Neksazol

Nexazol is an anticancer drug, a non-steroidal selective inhibitor of the action of aromatase (estrogen binding enzyme). It has anti-estrogenic activity.

The effect of aromatase is weakened by competitive synthesis with the prosthetic region (heme) of hemoprotein P450 (a subunit of this enzyme). In postmenopausal women, estrogens are formed mainly with the help of an aromatase enzyme that converts the androgens bound inside the adrenal glands (mainly testosterone with androstenedione) to estradiol with estrone.

Indications Neksazola

It is used for such pathologies:

• the early stages of breast carcinoma, whose cells have hormone-related endings (as an adjuvant course during postmenopausal);
• early phases of postmenopausal breast cancer (after the end of the standard adjuvant cycle using tamoxifen for 5 years);
• hormone-dependent types of breast carcinoma (common) in postmenopause (treatment of the 1st line);
• a hormone-dependent type of breast cancer of a common form (with artificially or naturally postmenopausal) in women who have previously been treated with anti-estrogens.

Release form

The release of drugs is implemented in tablets - 10 pieces inside the cell plate. Inside the box are 3 such records.

Pharmacodynamics

Daily use of letrozole in women during postmenopause at a dosage of 0.1-5 mg per day causes a decrease in estrone values with estradiol and estrone sulfate inside the blood plasma by 75-95% of the initial values. A low level of estrogen is maintained during therapy in all patients.

If a woman has an estrogen-dependent neoplasm of a malignant nature in the breast area (during menopause), the drug, reducing circulating estrogens and inhibiting their binding inside the tumor tissues, causes regression of the neoplasm (23% of these cases), as well as a decrease in the number of relapses and deaths Having a high specificity regarding aromatase, the drug does not violate the binding of steroid hormones inside the adrenal glands.

Letrozole can be used for postmenopausal in the absence of effect from the use of tamoxifen.

Pharmacokinetics

Absorption.

Letrozole is absorbed fully and at high speed inside the gastrointestinal tract. After eating on an empty stomach, Сmax values after 60 minutes are equal to 129 ± 20.3 nmol / l, and if introduced after 2 hours from the moment of taking food, Сmax LS is 98.7 ± 18.6 nmol / l. Changes in the values of AUC is not marked, because of which the medicine can be used without reference to food intake. Bioavailability scores are 99.9%.

Distribution processes.

Intlasma protein synthesis equals 60% (mainly associated with albumin - by 55%). The letrozole index inside erythrocytes is 80% of plasma values.

The level of apparent distribution volume after obtaining Vss indicators is 1.87 l / kg. With the daily use of a portion of 2.5 mg, stable equilibrium values are observed after 0.5-1.5 months. The altered equilibrium indices inside the plasma are approximately all above the level after administration of a 1-fold dosage (2.5 mg), as well as 1.5–2 times higher than the calculated mark - this indicates a certain non-linearity of the drug when using a 2.5 mg dose. Long reception does not lead to the accumulation of drugs.

Exchange processes and excretion.

The metabolic processes are mainly realized inside the liver with the help of the hemoprotein P450 ZA4 isoenzymes, as well as 2A6 with the formation of a carbinol derivative that does not have a medicinal effect.

The drug is excreted mainly through the kidneys in the form of metabolic components, and in addition through the intestines. The term half-life is 48 hours. The substance can be excreted from plasma by hemodialysis.

Dosing and administration

Nexazol should be taken orally - 1 tablet (2.5 mg) 1 time per day.

As an agent for adjuvant procedures, the drug has been used for a 5 year term. If the patient has symptoms of progression of the pathology, the medication is canceled.

[1]

Use Neksazola during pregnancy

Nexazol is not used during pregnancy or breastfeeding, as well as during premenopause.

Contraindications

The main contraindications:

• severe intolerance associated with elements of the drug;
• endocrine indicators that correspond to the reproductive period;
• premenopause.

Side effects Neksazola

Among the adverse events:

• test data: weight gain is often noted. Sometimes weight loss occurs;
• lesions affecting the work of the cardiovascular system: sometimes there is angina or tachycardia, and in addition, thromboembolism, HF with thrombophlebitis (deep or superficial veins) or myocardial infarction with palpitations and increased blood pressure values. Rarely, pulmonary embolism, arterial thrombosis or cerebral infarction;
• disorders affecting lymph and blood: sometimes leukopenia develops;
• problems with the work of the National Assembly: dizziness or headaches are often noted. Sometimes there is a disorder of cerebral blood flow in the active phase, drowsiness, memory, taste or sensitivity disorders (including hypesthesia and paresthesia) and insomnia;
• visual impairment: sometimes there is a visual impairment, eye irritation or cataract;
• signs associated with the organs of the mediastinum and the sternum, as well as the respiratory system: sometimes there is a cough or dyspnea;
• lesions in the gastrointestinal tract: often vomiting, diarrhea, nausea, obstipation or dyspepsia. Sometimes stomatitis, abdominal pain and xerostomia develop;
• urination disorders: sometimes there is an increase in urination;
• disorders associated with the epidermis and the subcutaneous layer: mainly develops hyperhidrosis. Often there are rashes (maculopapular, vesicular, erythematous or psoriasis) or alopecia. Sometimes there is skin dryness or itching and urticaria;
• problems with the work of connective tissues along with the musculoskeletal structure: arthralgia mainly appears. Often, pain develops that affects the bones, osteoporosis, myalgia, or fractures. Arthritis is sometimes observed;
• Nutritional and metabolic disorders: the appetite is often increased and hypercholesterolemia or anorexia develops. Sometimes systemic edemas form;
• infection: infection sometimes appears;
• tumors of an unidentified, malignant or benign nature (among them polyps and cysts): sometimes pain develops at the site of the neoplasm;
• general disorders: mostly severe fatigue (also asthenia) or flushes. Often there is malaise or peripheral swelling. Sometimes dry mucous membranes, hyperthermia or thirst develops;
• impaired hepatobiliary function: sometimes there is an increase in the activity of intrahepatic enzymes;
• lesions associated with the mammary glands and reproductive activity: sometimes vaginal discharge or bleeding occurs, chest tenderness or vaginal dryness is noted;
• mental disorders: depression often develops. Sometimes there is irritability, anxiety and nervousness.

Overdose

There are only single data on intoxication. Special therapy is not carried out, perform only symptomatic and supportive actions.

Interactions with other drugs

In vitro, the substance letrozole slows down the action of the isoenzymes of the hemoprotein P450 - 2A6, as well as 2C19 (moderately). Component CYP2A6 has no significant effect on the metabolic processes of drugs. Therefore, it is necessary to very carefully combine Nexazol with substances with a low drug index, in which the distribution is largely determined by these isoenzymes.

[2], [3]

Storage conditions

Nexazol must be kept in a place that is closed to children. Temperature indicators - maximum 30 ° С.

Shelf life

Nexazol is allowed to apply for a 3-year period from the date of sale of the therapeutic product.

Application for children

The drug is not used in pediatrics.

Analogs

Analogs of drugs are substances Extrasa and Letroza.