Anastrozole

Package leaflet (information for patients)

Tradename
Anastrozole

Dosage form
Tablets 1 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Anastrozole 1 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Antiestrogens

Pharmacological properties
Pharmacodynamics. Anastrozole is a highly selective non-steroidal aromatase inhibitor, an enzyme that converts androstenedione in the peripheral tissues into estrone and then into estradiol in postmenopausal women. Decreasing circulating concentrations of estradiol has been shown to have a beneficial effect in women with breast cancer. In postmenopausal women, anastrozole in a daily dose of 1 mg causes a decrease in estradiol levels by 80%. Anastrozole has no progestogenic, 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, when it is prescribed, replacement administration of corticosteroids is not required. Pharmacokinetics. The absorption of anastrozole is fast, the maximum plasma concentration is achieved 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 intake of a daily dose of anastrozole. After a seven-day intake of the drug, approximately 90-95% of the equilibrium concentration of anastrazole in blood plasma is achieved. There is no information on the dependence of the pharmacokinetic parameters of anastrozole on time or dose. The pharmacokinetics of anastrozole does not depend on the age of postmenopausal women. Communication with blood plasma proteins -40%. Anastrozole is excreted slowly, the half-life from plasma is 40-50 hours. Extensively metabolized in postmenopausal women. Less than 10% of the dose taken is excreted by the kidneys unchanged within 72 hours after taking the drug. Anastrozole metabolism occurs through the stages of N- dealkylation, hydroxylation and glucuronidation. Triazole, the main plasma metabolite of anastrozole, does not inhibit aromatase. Metabolites are excreted mainly by the kidneys. The clearance of anastrozole after oral administration in liver cirrhosis or renal dysfunction does not change.

Indications for use
Adjuvant therapy of early breast cancer with positive hormone receptors in postmenopausal women, including after adjuvant therapy with tamoxifen for 2-3 years. First line therapy for locally advanced or metastatic breast cancer, with positive or unknown hormone receptors in postmenopausal women. Second-line therapy for advanced breast cancer that progresses after tamoxifen treatment in postmenopausal women

Method of administration and dosage
Inside. The tablet is swallowed whole with water. It is recommended to take the drug at the same time, regardless of the meal. Adults, including the elderly: 1 mg orally 1 time per 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. Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment. Liver dysfunction: No dose adjustment is required in patients with mild to moderate hepatic dysfunction.

Side effects
The frequency of the adverse reactions listed below was determined according to the following criteria: very often (at least 1/10); often (more than 1/100, less than 1/10); sometimes (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rarely (less than 1/10000), including individual messages. From the side of the vessels: very often - "hot flushes" of blood to the face. Musculoskeletal and connective tissue disorders: very often - arthralgia / joint stiffness, arthritis; often - bone pain, myalgia; infrequently - trigger finger. On the part of the genitals and mammary gland: often - dryness of the vaginal mucosa, vaginal bleeding (mainly during the first weeks after canceling or changing the previous hormone therapy to anastrozole). On the part of the skin and subcutaneous tissues: very often - skin rash; often - thinning hair, alopecia, allergic reactions; infrequently - urticaria; rarely - erythema multiforme, anaphylactoid reaction, cutaneous vasculitis (including isolated cases of purpura (Shenlein-Henoch syndrome)), very rarely - Stevens- Johnson syndrome, angioedema. From the gastrointestinal tract: very often - nausea; often - diarrhea, vomiting. From the liver and biliary tract: often - increased activity of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase ; infrequently - increased activity of gamma- glutamyltransferase and bilirubin concentration, hepatitis. From the nervous system: very often - headache; often - drowsiness, carpal tunnel syndrome (mainly observed in patients with risk factors for this disease), sensitivity disorders (including paresthesia, loss or perversion of taste sensations). From the side of metabolism and nutrition: often - anorexia, hypercholesterolemia ; infrequently - hypercalcemia (with / without increasing the concentration of parathyroid hormone). Taking 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. General disorders: very often - mild to moderate asthenia. Adverse events noted in clinical trials not associated with taking anastrozole : anemia, constipation, dyspepsia, back pain, abdominal pain, increased blood pressure, weight gain, depression, insomnia, dizziness, anxiety, paresthesia

Contraindication
Hypersensitivity to anastrozole or other components of the drug; pregnancy and lactation; premenopausal period; severe hepatic impairment (safety and efficacy have not been established); concomitant therapy with tamoxifen or drugs containing estrogens; children's age (safety and effectiveness in children have not been established). With care: osteoporosis, hypercholesterolemia, ischemic heart disease, impaired liver function, severe renal failure (creatinine clearance <20 ml / min), lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the dosage form of the drug contains lactose). Contraindicated in pregnancy. During treatment, breastfeeding should be discontinued.

