (129±20.3) nmol/l when taken on an empty stomach and (98.7±18.6) nmol/l when taken with food, but the degree of absorption of letrozole (when evaluated by AUC) does not change.

Small changes in the rate of absorption are considered to be of no clinical significance, so letrozole can be taken regardless of food intake. The association of letrozole with plasma proteins is approximately 60% (mainly with albumin-55%). The concentration of letrozole in red blood cells is about 80% of that in the blood plasma. The apparent volume of distribution at steady state is about (1.87±0.47) l / kg. Steady-state concentration is reached during 2-6 weeks of daily use of a daily dose of 2.5 mg

. Pharmacokinetics are non-linear. Accumulation with prolonged use was not observed. Letrozole is largely metabolized by cytochrome P450 isoenzymes CYP3A4 and CYP2A6 to form a pharmacologically inactive carbinol compound.

It is mainly excreted by the kidneys in the form of metabolites, to a lesser extent-through the intestines. The final T 1/2 is 48 h. The pharmacokinetic parameters of letrozole do not depend on the patient’s age. In patients with renal insufficiency, the pharmacokinetic parameters do not change. With moderate hepatic impairment (Child-Pugh B), the average AUC values, although higher by 37%, remain within the range of values observed in individuals without impaired liver function.

In patients with cirrhosis of the liver and severe liver dysfunction (Child-Pugh C), AUC increases by 95% and T 1/2-by 187%. However, given the good tolerability of high doses of the drug (5-10 mg/day), in these cases there is no need to change the dose of letrozole.

Indications

Early-stage breast cancer, whose cells have hormone receptors, in postmenopausal women as adjuvant therapy.

Early-stage breast cancer in postmenopausal women after completion of standard adjuvant tamoxifen therapy 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 previous antiestrogen therapy.

Contraindications

Hypersensitivity to letrolose or any other component of the drug; endocrine status characteristic of the reproductive period;

pregnancy; breast-feeding period;

childhood (efficacy and safety for children has not been established).

With caution:  there are no data on the use of letrozole in patients with creatinine clearance less than 10 ml/min. Before prescribing letrozole to such patients, the ratio between the potential risk and the expected effect of treatment should be carefully weighed.

Side effects

As a rule, adverse reactions were mild or moderate and mainly associated with suppression of estrogen synthesis.

The frequency 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 reports.

From the digestive system:  often – nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes-abdominal pain, stomatitis, dry mouth, increased activity of liver enzymes; very rarely-hepatitis.

Nervous system disorders:  often – headache, dizziness, depression; sometimes-anxiety, nervousness, irritability, drowsiness, insomnia, memory loss, dysesthesia, paresthesia, hypesthesia, impaired taste perception, episodes of cerebral circulation disorders.

From the side of hematopoietic organs:  sometimes-leukopenia.

From the cardiovascular system:  sometimes-palpitation, tachycardia, superficial and deep vein thrombophlebitis, increased blood pressure, coronary heart disease (angina, myocardial infarction, heart failure), thromboembolism; rarely – pulmonary embolism, arterial thrombosis, stroke.

Respiratory system disorders:  sometimes-shortness of breath, cough.

From the side of the skin and skin appendages:  often – alopecia, excessive sweating, skin rash (including erythematous, maculopapular, vesicular rash, psoriasis-like rashes); sometimes-pruritus, dry skin, urticaria; very rarely-angioedema, anaphylactic reactions, Lyell’s syndrome (toxic epidermal necrolysis), Stephen-Johnson syndrome (erythema multiforme).

Musculoskeletal disorders:  very often – arthralgia; often-myalgia, bone pain, osteoporosis, bone fractures; sometimes-arthritis.

From the side of the senses:  sometimes-cataracts, eye irritation, blurred vision, impaired taste sensations.

From the urinary system:  sometimes-frequent urination, urinary tract infections.

From the side of the reproductive system:  sometimes-vaginal bleeding, vaginal discharge, vaginal dryness, pain in the mammary glands.

Other services:  very often-paroxysmal sensations of heat (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.

Interaction

No clinically significant interactions were observed when letrozole was co-administered with cimetidine and warfarin.

There is currently no clinical experience with the use of letrozole in combination with other antitumor agents.

According to the results of an in vitro study, letrozole suppresses the activity of cytochrome P 450 isoenzymes-CYP2A6 and CYP2C19 (the latter is moderate). When deciding on the significance of these data for the clinic, it should be taken into account that the CYP2A6 isoenzyme does not play a significant role in drug metabolism.

In vitro experiments have shown that letrozole at concentrations 100 times higher than steady-state plasma values does not significantly inhibit the metabolism of diazepam (a substrate for CYP2C19). Thus, clinically significant interactions with the CYP2C19 isoenzyme are unlikely. However, caution should be exercised when concomitantly using letrozole and drugs that are primarily metabolized with the participation of the above-mentioned isoenzymes and have a narrow therapeutic index.

How to take it, course of use and dosage

Inside, regardless of food intake.

For adults, the recommended dose of LORETA is 2.5 mg once a day, daily, for a long time.

As an extended adjuvant therapy, treatment should be continued for 5 years (no longer).

If there are signs of disease progression, LORETA should be discontinued.

In elderly patients, no dose adjustment of LORETA is required.

Patients with impaired liver and/or kidney function: in patients with impaired liver or kidney function (creatinine clearance >10 ml / min), no dose adjustment is required.

However, patients with severe hepatic impairment (Child-Pugh C score) should be constantly monitored.

Overdose

Symptoms: there are isolated reports of overdose of letrozole.

Treatment: symptomatic and supportive care. Any specific treatments for overdose are unknown.

Letrozole is eliminated from the plasma by hemodialysis.

Special instructions

Patients with severe hepatic impairment should be constantly monitored.

During therapy with letrozole, given the potential for pregnancy, women in the perimenopausal and early postmenopausal periods should use reliable methods of contraception until stable postmenopausal hormone levels are established.

Influence on the ability to drive a car and manage mechanisms. Some side effects of the drug, such as general weakness and dizziness, may affect the ability to perform potentially dangerous activities that require concentration and rapid reactions. In this regard, care should be taken when driving vehicles and mechanisms.

Active ingredient

Letrozole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Allergy, Urticaria, Conjunctivitis, Runny Nose, Diathesis, Allergic Conjunctivitis, Pollinosis, Dermatitis, Allergic Runny nose