Anastrozole

Generic Name

Anastrozole

Brand Name

Arimidex

Drug Class

Nonsteroidal aromatase inhibitor

Antineoplastic agent

Hormonal therapy – estrogen synthesis blocker

Mechanism of Action

Anastrozole selectively and reversibly inhibits the enzyme aromatase, which catalyzes the conversion of androgens (primarily androstenedione and testosterone) into estrogens (estrone and estradiol)

By reducing estrogen production, especially in postmenopausal women where peripheral tissues are the primary source of estrogen, it significantly decreases circulating estrogen levels

Since certain breast cancer cells rely on estrogen for proliferation, this estrogen deprivation results in tumor regression or growth inhibition in hormone receptor-positive cancers

Anastrozole does not possess progestogenic, androgenic, or estrogenic activity

Indications

Approved Uses

Hormone receptor-positive early breast cancer in postmenopausal women

First-line treatment of advanced or metastatic hormone receptor-positive breast cancer

Treatment of advanced breast cancer after disease progression following tamoxifen therapy

Adjuvant treatment in early-stage hormone-positive breast cancer as an alternative to tamoxifen or following its completion

Off-label Uses

Gynecomastia in males (including pubertal gynecomastia)

Ovulation induction in women with infertility due to PCOS

Endometriosis management

Prevention of estrogenic side effects in men on testosterone therapy

Male-to-female transgender hormone modulation (in certain protocols)

Aromatase inhibitor-induced delay of growth plate closure in adolescents with tall stature prediction

Dose and Administration

Breast Cancer (Adjuvant and Advanced)

1 mg orally once daily

Taken with or without food

Duration typically 5 years in adjuvant setting, but may be extended to 10 years based on recurrence risk

Infertility (off-label use)

1 mg daily for 5 days starting on day 3 of the menstrual cycle

Gynecomastia (off-label use in males)

0.5–1 mg daily for up to 6 months, depending on response

Growth modulation in adolescents (off-label)

Doses vary based on protocol, often 1 mg daily

Hepatic Impairment

No dose adjustment necessary in mild to moderate hepatic impairment

Caution advised in severe hepatic impairment

Renal Impairment

No dose adjustment necessary

Pharmacokinetics

Absorption: Rapid, with peak plasma levels within 2 hours

Bioavailability: ~83%

Half-life: Approximately 50 hours

Metabolism: Hepatic via N-dealkylation, hydroxylation, glucuronidation

Excretion: Primarily via urine (10% as unchanged drug) and feces

Steady-state levels achieved within 7 days of daily administration

Contraindications

Premenopausal women (except specific off-label indications)

Pregnancy and lactation

Known hypersensitivity to anastrozole or excipients

Concomitant use with tamoxifen reduces efficacy and is not recommended

Estrogen-containing therapies antagonize anastrozole and are contraindicated

Warnings and Precautions

Osteoporosis risk increases due to estrogen depletion

Fracture risk is significantly higher compared to tamoxifen

Baseline and periodic bone mineral density (DEXA scans) monitoring is recommended

Hypercholesterolemia may be exacerbated

Elevated hepatic transaminases reported, monitor liver function tests in long-term use

May cause ischemic cardiovascular events, especially in patients with pre-existing coronary artery disease

Should not be combined with estrogenic agents

Adverse Effects

Common

Hot flashes

Musculoskeletal pain (arthralgia, myalgia)

Fatigue

Nausea

Headache

Vaginal dryness

Decreased bone mineral density

Back pain

Less Common

Insomnia

Rash

Peripheral edema

Anorexia

Dizziness

Depression

Hypertension

Hypercholesterolemia

Sweating

Serious

Osteoporotic fractures (spine, hip, wrist)

Hepatotoxicity

Ischemic heart disease (angina, MI)

Thromboembolic events (rare but more common in combination therapies)

Allergic reactions (urticaria, anaphylaxis)

Pregnancy and Lactation

Pregnancy

Category X

Teratogenic and embryotoxic in animal studies

Contraindicated in pregnant women

Lactation

Unknown whether excreted in human milk

Contraindicated during breastfeeding

Drug Interactions

Tamoxifen

Significant reduction in plasma levels of anastrozole and antagonism of therapeutic effect

Avoid combination

Estrogens (HRT, contraceptives)

Counteract the mechanism of action of anastrozole

Avoid concurrent use

CYP Enzyme Inducers/Inhibitors

Minimal impact since anastrozole metabolism is not heavily reliant on CYP450

No significant known CYP-mediated drug interactions

Statins

Monitor lipid levels since hypercholesterolemia may be aggravated

No direct interaction but anastrozole may reduce HDL and increase LDL

Bisphosphonates (e.g. alendronate, zoledronic acid)

Often co-prescribed to mitigate bone loss

No direct interaction, used synergistically in high-risk patients

Monitoring Parameters

Bone mineral density every 1–2 years

Lipid profile periodically

Liver function tests in long-term therapy

Cardiac function in patients with a history of ischemic heart disease

Menstrual status to confirm postmenopausal state before initiating therapy

Signs of joint pain, fracture, or fatigue

Patient Counseling Points

Take once daily at the same time, with or without food

Report persistent or worsening bone pain or signs of fractures

Discuss bone protection strategies including calcium, vitamin D, and weight-bearing exercise

Avoid estrogen replacement therapy while using anastrozole

Hot flashes and musculoskeletal symptoms are common and may lessen over time

Inform physician if planning surgery or experiencing unusual fatigue, jaundice, or chest pain

Use effective contraception if of childbearing potential

Comparative Notes

Compared to tamoxifen

Anastrozole has superior disease-free survival in early-stage hormone-positive breast cancer in postmenopausal women

Lower incidence of endometrial cancer, thromboembolic events, and vaginal bleeding

Higher risk of osteoporosis and arthralgia

Compared to letrozole

Both are aromatase inhibitors with similar efficacy

Letrozole may provide slightly better overall survival in metastatic disease, but with slightly higher bone loss risk

Side effect profiles are broadly similar

Compared to exemestane

Anastrozole is non-steroidal and reversible

Exemestane is steroidal and irreversible

Both are used sequentially or interchangeably depending on response and tolerance

Use in Men

Though not formally approved, anastrozole is increasingly used in males for conditions associated with estrogen excess

In pubertal gynecomastia, it may reduce glandular volume and tenderness if initiated early

In testosterone replacement therapy, it prevents aromatization of testosterone to estradiol, minimizing estrogenic side effects like water retention or breast tenderness

Use in Fertility Treatments

In women with PCOS, anastrozole is used off-label as an ovulation induction agent due to its ability to reduce estrogen negative feedback on the hypothalamic-pituitary-ovarian axis, thereby increasing FSH and promoting follicular development

It may have a more favorable side effect profile than clomiphene and lower risk of multiple gestation

Storage and Stability

Store at room temperature below 25°C

Protect from moisture and light

Keep in original packaging until use

Formulation

Available as 1 mg oral tablets

Typically packaged in blisters of 28 or 30 tablets

Not available in injectable or extended-release forms