Anastrozol

General characteristics. Structure:

Active ingredient: 1 mg of an anastrozol.
 
Excipients: lactoses monohydrate, povidone, carboxymethylstarch of sodium, magnesium stearate.
 
Structure of a film cover: Опадрай white (white are a part of Opadraya: gipromelloza, macrogoal, titanium dioxide).

Pharmacological properties:

Pharmacodynamics. Anastrozol is the high-selection inhibitor of aromatase - enzyme by means of which at women in a postmenopause androstendion in peripheral fabrics turns into estrone and further into oestradiol. Decrease in concentration of the circulating oestradiol at patients with cancer of a mammary gland renders therapeutic effect. In a postmenopause анастрозол in a daily dose of 1 mg causes decrease in concentration of oestradiol by 80% in women. Anastrozol has no progestogenny, androgenic and oestrogenic activity. Anastrozol in daily doses to 10 mg does not render effect on secretion of cortisol and Aldosteronum, therefore, at use of an anastrozol replaceable introduction of corticosteroids is not required.
 
Influence on the mineral density of a bone tissue. It is shown that at patients with a gormonopozitivny early breast cancer in a postmenopause who accept анастрозол changes of bone system can be prevented according to the standards established for treatment of patients with a certain risk of changes. So, advantage of an anastrozol in a combination from bisfosfonata (in comparison with therapy only anastrozoly) at patients with average and high risk of developing of fractures was shown in 12 months on indicators of mineral bone density, structural change of a bone tissue and markers of a bone resorption. Moreover, in group of low risk change of an indicator of mineral bone density against the background of therapy by one anastrozol and the supporting treatment by vitamin D and calcium was not noted.
 
Lipids. At therapy anastrozoly, including, at inclusion in combinations from bisfosfonata, changes of concentration of lipids in plasma are not revealed.

Pharmacokinetics. Absorption of an anastrozol bystry, the maximum concentration in plasma is reached within 2 hours after intake (on an empty stomach). 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 of an anastrozol. After 7-day administration of drug about 90-95% of equilibrium concentration of an anastrozol in plasma are reached. There are no data on dependence of pharmacokinetic parameters of an anastrozol from time or a dose.
 
The pharmacokinetics of an anastrozol does not depend on age of women in a postmenopause. Pharmacokinetics of an anastrozol at children were not studied.
 
Communication with proteins of a blood plasma - 40%.
 
Anastrozol is brought slowly, plasma elimination half-life makes 40-50 hours. It is extensively metabolized at women in a postmenopause. Less than 10% of a dose are allocated with urine in an invariable look within 72 hours after administration of drug. Metabolism of an anastrozol is carried out by N-dealkylation, a hydroxylation and a glyukuronization. Metabolites are removed preferential with urine. Triazole, the main metabolite defined in plasma does not inhibit aromatase. The clearance of an anastrozol after oral administration at cirrhosis or a renal failure does not change.

Indications to use:

- Adyyuvantny therapy of an early gormonopolozhitelny breast cancer at women in a postmenopause (including after 2-3-year-old adjuvant therapy by Tamoxifenum).
- The first line of therapy of a locally-spread or metastatic breast cancer, with positive or unknown hormonal receptors at women in a postmenopause.
- The second line of therapy of the widespread breast cancer progressing after treatment by Tamoxifenum.

Route of administration and doses:

Inside. To swallow a tablet entirely, washing down with water. It is recommended to accept drug in one and too time.
 
Adults, including elderly: on 1 mg in 1 times a day it is long. At emergence of signs of progressing a disease administration of drug should be stopped.
 
As adjuvant therapy the recommended treatment duration - 5 years.
 
Use for special groups of patients. Renal failures: dose adjustment with easy and average degree of a renal failure is not required from patients.

Abnormal liver functions: correction of a dose with easy degree of a liver failure is not required from patients. There are no data on use of an anastrozol for patients with a heavy liver failure or with a heavy renal failure (clearance of creatinine less than 20 ml/min.).
 
Children: Safety and efficiency at children is not established.

Features of use:

Pregnancy and lactation. Use of an anastrozol is contraindicated at pregnancy and during breastfeeding.

At women about a receptor - a negative tumor to estrogen efficiency of an anastrozol was not shown, except those cases when the previous affirmative clinical answer on Tamoxifenum was observed.
 
In case of doubts in the hormonal status of the patient the menopause has to be confirmed by definition of sex hormones in blood serum.
 
In case of the remaining uterine bleeding against the background of reception of an anastrozol consultation and observation of the gynecologist is necessary.
 
The drugs containing estrogen should not be appointed along with anastrozoly as these drugs will level its pharmacological action.
 
Reducing concentration of the circulating oestradiol, анастрозол can cause decrease in mineral density of a bone tissue with the subsequent increase in risk of a change. Patients with such high risk are subject to treatment according to the guide to therapy of these complications.
 
At patients with osteoporosis or risk of development of osteoporosis the mineral density of a bone tissue has to be estimated by a densitometry method, for example, DEXA scanning (Dual-Energy X-ray Absorptiometry - a two-power x-ray absorbtsiometriya), 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.
 
There are no data on simultaneous use of an anastrozol and drugs analogs LGRG (rileasing-hormone of luteinizing hormone).
 
It is unknown whether improves анастрозол results of treatment when sharing with chemotherapy.
 
Data on safety at prolonged treatment anastrozoly are not obtained yet. At use of an anastrozol more often than at therapy Tamoxifenum, observed ischemic diseases, however the statistical importance at the same time is noted.
 
Efficiency and safety of an anastrozol and Tamoxifenum at their simultaneous use regardless of the status of hormonal receptors are comparable with those when using one Tamoxifenum. The exact mechanism of this phenomenon is not known yet.
 
