Anastrozol-Teva, 1 mg 28 pcs

Pharmacodynamics

Anastrozole is an antitumor drug, an inhibitor of estrogen synthesis.

Anastrozole is a highly selective nonsteroidal aromatase inhibitor, an enzyme by which, in postmenopausal women, androstenedione is converted in peripheral tissues to estrone and then to estradiol. Reducing the concentration of circulating estradiol in patients with breast cancer has a therapeutic effect. In postmenopausal women, anastrozole at a daily dose of 1 mg causes a decrease in estradiol concentrations by 80%.

Anastrozole has no gestagenic, androgenic and estrogenic activity. In daily doses up to 10 mg it has no effect on cortisol and aldosterone secretion, therefore, corticosteroid replacement administration is not required when using anastrozole.

Pharmacokinetics

Intake and distribution

Anastrozole is rapidly absorbed from the gastrointestinal tract after oral administration. C_max in plasma is usually reached within 2 h after oral administration (fasting). Food slightly reduces the rate of absorption but not its degree and does not result in a clinically significant effect on plasma C_ss of the drug in a single daily dose of anastrozole.

After 7 days of administration, approximately 90-95% of the plasma C_ss of anastrozole is achieved. There are no data on the time or dose dependence of the pharmacokinetic parameters of anastrozole. Binding to plasma proteins is 40%.

Metabolism and excretion

Anastrozole is extensively metabolized in postmenopausal women, with less than 10% excreted unchanged by the kidneys within 72 hours after drug administration. T_1/2 of anastrozole from blood plasma is 40-50 h. Metabolism of anastrozole is by N-dealkylation, hydroxylation and glucuronidation. Metabolites of anastrozole are excreted mainly by the kidneys. The main metabolite of anastrozole is triazole, which is determined in blood plasma, has no pharmacological activity.

Pharmacokinetics in special clinical cases

The pharmacokinetics of anastrozole are independent of age in postmenopausal women.

The clearance of anastrozole after oral administration is not altered in cirrhosis or impaired renal function.

Indications

Breast Cancer

Adjuvant therapy for early hormone receptor-positive breast cancer 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 advanced breast cancer after tamoxifen treatment in postmenopausal women.
  

Active ingredient

Anastrozole

Composition

1 tablet contains: the active substance anastrozole 1.0 mg; excipients: lactose monohydrate (200 mesh) 64.0 mg, povidone-K30 4.0 mg, lactose monohydrate (spray dried) 23.0 mg, sodium carboxymethyl starch, type A 7,0 mg, magnesium stearate 1.0 mg, opadray white 02G28619 (hypromellose E464 1.8750 mg, titanium dioxide E171 0.6375 mg, macrogol-6000 0.3000 mg, macrogol-400 0.1875 mg).

How to take, the dosage

Ingestion. The tablet should be swallowed whole with water. It is recommended to take the drug at the same time regardless of meals.

Adults, including the elderly: 1 mg orally once daily for a long time. If there are signs of disease progression, the drug should be discontinued. As adjuvant therapy, the recommended duration of treatment is 5 years.

Kidney function disorders:Dose adjustment is not required in patients with impaired renal function.

Hepatic disorders:Dose adjustment in patients with mild to moderate hepatic impairment is not required.

Interaction

Studies on drug interactions with phenazone and cimetidine indicate that co-administration of anastrozole with other drugs is unlikely to result in clinically significant cytochrome P450-mediated drug interactions.

There are no clinically significant drug interactions when anastrozole is taken concomitantly with other commonly prescribed drugs.

There is currently no information about the use of anastrozole in combination with other anticancer drugs.

The drugs containing estrogens reduce the pharmacological effects of anastrozole, so they should not be prescribed concomitantly with anastrozole.

Tamoxifen should not be used at the same time as anastrozole, because it may decrease the pharmacologic effects of the latter.

Special Instructions

In case of doubts about a patient’s hormonal status, menopause should be confirmed by determining the concentration of sex hormones in the blood serum. If uterine bleeding persists while taking anastrozole, a gynecologist should be consulted and monitored.

There are no data on the use of anastrozole in patients with severe hepatic impairment.

