Nexazole

Nexazole is an antitumor drug, a non-steroidal selective inhibitor of aromatase (an enzyme of estrogen binding). It has antiestrogenic activity.

The action 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 the aromatase enzyme, which converts androgens bound inside the adrenal glands (mainly testosterone with androstenedione) into estradiol with estrone.

Indications Nexazole

It is used for the following pathologies:

• early stages of breast carcinoma, the cells of which have hormone-associated endings (as an adjuvant course during postmenopause);
• early stages of postmenopausal breast cancer (after completion of a standard adjuvant cycle using tamoxifen for 5 years);
• hormone-dependent types of breast carcinoma (of widespread nature) in postmenopause (first-line treatment);
• a hormone-dependent type of breast cancer of a widespread form (with artificially provoked or natural postmenopause) in women who were previously treated with antiestrogens.

Release form

The drug is released in tablets - 10 pieces inside a cell plate. Inside the box - 3 such plates.

Pharmacodynamics

Daily use of letrozole in postmenopausal women at a dosage of 0.1-5 mg per day causes a decrease in the values of estrone with estradiol and estrone sulfate in the blood plasma by 75-95% of the initial values. Low estrogen levels are maintained during therapy in all patients.

In the case of a woman developing an estrogen-dependent malignant neoplasm in the breast area (during menopause), the drug, by reducing the levels of circulating estrogens and inhibiting their binding within tumor tissues, causes regression of the neoplasm (23% of such cases), as well as a decrease in the number of relapses and deaths. Having high specificity with respect to aromatase, the drug does not disrupt the binding of steroid hormones within the adrenal glands.

Letrozole can be used in postmenopausal women if tamoxifen is ineffective.

Pharmacokinetics

Absorption.

Letrozole is fully and rapidly absorbed in the gastrointestinal tract. After administration on an empty stomach, the Cmax values after 60 minutes are 129±20.3 nmol/l, and in the case of administration after 2 hours from the moment of food intake, the Cmax of the drug is 98.7±18.6 nmol/l. No changes in AUC values are noted, due to which the drug can be used without reference to food intake. Bioavailability indicators are 99.9%.

Distribution processes.

Intraplasmic protein synthesis is 60% (mainly bound to albumin - 55%). The letrozole index inside erythrocytes is 80% of the plasma values.

The apparent distribution volume level after obtaining Vss values is 1.87 l/kg. With daily use of a 2.5 mg dose, stable equilibrium values are observed after 0.5-1.5 months. The changed equilibrium values in plasma are approximately seven times higher than the level after administration of a single dose (2.5 mg), and also 1.5-2 times higher than the calculated mark - this indicates some nonlinearity of the drug when using a 2.5 mg dose. Long-term use does not lead to accumulation of the drug.

Metabolic processes and excretion.

Metabolic processes are mainly carried out inside the liver with the help of hemoprotein isoenzymes P450 3A4, as well as 2A6, with the formation of a carbinol derivative that does not have a medicinal effect.

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

Dosing and administration

Nexazole should be taken orally – 1 tablet (2.5 mg) once a day.

As a means for adjuvant procedures, the drug is used for a 5-year term. If the patient has symptoms of progression of the pathology, the drug is discontinued.

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Use Nexazole during pregnancy

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

Contraindications

Main contraindications:

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

Side effects Nexazole

Side effects include:

• Test data: weight gain is often observed. Sometimes weight loss occurs;
• lesions affecting the work of the cardiovascular system: sometimes angina or tachycardia appears, and in addition thromboembolism, heart failure with thrombophlebitis (deep or superficial veins) or myocardial infarction with palpitations and increased blood pressure. Rarely, pulmonary embolism, arterial thrombosis or cerebral infarction are observed;
• disorders affecting the lymph and blood: sometimes leukopenia develops;
• problems with the functioning of the nervous system: dizziness or headaches are often observed. Sometimes a disorder of cerebral blood flow in the active phase, drowsiness, disorders associated with memory, taste or sensitivity (including hypoesthesia and paresthesia) and insomnia develop;
• visual disturbances: sometimes blurred vision, eye irritation or cataracts may occur;
• signs associated with the organs of the mediastinum and sternum, as well as with the respiratory system: sometimes cough or dyspnea occurs;
• Gastrointestinal lesions: vomiting, diarrhea, nausea, constipation or dyspepsia often occur. Stomatitis, abdominal pain and xerostomia sometimes develop;
• urinary disorders: sometimes there is an increase in the frequency of urination;
• disorders related to the epidermis and subcutaneous layer: mainly hyperhidrosis develops. Rashes (maculopapular, vesicular, erythematous or psoriatic) or alopecia are often observed. Sometimes dry skin or itching and urticarial rashes occur;
• problems with the functioning of connective tissues together with the musculoskeletal structure: arthralgia mainly appears. Often pain develops, affecting the bones, osteoporosis, myalgia or fractures. Sometimes arthritis is observed;
• nutritional and metabolic disorders: appetite often increases and hypercholesterolemia or anorexia develops. Sometimes systemic edema develops;
• Infections: Sometimes an infection occurs;
• tumors of an unspecified, malignant or benign nature (including polyps and cysts): sometimes pain develops at the site of the neoplasm;
• General disorders: usually severe fatigue (also asthenia) or hot flashes appear. Often malaise or peripheral edema is noted. Sometimes dry mucous membranes, hyperthermia or thirst develop;
• disorders of 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, breast tenderness or vaginal dryness is noted;
• Mental disorders: depression often develops. Sometimes irritability, anxiety and nervousness are observed.

Overdose

There are only isolated data on intoxication. No special therapy is carried out, only symptomatic and supportive actions are performed.

Interactions with other drugs

In vitro, letrozole inhibits the action of hemoprotein P450 isoenzymes - 2A6, as well as 2C19 (moderately). The CYP2A6 component does not have a significant effect on the metabolic processes of drugs. Therefore, it is necessary to be extremely careful when combining Nexazole with substances that have a low drug index, the distribution of which is largely determined by these isoenzymes.

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Storage conditions

Nexazole should be stored in a place closed to children. Temperature indicators - maximum 30°C.

Shelf life

Nexazole is permitted to be used for a period of 3 years from the date of sale of the therapeutic product.

Application for children

The medication is not used in pediatrics.

Analogues

The analogs of the drug are the substances Extrasa and Letroza.