Anastrozole - instructions for use, dose, side effects, contraindications

Anastrozole is a highly selective aromatase inhibitor, an enzyme that, with the help of which, in postmenopausal women, androstenedione in peripheral tissues is converted to estrone and further into estradiol. Reducing the concentration of circulating estradiol in patients with breast cancer has a therapeutic effect. In postmenopausal women anastrozole in a daily dose of 1 mg causes a decrease in the concentration of estradiol by 80%. Anastrozole does not possess progestogen, androgenic and estrogenic activity. Anastrozole in daily doses up to 10 mg does not have an effect on the secretion of cortisol and aldosterone, therefore, when anastrozole is used, it is not necessary to substitute corticosteroids.

Effect on bone mineral density

It was shown that in patients with hormone-positive early breast cancer in postmenopausal women who take anastrozole, changes in the bone system can be prevented in accordance with the standards established to treat patients with a certain risk of fractures. Thus, the advantage of anastrozole in combination with bisphosphonates (in comparison with anastrozole alone) in patients with an average and high risk of fracture was demonstrated after 12 months in terms of bone mineral density, structural changes in bone tissue and markers of bone resorption. Moreover, in the low-risk group, there was no change in bone mineral density in the context of single anastrozole therapy and vitamin maintenance treatment D and calcium.

Lipids

With anastrozole therapy, including, when taken in combination with bisphosphonates, no changes in plasma lipid concentrations were detected.

Pharmacokinetics:

Absorption of anastrozole is fast, the maximum concentration in the plasma is reached within 2 hours after ingestion (fasting).Food slightly reduces the rate of absorption, but not its degree and does not lead to a clinically significant effect on the equilibrium concentration of the drug in the plasma with a single daily intake of anastrozole. After a 7-day treatment, approximately 90-95% of the equilibrium concentration of anastrozole in plasma is achieved. There is no information on the dependence of pharmacokinetic parameters of anastrozole on time or dose.

The pharmacokinetics of anastrozole does not depend on the age of postmenopausal women. The pharmacokinetics of anastrozole in children have not been studied.

Connection with blood plasma proteins - 40%.

Anastrozole is withdrawn slowly, the half-life from the plasma is 40-50 hours. Extensively metabolized in postmenopausal women. Less than 10% of the dose is excreted unchanged in urine within 72 hours after taking the drug. Anastrozole metabolism is carried out N-dealkylation, hydroxylation and glucuronization. Metabolites are excreted mainly with urine. Triazole, the main metabolite, determined in plasma, does not inhibit aromatase. The clearance of anastrozole after oral administration with liver cirrhosis or renal dysfunction does not change.

Indications:

- Adjuvantnaya therapy of early hormone-positive breast cancer in postmenopausal women (including after 2-3 years of adjuvant therapy with tamoxifen).

- The first line of therapy for locally advanced or metastatic breast cancer, with positive or unknown hormonal receptors in postmenopausal women.

- The second line of therapy for advanced breast cancer progressing after treatment with tamoxifen.

Contraindications:

- Hypersensitivity to anastrozole or other constituents of the drug.

- Pregnancy and lactation.

- Premenopause.

- Severe hepatic insufficiency (safety and efficacy not established).

- Concomitant therapy with tamoxifen or preparations containing estrogens.

- Child age (safety and efficacy in children not established).

Carefully:

- Severe renal insufficiency (creatinine clearance less than 20 ml / min).

- Osteoporosis.

- Hypercholesterolemia.

- Cardiac ischemia.

- Violation of the function of the liver.

- Insufficiency of lactase, lactose intolerance, glucose-galactose malabsorption (in the drug form of the drug contains lactose).

Pregnancy and lactation:

The use of anastrozole is contraindicated in pregnancy and during breastfeeding.

Dosing and Administration:

Inside. Swallow the whole tablet with water. It is recommended to take the drug at the same time.

Adults, including the elderly: 1 mg orally once a day for a long time. If signs of disease progression appear, the drug should be discontinued.

As an adjuvant therapy, the recommended duration of treatment is 5 years.

Use in special patient groups

Disorders of kidney function: dose adjustment in patients with mild to moderate renal failure is not required.

Dysfunction of the liver: dose adjustment in patients with mild liver failure is not required. There is no data on the use of anastrozole in patients with severe hepatic insufficiency or with severe renal insufficiency (creatinine clearance less than 20 ml / min).

Children: Safety and efficacy in children not established.

Side effects:

In clinical trials and post-marketing experience with anastrozole, the following adverse reactions were observed (the reaction rate is defined as follows: very often (> 1/10), often (> 1/100 <1/10), infrequently (> 1/1000 <1 / 100), rarely (> 1/10000 <1/1000),very rarely (<1/10000, including individual messages):

Violations from the vessels: very often - "hot flashes", increased blood pressure; often - thrombophlebitis, venous thrombosis, deep vein thromboembolism, cerebrovascular accident (stroke), angina pectoris, myocardial infarction.

Disorders from the musculoskeletal and connective tissue: very often - back pain, arthralgia / joint stiffness, arthritis, osteoporosis, fractures; often - pain in the bones, arthrosis, myalgia; infrequently - a trigger finger.

Violations from the genitals and mammary glands: often - dryness of the vaginal mucosa, vaginal bleeding (mainly during the first weeks after cancellation or change of previous hormonal therapy on anastrozole), leukorrhea, pain in the area of the mammary glands, vaginitis, vulvovaginitis.

