Anastrozole (Monograph)

Brand name: Arimidex
Drug class: Antiestrogens
- Aromatase Inhibitors
Chemical name: α,α,α′,α′-Tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-benzenediacetonitrile
Molecular formula: C₁₇H₁₉N₅
CAS number: 120511-73-1

Medically reviewed by Drugs.com on May 12, 2025. Written by ASHP.

Introduction

Antineoplastic agent; selective aromatase inhibitor (type II).

Uses for Anastrozole

Initial, Sequential, or Extended Adjuvant Therapy for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer

Initial (primary) adjuvant therapy in postmenopausal women with early-stage hormone receptor-positive breast cancer.

Sequential adjuvant therapy^{† [off-label]} following 2–3 years of adjuvant tamoxifen for early-stage hormone receptor-positive breast cancer in postmenopausal women.

Extended adjuvant therapy^{† [off-label]} following 5 years of adjuvant tamoxifen for early-stage hormone receptor-positive breast cancer in postmenopausal women.

Guidelines from ASCO states that postmenopausal women with node-positive hormone receptor-positive breast cancer should be offered extended adjuvant endocrine therapy with one of the following: aromatase inhibitor therapy for up to a total of 10 years; tamoxifen for 10 years; tamoxifen for 5 years, then an aromatase inhibitor for 5 years; or tamoxifen for 2–3 years, then an aromatase inhibitor for 7–8 years. Women with node-negative breast cancer may also be offered extended adjuvant endocrine therapy for up to a total of 10 years, but benefits are likely narrower due to lower risk for recurrence.

Consider adverse effects, patient preference, and preexisting conditions when selecting an adjuvant regimen; during the course of adjuvant therapy, patients who are intolerant of one treatment may be switched to a different treatment.

Adjuvant Therapy for Early-stage Breast Cancer in Premenopausal Women

Use of endocrine therapy (i.e., anastrozole, exemestane, letrozole, tamoxifen) in combination with ovarian suppression^{† [off-label]} as adjuvant therapy in premenopausal women^{† [off-label]} with early-stage hormone receptor-positive breast cancer may be considered a reasonable choice (accepted).

Advanced Breast Cancer in Postmenopausal Women

First-line therapy for hormone receptor-positive (i.e., estrogen receptor-positive, progesterone receptor-positive, or both) or hormone receptor-unknown locally advanced or metastatic breast cancer in postmenopausal women.

Second-line therapy for advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Usually ineffective in patients with estrogen receptor-negative breast cancer and those who fail tamoxifen therapy.

According to ASCO, combination therapy with a nonsteroidal aromatase inhibitor (e.g., letrozole, anastrozole) and a cyclin-dependent kinase (CDK) 4/6 inhibitor should be offered first line to postmenopausal patients with treatment-naive hormone receptor-positive metastatic breast cancer; for some patients, monotherapy with an aromatase inhibitor may be appropriate. Choice of second-line hormonal therapy should take into account prior treatment exposure and response to previous endocrine therapy; options for second-line therapy include tamoxifen, an aromatase inhibitor, or fulvestrant with or without everolimus.

Advanced Breast Cancer in Premenopausal Women

For first-line treatment of premenopausal women with treatment-naive, hormone receptor-positive metastatic breast cancer^{† [off-label]}, ASCO recommends combination therapy with a nonsteroidal aromatase inhibitor (e.g., letrozole, anastrozole) and a CDK 4/6 inhibitor, in conjunction with chemical ovarian function suppression. Ovarian suppression or ablation in combination with hormonal therapy should be offered to premenopausal women with metastatic hormone receptor-positive breast cancer; patients without prior exposure to hormonal therapy may be treated with tamoxifen or ovarian suppression/ablation alone, but combination therapy is preferred.

Reduction in the Incidence of Breast Cancer in Women at High Risk

Has been used for reduction in the incidence of breast cancer^† in women at high risk for developing the disease.

Anastrozole Dosage and Administration

General

Pretreatment Screening

Perform pregnancy testing in females of reproductive potential prior to starting anastrozole.

Patient Monitoring

Consider bone density monitoring during therapy.
Consider cholesterol monitoring during therapy.

