Anastrozole-Teva (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Contact Information

TEVA (Israel)

ATC Code

L02BG03 (Anastrozole)

Active Substance

Anastrozole (Rec.INN registered by WHO)

Dosage Form

Anastrozole-Teva

Film-coated tablets, 1 mg: 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with an engraving “93” on one side and “A10” on the other.

Excipients: lactose monohydrate (200 mesh) – 64 mg, povidone K30 – 4 mg, spray-dried lactose monohydrate – 23 mg, sodium carboxymethyl starch type A – 7 mg, magnesium stearate – 1 mg.

Film coating composition Opadry white 02G28619 (hypromellose E464 – 1.875 mg, titanium dioxide E171 – 0.6375 mg, macrogol-6000 – 0.3 mg, macrogol-400 – 0.1875 mg).

7 pcs. – blisters (4) – cardboard packs.
7 pcs. – blisters (8) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Aromatase inhibitor

Pharmacotherapeutic Group

Antineoplastic hormonal agents and hormone antagonists; hormone antagonists and related compounds; aromatase inhibitors

Pharmacological Action

Antitumor drug, inhibitor of estrogen synthesis.

Anastrozole is a highly selective non-steroidal aromatase inhibitor – an enzyme by which androstenedione is converted to estrone and then to estradiol in peripheral tissues in postmenopausal women. The reduction in circulating estradiol concentration in patients with breast cancer has a therapeutic effect. In postmenopausal women, Anastrozole at a daily dose of 1 mg causes an 80% reduction in estradiol concentration.

Anastrozole has no progestogenic, androgenic, or estrogenic activity. In daily doses up to 10 mg, it does not affect the secretion of cortisol and aldosterone; therefore, corticosteroid replacement therapy is not required when using anastrozole.

Pharmacokinetics

Absorption and Distribution

After oral administration, Anastrozole is rapidly absorbed from the gastrointestinal tract. C_max in plasma is usually reached within 2 hours after oral administration (on an empty stomach). Food slightly reduces the rate of absorption but not its extent and does not lead to a clinically significant effect on the C_ss of the drug in plasma after a single daily dose of anastrozole.

After 7 days of drug administration, approximately 90-95% of the C_ss of anastrozole in plasma is achieved. There is no information on the dependence of the pharmacokinetic parameters of anastrozole on time or dose. Plasma protein binding is 40%.

Metabolism and Excretion

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

Pharmacokinetics in Special Clinical Cases

The pharmacokinetics of anastrozole do not depend on the age of postmenopausal women.

The clearance of anastrozole after oral administration does not change in liver cirrhosis or impaired renal function.

Indications

• Adjuvant therapy of early hormone receptor-positive breast cancer in postmenopausal women;
• First-line therapy of locally advanced breast cancer with positive or unknown hormone receptors in postmenopausal women;
• Second-line therapy of advanced breast cancer progressing after tamoxifen treatment.

ICD codes

Dosage Regimen

The drug is taken orally. 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, are prescribed 1 mg orally once/day for a long duration. If signs of disease progression appear, the drug should be discontinued. For adjuvant therapy, the recommended duration of treatment is 5 years.

In case of impaired renal function, dose adjustment is not required.

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

Adverse Reactions

The frequency of adverse reactions listed below was determined according to the following criteria: very common (≥ 1/10), common (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (> 1/10,000, < 1/1000); very rare (< 1/10,000), including isolated reports.

From the cardiovascular system: very common – hot flushes.

From the musculoskeletal system: very common – arthralgia; rare – trigger finger.

From the reproductive system: common – vaginal dryness, vaginal bleeding (mainly during the first weeks after discontinuation or replacement of previous hormonal therapy with Anastrozole).

Dermatological reactions: very common – skin rash; common – hair thinning, alopecia; very rare – erythema multiforme (Stevens-Johnson syndrome).

From the digestive system: very common – nausea; common – diarrhea, vomiting, anorexia.

From the hepatobiliary system: increased activity of ALT, AST, and ALP; rare – increased activity of GGT and bilirubin concentration, hepatitis.

From the nervous system: very common – headache; common – increased drowsiness, carpal tunnel syndrome (mainly observed in patients with risk factors for this condition).

From metabolism: common – hypercholesterolemia. Taking the drug may cause a decrease in bone mineral density due to a decrease in circulating estradiol concentration, thereby increasing the risk of osteoporosis and bone fractures.

Allergic reactions: common – allergic reactions; very rare – anaphylactoid reactions, angioedema, urticaria, anaphylactic shock.

Other: very common – asthenia.

Contraindications

• Premenopausal period;
• Severe hepatic insufficiency (safety and efficacy not established);
• Concomitant therapy with tamoxifen or drugs containing estrogens;
• Pregnancy;
• Period of lactation (breastfeeding);
• Childhood (safety and efficacy in children not established);
• Hypersensitivity to anastrozole or other components of the drug.

With caution the drug should be prescribed for osteoporosis, hypercholesterolemia, coronary artery disease, impaired liver function, severe renal failure (creatinine clearance <20 ml/min), lactase deficiency, lactose intolerance, glucose/galactose malabsorption (the drug formulation contains lactose).

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

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

The use of the drug is contraindicated in severe hepatic insufficiency (safety and efficacy not established).

Use in Renal Impairment

In case of impaired renal function, dose adjustment is not required.

Pediatric Use

Safety and efficacy in children have not been established, use is contraindicated.

Special Precautions

In case of doubt about the patient’s hormonal status, menopause should be confirmed by determining the concentration of sex hormones in the blood serum. In case of persistent uterine bleeding while taking anastrozole, consultation and observation by a gynecologist are necessary.

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

In patients with osteoporosis or at 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 during it. If necessary, treatment or prevention of osteoporosis should be prescribed and the patient’s condition should be carefully monitored. Since Anastrozole reduces circulating estradiol concentration, this may lead to a decrease in bone mineral density. To date, there is insufficient data regarding the positive effect of bisphosphonates on bone mineral density loss caused by anastrozole or their benefit for prophylactic use.

There are no data on the simultaneous use of anastrozole and GnRH analogue drugs.

In women with estrogen receptor-negative tumors, the efficacy of anastrozole has not been demonstrated, except in cases where there was a prior positive clinical response to tamoxifen.

Drugs containing estrogens should not be prescribed simultaneously with anastrozole, as these drugs will negate its pharmacological action.

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

It is not known whether Anastrozole improves treatment outcomes when used in combination with chemotherapy.

Effect on ability to drive vehicles and operate machinery

Some adverse reactions of anastrozole, such as asthenia and drowsiness, may adversely affect the ability to perform potentially hazardous activities that require increased concentration and speed of psychomotor reactions. In this regard, it is recommended to exercise caution when driving vehicles and operating machinery if these symptoms occur.

Overdose

Isolated clinical cases of accidental drug overdose have been described. A single dose of anastrozole that could lead to life-threatening symptoms has not been established.

Treatment there is no specific antidote; in case of overdose, symptomatic therapy is carried out. Vomiting can be induced if the patient is conscious. Dialysis may be performed. General supportive therapy, patient monitoring, and control of vital organ functions are recommended.

Drug Interactions

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

There is no clinically significant drug interaction when taking anastrozole simultaneously with other frequently prescribed drugs.

To date, there is no information on the use of anastrozole in combination with other antitumor drugs.

Drugs containing estrogens reduce the pharmacological action of anastrozole, and therefore they should not be prescribed simultaneously with anastrozole.

Tamoxifen should not be prescribed simultaneously with anastrozole as it may weaken the pharmacological action of the latter.

Storage Conditions

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.