Overdose
Isolated clinical cases of accidental drug overdose are described. A single dose of anastrozole that could lead to life-threatening symptoms has not been established. There is no specific antidote, in case of an overdose, treatment should be symptomatic. Treatment: vomiting can be induced if the patient is conscious. Dialysis can be done. General supportive therapy, observation of the patient and monitoring of the function of vital organs and systems are recommended.

Precautions
Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
Perform blood tests as directed by your doctor. Please consult your doctor.
This drug lowers the level of estrogen in your body, which can thin and weaken bones. This can increase the risk of bone fractures, such as fractures of the spine, hip, and wrist. Consult your doctor.
Get a bone density test as directed by your doctor. Consult your doctor.
Increases in cholesterol have been associated with this drug. If you have any questions, please consult your doctor.
This drug may cause fertility problems. This can negatively affect the ability to have children. Consult your doctor.
This drug may have adverse effects on the fetus. Before you start taking this drug, you will have a pregnancy test to make sure you are NOT pregnant.
During treatment and for some time after the last dose of this drug, women need to use contraception. Ask your doctor for how long to use contraception. If you become pregnant, contact your doctor immediately.

Interaction with other medicinal products
Studies on drug interactions with phenazone (Antipyrin) and cimetidine indicate that the combined use of anastrozole with other drugs is unlikely to lead to clinically significant drug interactions mediated by cytochrome P450. There is no clinically significant drug interaction when taking the drug Anastrozole simultaneously with other commonly prescribed drugs. At the moment, there is no information on the use of the drug in combination with other antineoplastic drugs. Preparations containing estrogens reduce the pharmacological action of anastrozole, and therefore, they should not be prescribed simultaneously with it. Do not assign tamoxifen concurrently with anastrozole, as it may weaken the pharmacological action of the latter.

Special instructions
Safety and effectiveness in children have not been established. Women with retseptorootritsatelnoy tumor estrogen efficacy of anastrozole has not been demonstrated, except in cases where there was a previous positive clinical response to tamoxifen. In case of doubt about the hormonal status of the patient, menopause should be confirmed by the determination of sex hormones in the blood serum. There is no data on the use of anastrozole in patients with severe liver dysfunction. In the case of persisting uterine bleeding while taking anastrozole, consultation and supervision of a gynecologist is necessary. In patients with osteoporosis or at increased risk of developing osteoporosis, bone mineral density should be assessed using densitometry, such as DEXA (dual energy X - ray absorptiometry), at the beginning of treatment and regularly throughout the course. If necessary, treatment or prevention of osteoporosis should be prescribed and the patient's condition should be carefully monitored. Since anastrozole reduces the concentration of circulating estradiol, it 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 of bone mineral density caused by anastrozole or their benefits when used for prophylaxis. There is no data on the simultaneous use of anastrozole and LHRH analog drugs (luteinizing hormone- releasing hormone). It is not known whether anastrozole improves treatment outcomes when used with chemotherapy. Safety data for long-term treatment with anastrozole have not yet been obtained. With the use of anastrozole more often than with tamoxifen therapy, ischemic diseases were observed, however, no statistical significance was noted. The efficacy and safety of anastrozole and tamoxifen when used simultaneously, regardless of the status of hormonal receptors, are comparable to those when using tamoxifen alone. The exact mechanism of this phenomenon is not yet known. Impact on the ability to drive vehicles and operate machinery Some side effects of anastrozole (asthenia and drowsiness) can adversely affect the ability to drive vehicles and use machinery. Therefore, during the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Pregnancy and elbowing
Contraindicated in pregnancy. During treatment, breastfeeding should be discontinued.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
Anastrozole 1 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.