Other General Considerations

Concomitant corticosteroid replacement therapy not required.

Administration

Oral Administration

Administer orally once daily without regard to meals.

Dosage

Adults

Breast Cancer

Initial, Sequential, or Extended Adjuvant Therapy for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer

Oral

1 mg once daily.

Optimum duration unknown; duration of therapy in clinical study was 5 years.

Sequential and/or extended adjuvant therapy^†: ASCO states that postmenopausal women with node-positive hormone receptor-positive early breast cancer should be offered extended adjuvant endocrine therapy with one of the following: aromatase inhibitor therapy for up to a total of 10 years; tamoxifen for 10 years; tamoxifen for 5 years, then an aromatase inhibitor for 5 years; or tamoxifen for 2–3 years, then an aromatase inhibitor for 7–8 years. Women with node-negative breast cancer may also be offered extended adjuvant endocrine therapy for up to a total of 10 years, although benefits are likely narrower due to lower risk for recurrence.

Adjuvant Therapy for Early-Stage Breast Cancer in Premenopausal Women†

Oral

Dosage of 1 mg once daily has been used in combination with ovarian suppression^†.

Advanced Breast Cancer in Postmenopausal Women

Oral

1 mg once daily. Continue therapy until tumor progresses.

Reduction in the Incidence of Breast Cancer in Women at High Risk†

Oral

Dosage of 1 mg once daily for 5 years has been used.

Special Populations

Hepatic Impairment

Dosage adjustment not required in patients with mild to moderate hepatic impairment or stable hepatic cirrhosis.

Not studied in patients with severe hepatic impairment.

Renal Impairment

Dosage adjustment not required.

Geriatric Patients

Dosage adjustment not required.

Cautions for Anastrozole

Contraindications

Known hypersensitivity to anastrozole or any ingredient in the formulation.

Warnings/Precautions

Ischemic Cardiovascular Effects

Increased incidence of ischemic cardiovascular events (e.g., angina pectoris) reported in patients with preexisting ischemic heart disease; consider risks and benefits of therapy in these patients.

Bone Effects

Bone mineral density (BMD) at lumbar spine and hip decreased in patients receiving anastrozole and increased in those receiving tamoxifen as initial (primary) adjuvant therapy. Incidence of fractures was higher with anastrozole versus tamoxifen during treatment, but not following completion of treatment.

Consider BMD monitoring in patients receiving anastrozole.

Cholesterol

Increases in total serum cholesterol reported during therapy.

Consider cholesterol monitoring in patients receiving anastrozole.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxic and fetotoxic in animals. Test for pregnancy prior to initiation of the drug. Advise females of reproductive potential to use effective contraceptive methods during therapy and for ≥3 weeks after discontinuance of the drug. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Specific Populations

Pregnancy

May cause fetal harm; embryotoxic and fetotoxic in animals. Test for pregnancy prior to initiation of the drug. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Lactation

Not known whether anastrozole or its metabolites are distributed into human milk; effects on nursing infant and milk production also unknown. Discontinue nursing during therapy and for 2 weeks after drug discontinuance.

Females of Reproductive Potential

May cause fetal harm; embryotoxic, fetotoxic, and abortifacient in animals. Perform pregnancy test prior to initiation of anastrozole therapy in females of reproductive potential and advise such patients to use effective contraceptive methods during therapy and for ≥3 weeks after discontinuance of the drug.

Impairment of fertility and effects on the reproductive organs demonstrated in animal studies.

Pediatric Use

Has been used in clinical studies of adolescent boys 11–18 years of age with pubertal gynecomastia^† and in girls 2 to <10 years of age with McCune-Albright syndrome and progressive precocious puberty^†; however, efficacy not established for these indications.

Geriatric Use

For adjuvant treatment of hormone receptor-positive early-stage breast cancer, efficacy (e.g., disease-free survival benefit) in women ≥65 years of age was less than efficacy observed in postmenopausal women <65 years of age.

No substantial differences in efficacy for patients ≥65 years of age relative to younger adults when used as second line therapy for advanced breast cancer; moderately greater efficacy observed for patients ≥65 years of age when used as first-line therapy for locally advanced or metastatic breast cancer.

