Letromara 2.5 mg 30 tablets — Made in Ukraine — Free Delivery

Pharmacological properties

Pharmacodynamics. Letrozole - a non-steroidal aromatase inhibitor (inhibitor of estrogen biosynthesis); anticancer preparation.

Letrozole inhibits aromatase by competitive binding with the subunit of this enzyme - cytochrome P450 heme, which leads to a decrease in estrogen biosynthesis in all tissues.

In healthy postmenopausal women, a single dose of letrozole of 0.1 mg or 0.5 mg or 2.5 mg reduces plasma levels of estrone and estradiol (compared with the initial level) by 75–78 and 78%, respectively ... The maximum decrease is achieved after 48–78 hours.

In women with advanced postmenopausal breast cancer, daily use of letrozole at a dose of 0.1–5 mg reduces plasma levels of estradiol, estrone and estrone sulfate by 75–95% of the initial level.

Letrozole is a highly specific inhibitor of aromatase activity. Disruptions in the synthesis of steroid hormones in the adrenal glands have not been identified. In postmenopausal patients treated with letrozole in a daily dose of 0.1–5 mg, clinically significant changes in plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH, and renin activity were not detected. Conducting a stimulation test with ACTH after 6 and 12 weeks of therapy with letrozole at a daily dose of 0.1; 0.25; 0.5; one; 2.5 and 5 mg did not show any noticeable decrease in the synthesis of aldosterone or cortisol.

In healthy postmenopausal women after a single use of letrozole in doses of 0.1; 0.5 and 2.5 mg changes in the concentration of androgens (androstenedione and testosterone) in the blood plasma were not detected. In patients who received letrozole in a daily dose of 0.1–5 mg, changes in the level of androstenedione in the blood plasma were also not determined. In patients treated with letrozole, there were no changes in the concentrations of LH and FSH in the blood plasma and changes in the functions of the thyroid gland, which were assessed by the level of TSH, T4 and T3.

Pharmacokinetics. Letrozole is rapidly and completely absorbed in the gastrointestinal tract (the average bioavailability is 99.9%). Food intake slightly reduces the rate of absorption, so letrozole can be used independently of food.

The binding of letrozole to blood plasma proteins is about 60% (mainly with albumin - 55%). The concentration of letrozole in erythrocytes is almost 80% of the level in blood plasma. Letrozole is rapidly and completely distributed in tissues and is largely metabolized to form a pharmacologically inactive carbinol compound.

The metabolic clearance of letrozole is 2.1 l / h, which is less than the hepatic blood flow (about 90 l / h). It was revealed that the transformation of letrozole into a metabolite is carried out under the influence of isoenzymes CYP 3A4 and CYP 2A6 of cytochrome P450. The formation of a small amount of other, as yet unidentified metabolites, as well as the excretion of the unchanged preparation in the urine and feces, play an insignificant role in the total elimination of letrozole. The estimated final T½ from blood plasma is about 2 days.

Pharmacokinetics in selected patient groups. In studies that were conducted with the participation of volunteers with different states of renal function (24-hour creatinine clearance varied from 9 to 116 ml / min), it was found that after a single dose of letrozole at a dose of 2.5 mg, its pharmacokinetics did not change. In a similar study, conducted with the participation of volunteers with different states of liver function, it was found that in individuals with moderately severe liver dysfunction (class B on the Child-Pugh scale), the average AUC values ​​were 37% higher than in healthy individuals, but remained within the range of values ​​that were noted in individuals without impaired liver function. In a study of the pharmacokinetics of a single dose in patients with cirrhosis of the liver and severely impaired liver function (class C on the Child-Pugh scale), an increase in AUC was determined by 95% and T½ - by 187%, respectively, compared with those in healthy volunteers. Due to the fact that no increase in toxicity indicators was found in patients receiving doses of 5-10 mg / day, dose adjustment towards its reduction is not justified, although patients should be closely monitored by doctors. In addition, there was no evidence of any effect of renal dysfunction (calculated creatinine clearance values ​​were 20–50 ml / min) or liver dysfunction on plasma letrozole concentration in patients with common forms of breast cancer. The pharmacokinetics of letrozole does not depend on age.

Indications

Therapy for hormone-dependent advanced breast cancer of the first degree of the disease in the postmenopausal period. treatment of common forms of breast cancer in postmenopausal women (natural or artificially induced) who have previously received anti-estrogen therapy. adjuvant therapy for early-stage hormone-positive breast cancer in postmenopausal women.

Advanced adjuvant therapy for early-stage breast cancer in postmenopausal women undergoing standard adjuvant tamoxifen therapy. Neoadjuvant therapy in postmenopausal women with localized hormone-positive breast cancer, with the possibility of further surgical treatment in the case when surgical treatment was not indicated prior to therapy with Letromar. Further therapy after surgical treatment should be in accordance with the accepted standard for the postoperative period.

Application

Adults and elderly patients. the recommended dose is 2.5 mg once a day every day. with adjuvant and extended therapy, treatment should be continued for 5 years or until a relapse of the disease occurs. Following standard adjuvant tamoxifen therapy, follow-up and treatment with letromar should be continued for 4 years or until disease recurrence occurs. in patients with metastases, therapy should be continued until signs of disease progression become evident. during preoperative preparation, regular observation of patients is recommended. for elderly patients, dose adjustment of the preparation is not required.

Patients with impaired liver and / or kidney function. For patients with impaired liver function (class A or B on the Child-Pugh scale) or kidneys (with creatinine clearance ≥10 ml / min), dose adjustment is not required.

