ANASTRAZOLE DENK 1

Indications

• Adjuvant treatment of estrogen-receptor-positive early invasive breast cancer in postmenopausal women
• Treatment of advanced breast cancer in postmenopausal women which is estrogen-receptor-positive or responsive to tamoxifen

Dosage

Adults: 1 mg orally once daily.

Mechanism of action

Anastrozole exerts its anti-estrogenic effects by selectively and competitively inhibiting the aromatase enzyme, predominantly found in the adrenal glands, liver, and fatty tissues. By blocking the conversion of androgens to estrogens, anastrozole effectively reduces circulating estrogen levels, which are crucial for the growth of hormone receptor-positive breast tumors.

Pharmacodynamics

Anastrozole leads to a significant reduction in serum estradiol concentrations, achieving approximately a 70% decrease within 24 hours of administration of 1 mg once daily. The effects of the drug can last for up to six days after discontinuation. Long-term use may affect bone mineral density, and patients with pre-existing ischemic heart disease should weigh the risks of therapy due to an observed increase in ischemic cardiovascular events.

Pharmacokinetics

Anastrozole is absorbed well after oral administration, with peak plasma concentrations typically occurring within 2 hours. It has a half-life of approximately 50 hours, allowing for once-daily dosing. The drug is extensively metabolized in the liver, primarily via cytochrome P450 enzymes, and is eliminated through urine. Caution is advised in patients with hepatic impairment as it may affect drug clearance.

Contra-indications

• Premenopausal women

Adverse effects

• Alopecia
• Decreased appetite
• Constipation
• Depression
• Dyspnoea
• Headache
• Insomnia
• Thromboembolism
• Endometrial changes
• Hyperplasia
• Uterine disorders
• Weight increased
• Anaemia
• Leukopenia
• Thrombocytopenia
• Hepatic disorders
• Uterine haemorrhage
• Vertigo
• Arthritis
• Asthenia
• Bone pain
• Carpal tunnel syndrome
• Diarrhoea
• Drowsiness
• Hot flush
• Hypercholesterolaemia
• Hypersensitivity
• Joint disorders
• Myalgia
• Nausea
• Osteoporosis
• Abnormal skin reactions
• Taste altered
• Vaginal haemorrhage
• Vomiting
• Vulvovaginal dryness

Interactions

• Tamoxifen - increased risk of thromboembolism
• Caution with hepatic impairment as it may decrease elimination

Precautions

• Consider monitoring bone mineral density in long-term therapy
• Evaluate risks in patients with pre-existing ischemic heart disease

Pregnancy

Avoid - possible effects on fetal development

Breast-feeding

Avoid - suppresses lactation

Storage

Store at room temperature, away from moisture and heat

Formulations

• Tablets - 1 mg

Mechanism of action

Anastrazole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues. Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone. In postmenopausal women, estrogen is primarily derived from the conversion of adrenally-produced androgens into estrogens by the aromatase enzyme - by competitively inhibiting the biosynthesis of estrogen at these enzymes, anastrozole effectively suppresses circulating estrogen levels and, subsequently, the growth of hormone receptor-positive tumours. Anastrozole is a nonsteroidal aromatase inhibitor that interferes with estradiol production in peripheral tissues. Adrenally generated androstenedione, the chief source of circulating estrogen in postmenopausal women, is converted by aromatase to estrone, which is further converted to estradiol. Growth of many breast cancer tumors containing estrogen receptors and aromatase can be promoted by estrogen. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. Because estrogen acts as a growth factor for hormone-dependent breast cancer cells, anastrozole-induced reduction of serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression. Anastrozole selectively inhibits the conversion of androgens to estrogens. In postmenopausal women, ovarian secretion of estrogen declines and conversion of adrenal androgens (mainly androstenedione and testosterone) to estrone and estradiol in peripheral tissues (adipose, muscle, and liver), catalyzed by the aromatase enzyme, is the principal source of estrogens. Anastrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P-450 unit of the enzyme; suppression of estrogen biosynthesis in all tissues reduces serum concentrations of circulating estrogens, including estrone, estradiol, and estrone sulfate. Anastrozole selectively inhibits synthesis of estrogens and does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone. In animals, anastrozole has not been shown to possess direct progestogenic, androgenic, or estrogenic activity, but alterations in the circulating concentrations of progesterone, androgens, and estrogens have been observed.

Pharmacodynamics

Anastrozole prevents the conversion of adrenal androgens (e.g. [testosterone]) to estrogen in peripheral and tumour tissues. As the growth of many breast cancers is stimulated and/or maintained by the presence of estrogen, anastrozole helps to treat these cancers by decreasing the levels of circulating estrogens. Anastrozole has a relatively long duration of action allowing for once daily dosing - serum estradiol is reduced by approximately 70% within 24 hours of beginning therapy with 1mg once daily, and levels remain suppressed for up to 6 days following cessation of therapy. The incidence of ischemic cardiovascular events was increased during anastrozole therapy and patients with pre-existing ischemic heart disease should consider the risks and benefits of anastrozole before beginning therapy. Anastrozole has also been reported to decrease spine and hip bone mineral density (BMD), so consideration should be given to monitoring of BMD in patients receiving long-term therapy.