Anastrex (Tablets) Instructions for Use

Marketing Authorization Holder

Anstar, AG (Switzerland)

Manufactured By

Khandelwal Laboratories, Pvt. Ltd. (India)

ATC Code

L02BG03 (Anastrozole)

Active Substance

Anastrozole (Rec.INN registered by WHO)

Dosage Form

Anastrex

Film-coated tablets, 1 mg: 28 or 30 pcs.

Dosage Form, Packaging, and Composition

14 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Aromatase inhibitor

Pharmacotherapeutic Group

Antineoplastic agent, estrogen synthesis inhibitor

Pharmacological Action

Anastrozole is a highly selective nonsteroidal aromatase inhibitor – an enzyme by which androstenedione and testosterone are converted into estrone and estradiol, respectively, in tissues in 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. At 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

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 steady-state plasma concentration of anastrozole after a single daily dose.

After 7 days of drug administration, approximately 90-95% of the steady-state plasma concentration of anastrozole is achieved.

There is no information on the dependence of anastrozole pharmacokinetic parameters on time or dose. The pharmacokinetics of anastrozole do not depend on the age of postmenopausal women.

Plasma protein binding is 40%.

Anastrozole is extensively metabolized in postmenopausal women, with less than 10% excreted by the kidneys unchanged within 72 hours after drug administration.

The T_1/2 of anastrozole from plasma is 40-50 hours. The metabolism of anastrozole occurs via 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.

The clearance of anastrozole after oral administration does not change in cases of 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 or metastatic breast cancer with positive or unknown hormone receptor status in postmenopausal women;
• Second-line therapy of advanced breast cancer progressing after prior tamoxifen therapy.

ICD codes

Dosage Regimen

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: 1 mg orally once daily 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.

Renal impairment: dose adjustment is not required in patients with impaired renal function.

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

Adverse Reactions

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

Cardiovascular system: very common – hot flushes.

Musculoskeletal system: very common — arthralgia; rare — trigger finger.

Reproductive system: common – vaginal dryness, vaginal bleeding (mainly during the first weeks after discontinuation or switching from prior hormonal therapy to Anastrozole).

Skin and skin appendages: very common – skin rash; common – hair thinning, alopecia; very rare – malignant exudative erythema (Stevens-Johnson syndrome).

Digestive system: very common — nausea; common – diarrhea, vomiting, anorexia.

Hepatobiliary system: common – increased ALT, AST, and ALP activity; rare — increased GGT activity and bilirubin concentration, hepatitis.

Nervous system: very common – headache; common — increased somnolence, carpal tunnel syndrome (mainly observed in patients with risk factors for this condition).

Metabolism: common – hypercholesterolemia. The drug may cause a decrease in bone mineral density due to the reduction 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

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

With caution: osteoporosis, hypercholesterolemia, coronary heart disease, hepatic impairment, severe renal failure (CrCl < 20 ml/min), lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the drug formulation contains lactose).

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment (safety and efficacy not established).

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

Use in Renal Impairment

With caution: severe renal failure (CrCl < 20 ml/min).

Pediatric Use

Contraindication: childhood (safety and efficacy in children not established)

Special Precautions

If there is 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 monitoring by a gynecologist are necessary.

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

Since Anastrozole reduces circulating estradiol concentration, this may lead to a decrease in bone mineral density.

Therefore, in patients with osteoporosis or at increased risk of developing osteoporosis, bone mineral density should be assessed by densitometry, for example, DEXA scanning (dual-energy X-ray absorptiometry) at the start of treatment and regularly during it.

If necessary, treatment or prevention of osteoporosis should be prescribed and the patient’s condition carefully monitored.

Currently, there is insufficient data regarding the positive effect of bisphosphonates on anastrozole-induced bone mineral density loss or their benefit for prevention.

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

In receptor-negative breast cancer or in case of prior tamoxifen therapy failure, the efficacy of anastrozole is quite low.

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

The efficacy and safety of anastrozole and tamoxifen when used concomitantly, 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 side effects of anastrozole, such as asthenia and somnolence, may adversely affect the ability to perform potentially hazardous activities requiring 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 cases of accidental drug overdose have been 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 overdose, treatment should be symptomatic. Vomiting may 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

Drug interaction studies with phenazone and cimetidine indicate that the concomitant use of anastrozole with other drugs is unlikely to lead to clinically significant drug interactions mediated by cytochrome P450.

Currently, there is no information on the use of anastrozole in combination with other anticancer drugs.

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

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

Storage Conditions

Store in a dry place, out of reach of children, at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 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.