Anastrozole tablets p / o 1mg, No. 30

• 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 progressing after tamoxifen treatment in postmenopausal women.

Inside, the tablet is swallowed whole with water. Application at the same time is recommended.
Adults, including the elderly: 1 mg 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.
In case of impaired renal function of a mild to moderate degree, dose adjustment is not required.
In case of mild liver dysfunction, dose adjustment is not required.

active substance: anastrozole - 1 mg;
excipients - sodium carboxymethyl starch (type A), povidone K-25, calcium stearate, sodium lauryl sulfate, lactose monohydrate; opadry II white (85 F);
shell composition (opadry II white (85 F)): polyvinyl alcohol, partially hydrolyzed, macrogol (polyethylene glycol), talc, titanium dioxide.

• Hypersensitivity to anastrozole or other components of the drug.

• Pregnancy and lactation period;

• Contraindicated in premenopausal women.

• Severe renal failure (creatinine clearance less than 20 ml / min).

• Moderate or 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 has not been established).

Carefully

Osteoporosis, hypercholesterolemia, ischemic heart disease, abnormal liver function, lactase deficiency, glucose-galactose malabsorption.

Trade name:

anastrozole.

International non-proprietary name:

anastrozole.

Dosage form:

film-coated tablets.

Composition for one tablet:

active substance: anastrozole - 1 mg;
excipients - sodium carboxymethyl starch (type A), povidone K-25, calcium stearate, sodium lauryl sulfate, lactose monohydrate; opadry II white (85 F);
shell composition (opadry II white (85 F)): polyvinyl alcohol, partially hydrolyzed, macrogol (polyethylene glycol), talc, titanium dioxide.

Description:

film-coated tablets, white or almost white, round, biconvex. The roughness of the film coating is allowed on the surface of the tablets.

Pharmacotherapeutic group:

antineoplastic agent - an estrogen synthesis inhibitor.

ATX code:

L02BG03.

Pharmacological properties

Pharmacodynamics
Anastrozole is a highly selective non-steroidal inhibitor of the aromatase enzyme, which in the body of postmenopausal women converts androstenedione in peripheral tissues into estrone and then into estradiol. The therapeutic effect in breast cancer patients is achieved by reducing the level of circulating estradiol. In postmenopausal women, anastrozole in a daily dose of 1 mg causes a decrease in estradiol levels by 80%.
It has no progestogenic, androgenic and estrogenic activity. A daily dose of up to 10 mg has no effect on the secretion of cortisol and aldosterone. No corticosteroid replacement is required. Anastrozole can cause a decrease in bone mineral density in patients with hormone-positive early postmenopausal breast cancer. Anastrozole alone, as well as in combination with bisphosphonates, does not alter plasma lipid levels.
Pharmacokinetics
It is rapidly absorbed, the maximum plasma concentration is reached within 2 hours after ingestion on an empty stomach. Food slightly reduces the rate of absorption. The degree of reduction has no clinically significant effect on the equilibrium plasma concentration of the drug with a single daily dose. Approximately 90-95% of the equilibrium concentration of anastrozole is achieved after 7 days of taking the drug. There is no information on the dependence of pharmacokinetic parameters on time and dose. The age of postmenopausal women does not affect pharmacokinetics. Communication with plasma proteins - 40%.
Anastrozole is excreted slowly from the body. The plasma half-life is 40-50 hours. Extensively metabolized in postmenopausal women. Unchanged, 10% of the dose is excreted in the urine within 72 hours after administration. Metabolized by N-dealkylation, hydroxylation and glucuronidation. The main metabolite, triazole, is inactive. Excretion of metabolites occurs in the urine.
Liver cirrhosis or impaired renal function does not alter the clearance of anastrozole after oral administration.
The pharmacokinetics of anastrozole in children has not been studied.

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 progressing after tamoxifen treatment in postmenopausal women.

Contraindications

• Hypersensitivity to anastrozole or other components of the drug.

• Pregnancy and lactation period;

• Contraindicated in premenopausal women.

• Severe renal failure (creatinine clearance less than 20 ml / min).

• Moderate or 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 has not been established).

Carefully

Osteoporosis, hypercholesterolemia, ischemic heart disease, abnormal liver function, lactase deficiency, glucose-galactose malabsorption.

Application during pregnancy and during breastfeeding

Use during pregnancy and breastfeeding is contraindicated.