Contraindications

Hypersensitivity to the active substance or any component of the preparation. endocrine status is characteristic of the premenopausal period. pregnancy or lactation. patients with severe hepatic impairment (class C on the child's scale - I drink). preoperative use of the preparation if the status of the receptors is negative or unknown.

Side effects

When assessing the frequency of occurrence of various adverse reactions, the following gradations were used:

very often - ≥10%, often - 1-10%, sometimes - 0.1-1%, rarely - 0.01-0.1%, very rarely - 0.01%, including isolated cases.

Infections and invasions: sometimes - infections of the urinary system.

Benign, malignant and unidentified neoplasms, including cysts and polyps: sometimes - pain in tumor foci (patients with metastases / neoadjuvant therapy).

From the circulatory and lymphatic system: sometimes - leukopenia, thrombocytopenia.

Metabolic disorders: often - anorexia, increased appetite, hypercholesterolemia; sometimes - generalized edema, impaired lipid metabolism.

Mental disorders: often - depression; sometimes - increased excitement (including nervousness, irritability), anxiety.

From the nervous system: often - headache, dizziness; sometimes - drowsiness, insomnia, memory impairment, dysesthesia (including paresthesia, hypoesthesia), impaired taste perception, acute cerebrovascular disorders.

From the side of the organ of vision: sometimes - cataract, irritation of the mucous membrane of the eye, blurred vision, retinal thrombosis, retinal detachment.

From the side of the cardiovascular system: sometimes - palpitations, tachycardia, thrombophlebitis (including thrombophlebitis of superficial and deep veins), hypertension, cases of cardiac ischemia with adjuvant therapy; regardless of the causal relationship, the following adverse reactions were noted: thromboembolic reactions, angina pectoris, myocardial infarction and heart failure. With extended adjuvant therapy, the following adverse reactions were determined: newly diagnosed angina pectoris or worsening of its course, angina pectoris requiring surgery, myocardial infarction, thromboembolic disorders, ischemic stroke / transient cerebrovascular accident; rarely - pulmonary embolism, pulmonary hypertension, arterial thrombosis, stroke, arrhythmia, pericarditis, cerebrovascular infarction.

From the respiratory system: sometimes - shortness of breath, cough, interstitial lung disease.

From the digestive system: often - nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes - abdominal pain, stomatitis, dry mouth.

On the part of the hepatobiliary system: sometimes - an increase in the level of hepatic enzymes; very rarely - hepatitis.

On the part of the skin: often - alopecia, increased sweating, rash (including erythematous, maculopapular, psoriasis-like and vesicular rashes); sometimes - itching, dry skin, hives; very rarely - angioedema, anaphylactic reactions, toxic epidermal necrolysis, erythema multiforme.

From the musculoskeletal system: very often - arthralgia; often - myalgia, bone pain, osteoporosis, bone fractures; sometimes arthritis.

From the urinary system: sometimes - frequent urination.

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

General disorders: very often - hot flushes; often - fatigue (including asthenia and anxiety, peripheral edema, weight gain; sometimes - fever, dryness of the mucous membrane, thirst, weight loss.

Special instructions

There are no data on the use of letrozole in patients with creatinine clearance of 10 ml / min, therefore, before prescribing the preparation, the ratio of the expected effect of treatment and the potential risk should be assessed.

There is evidence of the occurrence of osteoporosis and / or bone fracture with the use of the preparation. In this regard, during therapy, it is recommended to monitor the state of the bone tissue.

The physician should justify the need to use appropriate contraception for women of reproductive age (including women in the premenopausal period or women who have recently entered the postmenopausal period) before confirming their postmenopausal status.

The preparation contains lactose, therefore, the preparation should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy and lactation. The preparation is contraindicated during pregnancy and lactation.

Children. The preparation is not used in pediatric practice.

The ability to influence the reaction rate when driving or working with other mechanisms. During treatment with letrozole, side effects from the central nervous system (dizziness, drowsiness, blurred vision) are possible, affecting the reaction rate, therefore, you should refuse to drive vehicles and work with complex mechanisms.

Interactions

There is no clinical experience regarding the use of letromar in combination with other antineoplastic agents.

According to the results of in vitro studies, letrozole inhibits the activity of cytochrome P450 isoenzymes - CYP 2A6 and CYP 2C19 (and the latter is moderate). The isoenzyme CYP 2A6 does not play a major role in preparation metabolism. In vitro experiments have shown that letrozole, which is used at concentrations 100 times higher than the equivalent values ​​in blood plasma, is not able to significantly inhibit the metabolism of diazepam (a substrate for CYP 2C19). Thus, clinically significant interactions with the CYP 2C19 isoenzyme are unlikely. However, caution should be exercised with the simultaneous use of letrozole and preparations that are metabolized predominantly with the participation of the above isoenzymes, which have a small range of therapeutic concentrations.

With the simultaneous use of letrozole with cimetidine or warfarin, a clinically significant interaction has not been established.

There was no interaction with benzodiazepine, barbiturates, NSAIDs, furosemide, omeprazole.

Overdose

In clinical studies, the highest single and multiple doses of letrozole tested in healthy volunteers were 30 and 5 mg, respectively, the latter was also tested in postmenopausal breast cancer patients. each of these doses was well tolerated. there is no clinical evidence for an individual dose of the preparation that would result in life-threatening symptoms.

Specific treatment methods are unknown, in case of overdose, therapy should be symptomatic and supportive.

Storage conditions

In a dark place at a temperature not exceeding 25 ° c.