Аромазин®

General characteristics. Structure:

International unlicensed name: эксеместан
Dosage form: tablets, coated

Active agent: эксеместан 25 mg;
Excipients: Mannitolum of 26,0 mg, a gipromelloza of 1,50 mg, polysorbate – 80 0,125 mg, кросповидон 2,125 mg, silicon dioxide of colloid 0,125 mg, cellulose of microcrystallic 4,625 mg, carboxymethylstarch of sodium of 2,375 mg, magnesium stearate of 0,625 mg.

Structure of a sugar cover: a gipromelloza of 1,81 mg, a simetikonovy emulsion of 0,009 mg, a macrogoal – 6000 0,181 mg, magnesium a carbonate of 1,157 mg, titanium dioxide of 3,453 mg, methylparahydroxybenzoate of 0,003 mg, polyvinyl alcohol of 0,697 mg, sucrose of 30,19 mg;

(components for gloss giving: wax of cetylradio 0,0175 mg, talc of 0,01 mg, wax of karnaubsky 0,0225 mg.)

The structure blackened: shellac, ethanol, isobutanol, dye ferrous oxide (Е 172), titanium dioxide (Е 171).

Description
The round, biconvex tablets of color, white or white with a grayish shade, covered with a sugar cover with marking "7663" on one party executed by black paint.

Pharmacological properties:

Pharmacodynamics. Eksemestan - the irreversible steroid inhibitor of aromatase similar on structure to natural substance androstendion.

At women in a postmenopause estrogen is produced preferential by transformation of androgens into estrogen under the influence of aromatase enzyme in peripheral fabrics. Blocking of formation of estrogen by inhibition of aromatase is an effective and selective method of treatment of a hormonedependent breast cancer at women in a postmenopause. The mechanism of effect of the drug Aromazin® is caused by what it is irreversible contacts an active fragment of enzyme, causing its inactivation. At women in a postmenopause of Aromazin® authentically reduces concentration of estrogen in blood serum, since a dose of 5 mg, and the maximum decrease (> 90%) is reached at use of doses of 10-25 mg. At the patients in a postmenopause having a breast cancer, receiving 25 mg of drug daily the general level of enzyme of aromatase in an organism decreased by 98%.

Eksemestan has no progestogenny and oestrogenic activity. Only insignificant androgenic activity comes to light, it is preferential at use of high doses. Аромазин® does not exert impact on biosynthesis of cortisol and Aldosteronum in adrenal glands that confirms selectivity of effect of drug. In this regard there is no need for replacement therapy by glucocorticoids and mineralokortikoida.

At drug use even in low doses insignificant increase in levels of the luteinizing hormone (LH) and follicle-stimulating hormone (FSG) is observed in

to blood serum that is characteristic of drugs of this pharmacological group and probably develops by the principle of feedback at the level of a hypophysis: decrease in concentration of estrogen stimulates secretion of gonadotrophins in a hypophysis as well at women in a postmenopause.


Pharmacokinetics. After intake эксеместан it is quickly soaked up, generally from digestive tract. Absolute bioavailability of drug is not established. Assume that it is limited to extensive effect of the first passing through a liver. At a single dose of a dose of 25 mg the maximum concentration in plasma, equal 17 ng/ml, are reached in 2 hours. The concomitant use of food increases bioavailability of drug by 40%.

Pharmacokinetic parameters have linear character. The final elimination half-life makes about 24 hours. Communication with proteins of plasma - about 90%. Eksemestan and its metabolites do not contact erythrocytes. At repeated reception of not predicted cumulation of an eksemestan it is not observed.

Process of biotransformation of an eksemestan is carried out by oxidation of methylene group in 6 positions under the influence of an isoenzyme of CYP3A4 and/or recovery 17 ketogroups under the influence of aldoketoreductase with the subsequent conjugation. Products of metabolism of an eksemestan either are inactive, or are less active concerning aromatase inhibition, than initial connection.

Approximately equal quantities of an eksemestan (about 40%) are removed with urine and a stake within a week. From 0,1 to 1% are removed with urine in an invariable look.

To the expressed communication between system influence of drug and age it is not established.

At patients with a heavy renal failure (the clearance of creatinine (CC) <30 ml/min.) system influence of an eksemestan is twice higher, however dose adjustment is not required.

At patients with a moderate or heavy liver failure system influence of an eksemestan is 2 - 3 times higher, however dose adjustment is not required

Indications to use:

Widespread breast cancer at women in the natural or induced postmenopause, including when progressing a disease against the background of anti-oestrogenic therapy, and also when progressing a disease after numerous use of different types of hormonal therapy.

Adjuvant therapy of an early breast cancer at women in a posmenopauza about estrogen - positive receptors or with the unknown receptor status, after end 2-3 summer initial adjuvant therapies by Tamoxifenum, for the purpose of decrease in risk of a recurrence (remote or regional), and also a contralateral breast cancer.

Route of administration and doses:

Inside. Adults and patients of advanced age
The recommended dose makes 25 mg of 1 times a day, it is desirable after food.

