ARIMIDEX 1 MG TABLETS

Indications

• Hormone receptor-positive breast cancer in postmenopausal women
• Adjuvant treatment of early breast cancer
• Treatment of advanced breast cancer

Dosage

Adults: The recommended dose for adults is 1 mg orally once daily.

Mechanism of action

Anastrozole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues. It interferes with the biosynthesis of estrogen from adrenally-produced androgens, effectively suppressing circulating estrogen levels and inhibiting the growth of hormone receptor-positive tumors.

Pharmacodynamics

Anastrozole prevents the conversion of adrenal androgens to estrogen in both peripheral and tumor tissues. This reduction in estrogen levels is vital for treating breast cancers that are stimulated or maintained by estrogen. Anastrozole has a long duration of action, allowing for once daily dosing, and serum estradiol levels are significantly reduced within 24 hours of administration, remaining suppressed for up to 6 days after discontinuation of therapy. However, it may increase the incidence of ischemic cardiovascular events and decrease bone mineral density, necessitating monitoring in long-term users.

Pharmacokinetics

Anastrozole is well absorbed after oral administration, with peak plasma concentrations occurring approximately 2 hours post-dose. The drug has a half-life of about 40 to 50 hours, allowing for sustained action with once-daily dosing. It is primarily metabolized in the liver via cytochrome P450 enzymes and is excreted in urine as metabolites. Notably, anastrozole does not affect the formation of adrenal corticosteroids or aldosterone.

Contra-indications

• Hypersensitivity to anastrozole or any of its components
• Pre-existing severe liver impairment

Adverse effects

• Hot flashes
• Nausea
• Fatigue
• Headache
• Joint pain
• Bone density loss
• Cardiovascular events

Interactions

• Estrogens - may reduce the effectiveness of anastrozole
• Tamoxifen - may interfere with the pharmacological action of anastrozole

Precautions

• Monitor bone mineral density in patients on long-term therapy
• Consider risks in patients with pre-existing ischemic heart disease
• Use with caution in patients with renal impairment

Pregnancy

Anastrozole is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether anastrozole is excreted in human milk; breastfeeding is not recommended during treatment.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

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.