Method of administration and dosage

Inside, the tablet is swallowed whole with water. Application at the same time is recommended.
Adults, including the elderly: 1 mg 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.
In case of impaired renal function of a mild to moderate degree, dose adjustment is not required.
In case of mild liver dysfunction, dose adjustment is not required.

Side effect

The incidence of side effects is given in the following gradation: very often (? 1/10); often (? 1/100, <1/10); infrequently (? 1/1000, <1/100); rarely (? 1/10000, <1/1000); very rare (<1/10000), including isolated messages.
From the side of the cardiovascular system: very often - hot flashes.
From the musculoskeletal system: very often - arthralgia, joint stiffness, arthritis; often - bone pain; infrequently - trigger finger.
On the part of the reproductive system: often - dryness of the vaginal mucosa, vaginal bleeding (mainly during the first weeks after canceling or changing the previous hormone therapy to anastrozole).
From the side of the skin:very often - skin rash; often - thinning hair, alopecia, allergic reactions; infrequently - urticaria; rarely - erythema multiforme, anaphylactoid reaction, cutaneous vasculitis (including isolated cases of purpura (Schonlein-Henoch syndrome)); very rarely - Stevens-Johnson syndrome, angioedema.
From the digestive system: very often - nausea; often - diarrhea, vomiting.
From the hepatobiliary system: often - increased activity of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase; infrequently - an increase in the activity of gamma-glutamyltransferase and the concentration of bilirubin, 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).
From the side of metabolism: often - anorexia, hypercholesterolemia; infrequently - hypercalcemia (with / without an increase in 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.
Others: 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.

Overdose

Overdose cases are isolated and accidental. A single dose of the drug that could lead to life-threatening symptoms has not been established.
Treatment: there is no specific antidote. Treatment is symptomatic. Induction of vomiting (if the patient is conscious). Dialysis. General supportive therapy, monitoring the patient and monitoring the function of vital organs and systems.

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 anastrozole at the same time as other commonly prescribed drugs. At the moment, there is no information on the use of anastrozole in combination with other anticancer drugs. Preparations containing estrogens reduce the pharmacological action of anastrozole, and therefore, they should not be administered concurrently with anastrozole. Tamoxifen should not be administered concurrently with anastrozole, as it can weaken the pharmacological effect of the latter.

special instructions

Safety and efficacy in children has not been established.
In women with estrogen receptor-negative tumors, the efficacy of anastrozole has not been demonstrated unless there has been a prior 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 the drug in patients with severe hepatic insufficiency and in patients with severe renal insufficiency (creatinine clearance less than 20 ml / min).
In the case of persisting uterine bleeding while taking anastrozole, consultation and supervision of a gynecologist is necessary.
Estrogen-containing drugs should not be administered concurrently.
A decrease in circulating estradiol levels can cause a decrease in bone mineral density with a consequent increase in the risk of fracture. Patients at such a high risk should be treated according to the guidelines for the management of these complications. The combined use of bisphosphonates in patients with an average and high risk of fractures helps prevent changes in the skeletal system. Supportive treatment with vitamin D and calcium in low-risk patients prevents changes in bone structure.
In patients with osteoporosis or at risk of developing osteoporosis, bone mineral density should be assessed using densitometry, for example, DEXA scanning (Dual-Energy X-ray Absorptiometry), at the beginning of treatment and over time. 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 drugs-analogues of luteinizing hormone-releasing hormone. It is not known whether anastrozole improves treatment outcomes when used with chemotherapy.
There are no safety data for long-term treatment with anastrozole.
With the use of anastrozole, ischemic diseases were observed more often than with tamoxifen therapy, 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 still unknown.

Influence on the ability to drive vehicles, mechanisms

Care should be taken when driving vehicles and potentially dangerous machinery, since anastrozole can cause asthenia and drowsiness.

Release form

Film-coated tablets 1 mg.
10 tablets in a blister made of polyvinyl chloride film and aluminum foil. One or three blister packs, together with instructions for use, are placed in a cardboard box.

Storage conditions

Store in a protected light place at a temperature not exceeding 25 ? C.
Keep out of the reach of children.

Shelf life

2 years.
Do not use after the expiration date printed on the package.

Vacation conditions

On prescription.

Name and address of the legal entity in whose name the registration certificate was issued / Organization accepting consumer claims

RUE 'Belmedpreparaty', Republic of Belarus
220007, Minsk, st. Fabricius, 30,

Manufacturer

RUE 'Belmedpreparaty'
Address of the place of production:
Republic of Belarus, 220006 Minsk, st. Mayakovsky, 1/5.