Anastrozol

General characteristics. Structure:

Active ingredient: 0,25 mg or 1 mg of an anastrozol.

Excipients: magnesium stearate, Kollidon CL (кросповидон), FD&C Yellow nr dye. 5, Ludipresso (lactose, povidone, кросповидон).

Antineoplastic means.

Pharmacological properties:

Pharmacodynamics. Anastrozol treats new generation of nonsteroid inhibitors of aromatase, applied at the disseminated cancer of mammary glands at women in the postmenopauzny period. Under the influence of an anastrozol estrogenozavisimy reproduction and growth of cells of mammary glands is inhibited. The mechanism of action of an anastrozol is connected with the selection inhibition of aromatase, enzyme of system of P450 cytochrome. The main source of the circulating estrogen at women in a postmenopause androgens, first of all, androstendion and testosterone are. Aromatase provides their multiple hydroxylation with transformation into estrone, and then into oestradiol in fatty and muscular tissue, a liver, adrenal glands and in tumoral fabric.

Anastrozol selectively inhibits aromatase by competitive linkng with iron atom P450 cytochrome gem. In such a way drug inhibits activity of enzyme that leads to the maximum decrease in level of estrogen both in a peripheral blood-groove, and in fabrics of a tumor and renders therapeutic effect at patients with cancer of a mammary gland. In a postmenopause анастрозол in a daily dose of 1 mg causes decrease in level of oestradiol by 80% in women. Nonsteroid inhibitors, in comparison with aromatase inactivators, have reversible action and depends on drug presence.

Anastrozol has no progestagenny, androgenic and oestrogenic activity. Drug does not influence secretion of cortisol and Aldosteronum.

Pharmacokinetics. After intake анастозол it is soaked up quickly and completely from digestive tract. Food slightly reduces the absorption speed, but not its degree and does not lead to clinically significant influence on equilibrium concentration of drug in plasma at a single dose of a daily dose. Cmax  is reached in 2 h (on an empty stomach). In blood about 40% contact proteins of plasma. Equilibrium concentration in blood at daily reception is reached approximately in 7 days. There are no data on cumulation of drug and dependence of pharmacokinetic parameters of an anastrozol on time or a dose. Metabolism of an anastrozol is carried out by N-dealkylation, a hydroxylation and a glyukuronization with formation of inactive metabolites, basic of which — triazole which does not inhibit aromatase, but is defined in plasma and urine. Anastozol and his metabolites are removed slowly, preferential with urine (less than 10% in not changed look) during 72 h after reception. The elimination half-life makes 40-50 h. The clearance of an anastrozol after oral administration at cirrhosis or a renal failure does not change. The pharmacokinetics of an anastrozol does not depend on age of women in a menopause.

Indications to use:

Treatment of common forms of a breast cancer at women in a postmenopause (natural or caused artificially).

Breast cancer at women in a postmenopause with progressing of a disease against the background of other anti-estrogen.

Route of administration and doses:

Inside. To swallow a tablet entirely, washing down with water. It is recommended to accept drug at the same time.

At the disseminated forms of cancer of mammary glands at women in a postmenopause (adults and advanced age) the recommended dose of an anastozol makes 1,0 mg once a day, a long time. At emergence of signs of progressing of a disease administration of drug should be stopped.

At patients with lungs and moderately expressed renal failures, and also with easy extent of disorder of function of a liver correction of a dose is not required.

Features of use:

It is not recommended to apply at women in the reproductive period. In case of doubts in the hormonal status of the patient the menopause has to be confirmed with definition of sex hormones in blood serum.

There are no sufficient data about use of an anastozol for patients with average or heavy degree of abnormal liver functions or at patients with the expressed renal failures (Cl a kreatininabezopasnost and efficiency at children is not established.

In case of the remaining uterine bleeding against the background of reception of an anastrozol consultation and observation of the gynecologist is necessary.

Reducing the level of the circulating oestradiol, анастрозол can cause decrease in mineral density of a bone tissue. At the patients having osteoporosis or having risk of development of osteoporosis, the mineral density of a bone tissue has to be estimated by a densitometry method (for example DEXA scanning) in an initiation of treatment and in dynamics. If necessary treatment or prevention of osteoporosis under careful observation of the doctor have to be begun.

Influence on ability to driving of motor transport and to control of mechanisms. Some side effects of an anastozol, such as adynamy and drowsiness, can negatively influence ability of performance of potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Anastozol can cause the following collateral reactions with a different frequency (very often (> 10%); often (from 1 to 10%); seldom (from 0,1 to 1%); very seldom (

- from reproductive system: often – dryness of a vagina; seldom – vulval bleedings (generally within the first weeks after cancellation or change of the previous hormonal therapy on анастрозол);

- from system of digestion: often – nausea, diarrhea; seldom – anorexia, vomiting, increase in activity of gamma glutaminetransferase and ShchF;

- from vascular system: very often – "inflows";

- from a nervous system: often – a headache, an adynamy; seldom – drowsiness;

- from a musculoskeletal system: often – an arthralgia; seldom – administration of drug can cause decrease in mineral density of a bone tissue in connection with decrease in level of the circulating oestradiol, thereby increasing risk of developing of osteoporosis and fractures of bones;

- from skin and skin appendages: often – thinning of hair;

- from metabolism: seldom – a hypercholesterolemia;

- allergic reactions: often – skin rash; very seldom – a small tortoiseshell, a polymorphic erythema, Stephens-Johnson's syndrome, angioedy and an acute anaphylaxis.

Interaction with other medicines:

The drugs containing estrogen reduce pharmacological action of an anastrozol in this connection they should not be appointed at the same time. It is not necessary to appoint Tamoxifenum along with anastrozoly as it can weaken pharmacological action of the last.

Contraindications:

Anastrozol is contraindicated:

- at women in a premenopauza;

- at pregnancy and a lactation;

- at the expressed renal failure (creatinine Cl less than 20 ml/min.);

- at the moderated or expressed liver failure (safety and efficiency is not established);

- at hypersensitivity to an anastrozol or other components of drug.

Overdose:

There are no data on overdose.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 0,25 mg and 1,0 mg. On 10 or 20 tablets in blisters. On 5, 15, 25, 50, 100, 500 tablets in packages or on 5, 15, 25, 50, 100 tablets in bottles.