In patients with osteoporosis or who are at increased risk of osteoporosis the bone mineral density should be assessed by densitometry, such as DEXA (dual-energy X-ray absorptiometry), at the start of treatment and regularly throughout treatment. Treatment or prophylaxis for osteoporosis should be prescribed as needed, and the patient’s condition should be closely monitored. Because anastrozole reduces circulating estradiol concentrations, it may lead to a decrease in bone mineral density. There are insufficient data to date regarding the beneficial effects of bisphosphonates on anastrozole-induced loss of bone mineral density or their benefit when used for prophylaxis.

There are no data on concomitant use of anastrozole and GnRH analogues.

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

Oestrogen-containing medications should not be administered concomitantly with anastrozole, because these medications would negate its pharmacological effect.

The efficacy and safety of anastrozole and tamoxifen when used concomitantly, regardless of hormone receptor status, is comparable to that of tamoxifen alone. The exact mechanism of this phenomenon is not yet known.

It is not known whether anastrozole improves treatment outcomes when used together with chemotherapy.

Impact on ability to drive vehicles and other mechanisms requiring high concentration

Some adverse reactions of anastrozole, such as asthenia and somnolence, may adversely affect the ability to perform potentially hazardous activities requiring high concentration and rapid psychomotor reactions. In this regard, it is recommended to exercise caution when driving vehicles and mechanisms in case of the appearance of these symptoms.

Synopsis

Round biconvex film-coated tablets, white or almost white, engraved “93” on one side and “A10” on the other.

Contraindications

• High sensitivity to anastrozole or other components

The drug.

• Premenopausal period.
• Developed hepatic insufficiency (safety and

Efficacy not established.)

• Companion therapy with tamoxifen or drugs containing estrogens.
  • Pregnancy and lactation.
  • Childhood (safety and effectiveness in children

  has not been established.)

  • Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

  Cautions

  Osteoporosis, hypercholesterolemia, coronary heart disease, hepatic impairment, severe renal failure (creatinine clearance less than 20 ml/min).

Side effects

The frequency of adverse reactions below was determined according to the following criteria: very common (at least 1/10); common (more than 1/100, less than 1/10), infrequent (more than 1/1000, less than 1/100), rare (more than 1/10000, less than 1/1000); very rare (less than 1/10000), including individual reports.

Vascular side: very often – “rushes” of blood to the face.

Skeletal, muscular and connective tissue: very common – arthralgia/joint stiffness, arthritis; frequent – bone pain, myalgia; infrequent – trigger finger.

On the genital and mammary glands: frequently – vaginal mucosal dryness, vaginal bleeding (mostly during the first weeks after withdrawal or change of prior hormone therapy to anastrozole).

Skin and subcutaneous tissue: very common – skin rash; common – thinning of hair, alopecia, allergic reactions; infrequent – urticaria; rare – erythema multiforme, anaphylactoid reaction, cutaneous vasculitis (including individual cases of purpura (Schoenlein-Genoch syndrome)); very rare – Stevens-Johnson syndrome, angioedema.

Gastrointestinal tract: very often – nausea; often – diarrhea, vomiting.

Hepatic and biliary tract disorders: often – increased activity of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase; infrequent – increased activity of gamma-glutamyl transferase and bilirubin concentration, hepatitis.

Nervous system disorders: very common – headache; common – somnolence, carpal tunnel syndrome (mainly observed in patients with risk factors for this disease), sensitivity disorders (including paresthesia, loss or perversion of taste).

Metabolism and nutrition:often – anorexia, hypercholesterolemia; infrequently – hypercalcemia (with/without increased concentration of parathormone). Administration of anastrozole may cause a decrease in bone mineral density due to a decrease in circulating estradiol concentrations, thereby increasing the risk of osteoporosis and bone fractures.

General disorders: very often mild to moderate asthenia.

Unwanted phenomena noted in clinical studies not related to anastrozole administration: anemia, constipation, dyspepsia, back pain, abdominal pain, increased blood pressure, weight gain, depression, insomnia, dizziness, anxiety, paresthesias.

Overdose

Single clinical cases of accidental overdose of the drug have been described. A single dose of anastrozole that could result in life-threatening symptoms has not been established. There is no specific antidote, in case of overdose treatment should be symptomatic. Vomiting may be induced if the patient is conscious. Dialysis may be performed. General supportive therapy, observation of the patient and control of functions of vital organs and systems are recommended.

Pregnancy use

The drug is contraindicated in pregnancy and lactation.