There are no data on use of an anastrozol for patients with heavy degree of an abnormal liver function.
 
Influence on ability to manage vehicles and mechanisms. Some side effects of an anastrozol, such as adynamy and drowsiness, can negatively influence ability of performance of potentially dangerous types of activity demanding the increased concentration, attention and speed of psychomotor reactions. In this regard, at emergence of these symptoms it is necessary to refrain from performance of the specified types of activity.

Side effects:

During clinical trials and post-marketing experience of use of an anastrozol the following side reactions were observed (frequency of reactions is defined as follows: very often (> 1/10), it is frequent (> 1/100 <1/10), infrequently (> 1/1000 <1/100), is rare (> 1/10000 <1/1000), is very rare (<1/10000, including separate messages):
 
Disturbances from vessels: very often - "inflows", increase in arterial pressure; often - thrombophlebitis, venous thrombosis, a thromboembolism of deep veins, disturbance of cerebral circulation (stroke), stenocardia, a myocardial infarction.
 
Disturbances from skeletal and muscular and connecting fabric: very often - a dorsodynia, arthralgia / constraint of joints, arthritis, osteoporosis, fractures; often - an ostealgia, arthrosis, a mialgiya; infrequently - a trigger finger.
 
Disturbances from generative organs and a mammary gland: often - dryness of a mucous membrane of a vagina, vulval bleedings (generally within the first weeks after cancellation or change of the previous hormonal therapy on анастрозол), a leukorrhea, pains in mammary glands, a vaginitis, a vulvovaginitis.
 
Disturbances from skin and hypodermic fabrics: very often - skin rash; often - thinning of hair (alopecia), allergic reactions, the increased sweating, an itch; infrequently - a small tortoiseshell; seldom - a multiformny erythema, anaphylactoid reaction, a skin vasculitis (including separate cases of a purpura (Shenleyna-Genokh's syndrome)); very seldom - Stephens-Johnson's syndrome, a Quincke's disease.
 
Disturbances from digestive tract: very often - nausea; often - diarrhea, vomiting, abdominal pains, a lock, dyspepsia, dryness of a mucous membrane of an oral cavity.
 
Disturbances from a liver and biliary tract: often - increase in activity of an alkaline phosphatase, alaninaminotranspherase, aspartate aminotransferase, infrequently - increase in activity gamma глютамилтрансферазы and concentration of bilirubin, hepatitis.
 
Disturbances from a nervous system: very often - a headache, a depression, sleeplessness; often - dizziness, uneasiness, paresthesias, drowsiness, nervousness, a syndrome of a carpal tunnel (it was generally observed at patients with risk factors of this disease), a disorientation.

Disturbances from a metabolism and food: very often - peripheral hypostases; often - anorexia, increase in body weight, decrease in body weight, a hypercholesterolemia. Administration of drug can cause decrease in mineral density of a bone tissue in connection with decrease in concentration of the circulating oestradiol, thereby, increasing risk of developing of osteoporosis and fractures of bones; infrequently - a hypercalcemia (with or without increase in concentration of parathormone).

The general frustration and disturbances in an injection site: very often - an adynamy of easy or moderate degree of manifestation, pain; often - a grippopodobny syndrome, pains in a thorax, pains in the field of a basin, pains in a neck, fever.
 
Disturbances from blood and lymphatic system: very often - lymphatic hypostasis; often - anemia, a leukopenia.
 
Disturbances from respiratory system, bodies of a thorax and a mediastinum: very often - pharyngitis; often - strengthening of cough, short wind, sinusitis, bronchitis, rhinitis.
 
Disturbances from an organ of sight: often - a cataract.
 
Disturbances from kidneys and urinary tract: often - infections of urinary tract.
 
Injuries, intoxications and complications of manipulations: often - accidental injuries.

Interaction with other medicines:

Researches on medicinal interaction with phenazone and Cimetidinum indicate that combined use of an anastrozol with other drugs will hardly lead to clinically significant medicinal interaction mediated by P450 cytochrome.
 
Clinically significant medicinal interaction at reception of an anastrozol along with other often used drugs is absent.
 
At the moment there are no data on use of an anastrozol in a combination with other antineoplastic drugs.
 
The drugs containing estrogen reduce pharmacological action of an anastrozol in this connection, they should not be applied along with anastrozoly.
 
It is not necessary to apply Tamoxifenum along with anastrozoly as it can weaken pharmacological action of the last.

Contraindications:

- Hypersensitivity to an anastrozol or other components of drug.
- Pregnancy and period of feeding by a breast.
- Premenopauza.
- A heavy liver failure (safety and efficiency is not established).
- The accompanying therapy by Tamoxifenum or drugs containing estrogen.
- Children's age (safety and efficiency at children is not established).
 
With care:
- Heavy renal failure (clearance of creatinine less than 20 ml/min.).
- Osteoporosis.
- Hyper cholesteremia.
- Coronary heart disease.
- Abnormal liver function.
- Insufficiency of lactase, a lactose intolerance, glyukozo-galaktozny malabsorption (the dosage form of drug contains lactose).

Overdose:

Isolated clinical cases of accidental overdose of drug are described. The single dose of an anastrozol which could lead to symptoms life-threatening, is not established.

The specific antidote does not exist, in case of overdose treatment has to be symptomatic. It is possible to induce vomiting if the patient is in consciousness. Dialysis can be carried out. The general maintenance therapy, observation of the patient and control of function of vitals and systems is recommended.

Storage conditions:

In the dry, protected from light place at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity - 5 years. Not to accept after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 1 mg. On 10 or 14 tablets in a blister strip packaging. On 2 blister strip packagings on 14 tablets, or on 3 blister strip packagings on 10 tablets together with the application instruction in a pack from a cardboard.