At patients of patients with an early breast cancer treatment by drug is recommended to continue yes those a time until the general duration of consecutive adjuvant hormonal therapy reaches 5 years. Treatment of patients with a widespread breast cancer – long. At emergence of signs of progressing of a tumoral disease or at emergence of a contralateral breast cancer treatment of Aromazinom® should be stopped.

Liver or renal failure
Dose adjustment is not required.

Children. It is not recommended to use at children.

Features of use:

Аромазин® women should not appoint with the premenopauzalny endocrine status therefore when it is clinically proved, the post-menopausal status should be confirmed with determination of the LG, FSG level and oestradiol.

Аромазин® it is not necessary to appoint along with the drugs containing estrogen.

Due to the powerful estrogenponizhayushchy action of an eksemestan reduction of mineral density of a bone tissue is possible. Prior to adjuvant therapy eksemestany carrying out densitometry for assessment of mineral density of a bone tissue at women with osteoporosis or the increased risk of osteoporosis is recommended. During treatment eksemestany special observation of women with osteoporosis with purpose of the corresponding therapy is necessary.

Patients need to be warned about a possibility of emergence during treatment of Aromazinom® of drowsiness, an adynamy and dizziness. At emergence of these symptoms patients are recommended to refrain from driving and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Generally portability of Aromazina® good; undesirable effects at use of drug in a dose of 25 mg/days generally insignificant or moderately expressed.

The undesirable reactions distributed on systems of an organism and frequency are listed below: very often (> 10%), it is frequent (> 1%, <10%), infrequently (> 0,1%, <1%), is rare (> 0,01%, <0,1%).

From system of digestion: very often – nausea; often – anorexia, pain in a stomach, vomiting, a lock, dyspepsia, diarrhea, increase in appetite; infrequently – an ulcer желудка*.

From the central and peripheral nervous system: very often – sleeplessness, a headache; often – a depression, alarm, confusion of consciousness, dizziness, a syndrome of a carpal tunnel, paresthesia, a hypesthesia, an adynamy; infrequently - neuropathy.

From vascular system: very often – "inflows".

From skin and skin appendages: very often – perspiration; often – rash, an itch, dermatitis, an alopecia.

From a musculoskeletal system: very often – joint and skeletal and muscular pains (including an arthralgia, extremity pain, a dorsodynia, arthritis, a mialgiya, rigidity of joints); often - an osteoarthrosis, osteoporosis, osteochondrosis, pathological fractures.

From an organ of sight: often – a vision disorder

From cardiovascular system: very often – increase in arterial pressure.

From a respiratory organs: often – short wind, cough, bronchitis, sinusitis, pharyngitis, rhinitis, thorax pain, upper respiratory tract infections.

From urinogenital system: often - infections of uric ways.

Disturbances from blood and lymphatic system: often - a limfedema.

Others: very often – increased fatigue, it is frequent – pain of not specified localization, peripheral hypostases or hypostases of legs, a grippopodobny syndrome, fever, the general weakness, infections.

Approximately at 20% of patients (especially at patients with an initial lymphopenia) it was observed

periodic decrease in number of lymphocytes. However the average of lymphocytes at these patients significantly did not change over time, and the accompanying increase in incidence of viral infections was not observed.

Sometimes observed increase in activity of "hepatic" enzymes and an alkaline phosphatase, it is preferential at patients with metastasises in a liver and in a bone, and also in the presence of other damages of a liver (it is not established whether these changes are connected with administration of drug or not).

* most of patients had the ulcer anamnesis or received therapy by non-steroidal anti-inflammatory drugs.

Post-market researches:

Within clinical trials and at a post-marketing stage exceptional cases of hepatitis, including cholestatic hepatitis were observed.

Interaction with other medicines:

The drugs containing estrogen completely level pharmacological action of an eksemestan.

Drug is exposed to metabolism under the influence of P450 (CYP) cytochrome 3A4 and aldoketoreductases, and does not inhibit any of the main CYP isoenzymes. The specific inhibition of an isoenzyme of CYP3A4 ketokonazoly does not exert reliable impact on pharmacokinetics of an eksemestan. Despite the established pharmacokinetic interaction of an eksemestan with rifampicin, the strong inductor of an isoenzyme CYP3A4, pharmacological activity of Aromazina® (suppression of estrogen) remains without changes therefore dose adjustment is not required.

Contraindications:

Hypersensitivity to an eksemestan or to any other component of drug. Premenopazualny endocrine status. Pregnancy and period of a lactation

With care. Abnormal liver function or почекю Pregnancy and period of a lactation

Use of an eksemestan during pregnancy is forbidden in connection with potential risk for a fruit. Also it is not necessary to appoint drug during breastfeeding.

Overdose:

The single dose of drug which could cause emergence of life-threatening symptoms is not established. Use of an eksemestan in a single dose to 800 mg at healthy women and in a daily dose to 600 mg at women in a postmenopause with a widespread breast cancer was well transferred. There are no specific antidotes.

Treatment: symptomatic under regular control of the vital functions and careful observation.

Storage conditions:

At a temperature not above 30 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated 25 mg. On 15 tablets in the blister from PVDH / PVC – PVDH of aluminum foil; 1, 2 or 6 blisters together with the application instruction place in a cardboard pack.