Hepatic Impairment

Not studied in patients with severe hepatic impairment. No dosage adjustment required in patients with mild to moderate hepatic impairment or stable hepatic cirrhosis.

Renal Impairment

Total body clearance of anastrozole reduced by only 10% in patients with severe renal impairment; adjustment of anastrozole dosage not required in patients with renal impairment.

Common Adverse Effects

Early breast cancer (≥10%): hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea, vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema, and lymphedema.

Advanced breast cancer (≥10%): hot flashes, nausea, asthenia, pain, headache, back pain, bone pain, increased cough, dyspnea, pharyngitis, and peripheral edema.

Drug Interactions

Inhibits CYP1A2, 2C8/9, and 3A4 in vitro, but only at relatively high concentrations. Does not inhibit CYP2A6 or CYP2D6 in vitro. Pharmacokinetic interaction unlikely with drugs metabolized by CYP isoenzymes at recommended dosages.

Specific Drugs

Drug	Interaction	Comment
Antipyrine	Pharmacokinetic interaction unlikely
Estrogens	Antagonistic pharmacologic effects	Concomitant use not recommended

Tamoxifen	Possible decreased plasma anastrozole concentrations; concomitant use does not improve efficacy	Concomitant use not recommended
Warfarin	No clinically important effects on anticoagulant activity or pharmacokinetics of warfarin

Anastrozole Pharmacokinetics

Absorption

Bioavailability

Rapidly and well absorbed after oral administration, with peak plasma concentrations usually attained within 2 hours under fasting conditions.

Steady-state plasma concentrations achieved in about 7 days.

Onset

Serum estradiol concentrations reduced by approximately 70% within 24 hours of a 1-mg dose and by approximately 80% after 14 days of daily dosing.

Duration

Suppression of serum estradiol concentrations maintained for up to 6 days after discontinuance of daily anastrozole administration.

Food

Food reduces rate but does not affect extent of absorption.

Distribution

Extent

Anastrozole crosses the placenta in animals; not known whether anastrozole crosses the placenta in humans.

Not known whether anastrozole is distributed into milk.

Plasma Protein Binding

40%.

Elimination

Metabolism

Undergoes N-dealkylation, hydroxylation, and glucuronidation in the liver to multiple, pharmacologically inactive, metabolites.

Elimination Route

Hepatic metabolism (85%) and renal excretion (10%).

Half-life

Approximately 50 hours.

Special Populations

No evidence of altered pharmacokinetics observed in women >80 years of age compared with women <50 years of age.

Individuals with severe renal impairment (Cl_cr <30 mL/minute): Renal clearance decreased by approximately 50%, but total body clearance decreased by only 10%.

Individuals with stable hepatic cirrhosis (related to alcohol abuse): Clearance reduced by approximately 30% compared with those with normal hepatic function; however, plasma concentrations within range compared with individuals with normal hepatic function.

Stability

Storage

Oral

Tablets

20–25°C.

Actions

Selectively inhibits conversion of androgens to estrogens.
Decreased serum and tumor concentrations of estrogen inhibit breast tumor growth and delay disease progression.
Does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone.

Advice to Patients

Provide patient with a copy of the manufacturer’s patient information.
Risk of osteoporosis. Importance of BMD monitoring.
Risk of fetal harm if used during pregnancy. Necessity of advising females of reproductive potential to use effective contraception during anastrozole therapy and for ≥3 weeks after the last dose. Importance of women informing clinicians immediately if they become pregnant or pregnancy is suspected during therapy. If pregnancy occurs, advise pregnant women of potential risk to the fetus.
Importance of advising women to avoid breast-feeding while receiving anastrozole and for 2 weeks following discontinuance of therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., estrogens, tamoxifen), and OTC drugs, as well as any concomitant illnesses.
Increased risk of ischemic cardiovascular events in patients with preexisting ischemic heart disease.
Importance of immediately informing clinician if manifestations of a serious allergic reaction (e.g., swelling of face, lips, tongue, and/or throat; difficulty in swallowing and/or breathing) occur.
Risk of hypercholesterolemia.
Importance of informing clinician if tickling, tingling, or numbness occurs.
Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name