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

Excipients (core): lactose monohydrate (sugar milk) - 72.0 mg, microcrystalline cellulose - 15.6 mg, povidone (polyvinylpyrrolidone) 3.0 mg, magnesium stearate 0.9 mg, silicon colloidal dioxide 0.5 mg, sodium carboxymethyl starch - 2.0 mg.

Auxiliary substances (shell): hypromellose - 1.65 mg, macrogol-4000 - 0.45 mg, titanium dioxide - 0.90 mg.

Description:tablets are round biconvex, covered with a film shell of white or almost white color, on the fracture are visible two layers - a core of white or almost white color and a film membrane.

Pharmacotherapeutic group:antitumor agent, estrogen synthesis inhibitor.

ATX: & nbsp

L.02.B.G Enzyme Inhibitors

L.02.B.G.03 Anastrozole

Pharmacodynamics:

Anastrozole is a highly selective non-steroidal 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. Reduction of circulating concentrations Estradiol, as it turned out, has a positive effect on women with breast cancer glands. In postmenopausal women anastrozole in a daily dose of 1 mg causes a decrease concentration of estradiol by 80%.

Anastrozole does not have progestogen, androgenic or estrogenic activity.Regular intake of daily doses of anastrozole up to 10 mg does not affect the secretion of cortisol or aldosterone, therefore, it does not require the substitution of corticosteroids for its administration.

Pharmacokinetics:

Absorption of anastrozole is fast, the maximum concentration in the plasma is reached within two hours after ingestion (on an empty stomach). 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 anastrozole in plasma with a single daily intake of anastrozole. After seven days of taking the drug, approximately 90-95% of the equilibrium concentration of anastrozole in the blood plasma is reached. 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. 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Anastrozole is withdrawn slowly, the half-life from the plasma is 40-50 hours.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 taken is excreted by the kidneys unchanged for 72 hours after taking the drug.Anastrozole metabolism occurs through stages N-dealkylation, hydroxylation and glucuronidation. Triazole, the main metabolite of anastrozole in plasma, does not inhibit aromatase. Metabolites are excreted mainly by the kidneys.

The clearance of anastrozole after oral administration with liver cirrhosis or renal dysfunction does not change.

Indications:

Adjuvant therapy for early hormone-positive breast cancer in postmenopausal women;

Treatment of advanced breast cancer in postmenopausal women;

Adjuvant therapy for early hormone-positive breast cancer in postmenopausal women after tamoxifen therapy for 2-3 years.

Contraindications:

Hypersensitivity to anastrozole or other components of the drug;

Pregnancy and the period of breastfeeding;

The Premenopausal Period;

Severe renal failure (creatinine clearance <20 mL / min);

The average degree of hepatic insufficiency;

Severe hepatic insufficiency (safety and efficacy not established);

Concomitant therapy with tamoxifen or preparations containing estrogens;

Children under 18 years of age (safety and efficacy in children not established).

Carefully:

osteoporosis, hypercholesterolemia, ischemic heart disease, impaired liver function, lactase deficiency, lactose intolerance, glucose-galactose malabsorption (in the drug form of the drug contains lactose).

Pregnancy and lactation:

Contraindicated in pregnancy. For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside. The tablet is swallowed whole, washed down with water. It is recommended to take the drug at the same time, regardless of food intake.

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.

Light and moderate degree of renal failure: dose adjustment in patients with mild and moderate renal dysfunction is not required.

An easy degree of hepatic insufficiency: dose adjustment in patients with mild liver failure is not required.

Side effects:

Vascular disorders: "tides" of blood to the face, increased blood pressure.

Disorders from the musculoskeletal and connective tissues: arthralgia / joint stiffness, arthritis; pain in bones and muscles, trigger finger.

Disorders from the urogenital system: urinary tract infections, vulvovaginitis, dryness of the vaginal mucosa, vaginal bleeding (in mainly during the first weeks after the cancellation or change of previous hormone therapy anastrozole).

Disturbances from the skin and subcutaneous tissues: skin rash, thinning of hair, sweating, alopecia; allergic reactions: urticaria, erythema multiforme, anaphylactoid reaction, skin vasculitis (including isolated cases of purpura (Shenllein-Genoch syndrome), Stevens-Johnson syndrome, angioedema.

Disorders from the gastrointestinal tract: nausea, diarrhea, vomiting, constipation, indigestion, gastrointestinal disorders.

Violations from the blood and lymphatic system: anemia, lymphedema, venous thromboembolism.

Disturbances from the respiratory system, chest and mediastinal organs: pharyngitis, dyspnea, sinusitis, bronchitis.

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

From the hepatobiliary system: increased activity of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, increased activity of gamma-glutamyltransferase and bilirubin concentration, hepatitis.

Impaired nervous system: headache, drowsiness, depression, insomnia, dizziness, anxiety, paresthesia, carpal tunnel syndrome (mainly observed in patients with risk factors of the disease).

Disorders from the metabolism and nutrition: anorexia, hypercholesterolemia, weight gain, hypercalcemia (with / without increasing the concentration of parathyroid hormone). Admission of the drug may 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.

Other: asthenia, back pain, abdominal pain, chest pain, the emergence of secondary infections, flu-like syndrome, neoplasms.

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.

Treatment: it is possible to 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 drug interaction with phenazone (Antipyrine) and cimetidine indicate that the combined use of anastrozole with other drugs is unlikely to lead to clinically significant drug interaction, mediated by cytochrome P450.

Clinically significant drug interaction when taking the drug Anastrozole simultaneously with other commonly prescribed drugs is absent.

At the moment there is no information about the use of the drug Anastrozole in combination with other antitumor drugs.

Preparations containing estrogens reduce the pharmacological action of anastrozole, so they should not be administered simultaneously.

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

Special instructions:

Safety and efficacy in children are not established.

In women with a receptor-negative tumor to estrogens, the efficacy of anastrozole has not been demonstrated, except in cases where there was a previous positive clinical response to tamoxifen. In case of doubt in the hormonal status of the patient, menopause should be confirmed by the determination of sex hormones in the blood serum.

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

There is no data on the use of anastrozole in patients with moderate to severe hepatic impairment.

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

In patients with osteoporosis or an increased risk of osteoporosis, bone mineral density should be assessed by densitometry, for example, DEXA- scanning (dual-energy X-ray absorptiometry), at the beginning of treatment and regularly throughout its duration. If necessary, prescribe the treatment or prevention of osteoporosis and carefully monitor the patient's condition. Because the anastrozole reduces the concentration of circulating estradiol, this can lead to a decrease in bone mineral density. At the moment, there is insufficient data on the positive effect of bisphosphonates on the loss bone mineral density caused by anastrozole or their benefits when used for the purpose of prevention.

There is no evidence of simultaneous use of anastrozole and analogues of LHRH (luteinizing hormone releasing 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 was used more often than with tamoxifen, there were ischemic diseases, but no statistical significance was noted. Efficacy and safety of anastrozole and tamoxifen in their simultaneous application regardless of statushormonal receptors are comparable with those when using one tamoxifen. The exact mechanism of this phenomenon is not yet known.

Effect on the ability to drive transp. cf. and fur:Some side effects of anastrozole (asthenia, drowsiness, headache, dizziness) can adversely affect the ability to drive vehicles and control mechanisms. Therefore, during the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions. When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:

Tablets, film-coated 1 mg.

Packaging:

For 10, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50, 60, 100 or 120 tablets in cans of polymeric for medicines. One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002323

Date of registration:09.12.2013

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp09.12.2013

Illustrated instructions

Instructions

Anastrozole (Anastrozole)