Disturbances from the skin and subcutaneous tissues: very often - skin rash; often thinning hair (alopecia), allergic reactions, increased sweating, itching; infrequently - hives; rarely - erythema multiforme, anaphylactoid reaction, skin vasculitis (including individual cases of purpura (Shenlaine-Henoch syndrome)); very rarely - Stevens-Johnson syndrome, angioedema.

Disorders from the gastrointestinal tract: very often - nausea; often - diarrhea, vomiting, abdominal pain, constipation, dyspepsia, dryness of the oral mucosa.

Disorders from the liver and bile ducts: often - increased activity of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, infrequently - increased activity of gamma-glutamyl transferase and bilirubin concentration, hepatitis.

Violations from the nervous system: very often - headache, depression, insomnia; often - dizziness, anxiety, paresthesia, drowsiness, nervousness, carpal tunnel syndrome (mainly observed in patients with risk factors of the disease), disorientation.

Disorders from the metabolism and nutrition: very often - peripheral edema; often - anorexia, weight gain, weight loss, hypercholesterolemia. Admission of the drug can cause a decrease in bone mineral density due to a decrease in the concentration of circulating estradiol, thereby increasing the risk of osteoporosis and bone fractures; infrequently - hypercalcemia (with or without increasing the concentration of parathyroid hormone).

General disorders and disorders at the injection site: very often - asthenia of mild or moderate severity, pain; often - flu-like syndrome, pain in the chest, pelvic pain, neck pain, fever.

Disturbances from the blood and lymphatic system: very often - lymphatic edema; often anemia, leukopenia.

Disturbances from the respiratory system, chest and mediastinum: very often - pharyngitis; often - cough, dyspnea, sinusitis, bronchitis, rhinitis.

Disorders from the side of the organ of vision: often - cataract.

Disorders from the kidneys and urinary tract: often - urinary tract infections.

Trauma, intoxication and complications of manipulation: often - accidental injuries.

Overdose:

Single clinical cases of accidental drug overdose are described. A single dose of anastrozole, which could lead to symptoms threatening life, is not established. Specific antidote does not exist, in case of an overdose, treatment should be symptomatic. You can induce vomiting if the patient is conscious. Dialysis may be performed.General supportive therapy, patient monitoring and monitoring of the function of vital organs and systems are recommended.

Interaction:

Studies on the drug interaction with phenazone and cimetidine indicate that the combined use of anastrozole with other drugs is unlikely to lead to a clinically significant drug interaction mediated by cytochrome P450.

Clinically significant drug interaction with the administration of anastrozole concomitantly with other commonly used drugs is absent.

At the moment there is no information on the use of anastrozole in combination with other antitumor drugs.

Preparations containing estrogens, reduce the pharmacological effect of anastrozole, and therefore, they should not be used simultaneously with anastrozole.

Do not use tamoxifen simultaneously with anastrozole, since it can weaken the pharmacological action of the latter.

Special instructions:

In women with a receptor-negative tumor to estrogens, the efficacy of anastrozole has not been demonstrated, unless there has been a previous positive clinical response to tamoxifen.

In case of doubt in the hormonal status of the patient, menopause should be confirmed by determining the sex hormones in the blood serum.

In the case of persisting uterine bleeding against the background of receiving anastrozole, consultation and supervision of the gynecologist is necessary.

Preparations containing estrogens should not be administered simultaneously with anastrozole, since these drugs will neutralize its pharmacological action.

Reducing the concentration of circulating estradiol, anastrozole can cause a decrease in bone mineral density with a subsequent increase in the risk of fracture. Patients with such a high risk should be treated according to the guidelines for the therapy of these complications.

In patients with osteoporosis or the risk of developing osteoporosis, bone mineral density should be assessed by densitometry, for example, DEXA-crawling (Dual-Energy X-ray Absorptiometry - dual-energy X-ray absorptiometry), at the beginning of treatment and in dynamics. If necessary, treatment or prevention of osteoporosis should be initiated, under the close supervision of a physician.

There is no data on the simultaneous use of anastrozole and analogues of LHRH (releasing hormone luteinizing hormone).

It is not known whether anastrozole results of treatment when used in conjunction with chemotherapy.

Safety data for prolonged treatment with anastrozole have not yet been obtained. When anastrozole is used more often than with tamoxifen, there are ischemic diseases, but the statistical significance is not noted.

The efficacy and safety of anastrozole and tamoxifen in their simultaneous application, regardless of the status of the hormonal receptors, are comparable to those of a single tamoxifen. The exact mechanism of this phenomenon is not yet known.

There is no data on the use of anastrozole in patients with severe liver function impairment.

Effect on the ability to drive transp. cf. and fur:

Some side effects of anastrozole, such as asthenia and drowsiness, can adversely affect the ability to perform potentially hazardous activities requiring increased concentration, attention and speed of psychomotor reactions. In this regard, when these symptoms appear, one should refrain from performing these activities.

Form release / dosage:

Tablets, film-coated, 1 mg each.

Packaging:For 10 or 14 tablets in a contour mesh package.2 contour packs of 14 tablets each, or 3 contour packs of 10 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

In dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:5 years. Do not take it beyond the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002150

Date of registration:17.07.2013

The owner of the registration certificate:BIOCAD, CJSC BIOCAD, CJSC Russia

Manufacturer: & nbsp

BIOCAD, CJSC Russia

Information update date: & nbsp26.12.2014

Illustrated instructions

Instructions

Anastrozole (Anastrozole)