Generic Name: Anastrozole
Class: Antineoplastic Agents
VA Class: AN900
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
Uses for Arimidex
Aromatase inhibitors are a treatment of choice for adjuvant hormonal therapy to lower risk of breast cancer recurrence in postmenopausal women with early-stage hormone receptor-positive breast cancer.20 61 An aromatase inhibitor-containing regimen is modestly more effective than tamoxifen alone.20 61
ASCO states that most postmenopausal women with early-stage hormone receptor-positive breast cancer should consider receiving an aromatase inhibitor during the course of adjuvant therapy, either as primary (initial) therapy or following 2–3 years of tamoxifen (sequential therapy), for a total of 5 years of adjuvant endocrine therapy.61 Data also support switching to an aromatase inhibitor following 5 years of adjuvant tamoxifen (extended adjuvant therapy).61 ASCO states that women who receive extended adjuvant therapy should receive tamoxifen for 5 years followed by an aromatase inhibitor for 3–5 years.61
Consider adverse effects, patient preference, and preexisting conditions when selecting an adjuvant regimen.61 Joint disorders (arthritis, arthrosis, arthralgia), fractures, and elevated cholesterol reported more frequently in patients receiving adjuvant anastrozole,1 whereas adverse gynecologic effects (endometrial cancer, vaginal discharge, vaginal bleeding), hot flushes, ischemic cerebrovascular events, and venous thromboembolism reported more frequently in those receiving adjuvant tamoxifen.1 50
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.1 15 20
Second-line therapy for advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.1 20 Usually ineffective in patients with estrogen receptor-negative breast cancer and those who fail tamoxifen therapy.1
Arimidex Dosage and Administration
Administer orally once daily without regard to meals.1
Adjuvant Treatment of Early-stage Breast CancerOral
1 mg once daily.1
Initial adjuvant therapy: Optimum duration unknown; duration of therapy in clinical study was 5 years.1 In patients who discontinue aromatase inhibitor therapy prior to 5 years, ASCO recommends consideration of tamoxifen to complete the 5-year adjuvant regimen.61
Sequential adjuvant therapy†: Optimal time to switch from tamoxifen to aromatase inhibitor therapy is unknown.61 ASCO states that disease-free patients may switch to an aromatase inhibitor after 2–3 years of adjuvant tamoxifen therapy to complete a 5-year sequential adjuvant regimen.61
Extended adjuvant therapy†: ASCO recommends that patients who receive an extended adjuvant regimen receive an aromatase inhibitor (e.g., anastrozole) for 3–5 years beyond the initial 5 years of tamoxifen therapy, to complete a total of 8–10 years of adjuvant endocrine therapy.61
First-line Treatment of Advanced Breast CancerOral
Second-line Treatment of Advanced Breast CancerOral
Adjuvant Treatment of Early-stage Breast CancerOral
Maximum 5 years of aromatase inhibitor therapy; toxicity beyond 5 years not established.61
Dosage adjustment not required in patients with mild to moderate hepatic impairment or stable hepatic cirrhosis.1 (See Special Populations under Pharmacokinetics.)
Not studied in patients with severe hepatic impairment.1
Dosage adjustment not required.1 (See Special Populations under Pharmacokinetics.)
Dosage adjustment not required.1 (See Special Populations under Pharmacokinetics.)
Cautions for Arimidex
Known hypersensitivity to anastrozole or any ingredient in the formulation.1
Premenopausal women.1 (See Premenopausal Women under Cautions.)
Pregnancy.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
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.1
Effects on Bone
Postmenopausal women receiving an aromatase inhibitor as adjuvant therapy are at high risk for osteoporosis.36
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.1 43 48 Incidence of fractures was higher with anastrozole versus tamoxifen during treatment, but not following completion of treatment.1 66
Lifestyle changes (e.g., weight-bearing exercise, abstinence from smoking, moderation in alcohol consumption) and supplemental calcium and vitamin D recommended in all women receiving adjuvant anastrozole therapy.36 46 47
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; embryotoxic and fetotoxic in animals.1 Contraindicated in women who are or may become pregnant (i.e., premenopausal women).1 If inadvertently used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1
Category X.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether anastrozole is distributed into milk; discontinue nursing or the drug.1
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.1
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.1
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;1 moderately greater efficacy observed for patients ≥65 years of age when used as first-line therapy for locally advanced or metastatic breast cancer.1
Not studied in patients with severe hepatic impairment.1
Common Adverse Effects
Initial adjuvant therapy: Vasodilation, hot flushes (flashes), fatigue/asthenia, mood disturbance, pain, arthritis, arthralgia.1
Advanced-stage disease: GI disturbance (e.g., nausea), hot flushes, vasodilation, nausea, asthenia.1
Interactions for Arimidex
Inhibits CYP1A2, 2C8/9, and 3A4 in vitro, but only at relatively high concentrations.1 Does not inhibit CYP2A6 or CYP2D6 in vitro.1 Pharmacokinetic interaction unlikely with drugs metabolized by CYP isoenzymes at recommended dosages.1
Pharmacokinetic interaction unlikely1
Antagonistic pharmacologic effects1
Concomitant use not recommended1
No clinically important effects on anticoagulant activity or pharmacokinetics of warfarin1
Rapidly and well absorbed after oral administration, with peak plasma concentrations usually attained within 2 hours under fasting conditions.1
Steady-state plasma concentrations achieved in about 7 days.1
Suppression of serum estradiol concentrations maintained for up to 6 days after discontinuance of daily anastrozole administration.1
Food reduces rate but does not affect extent of absorption.1
Not known whether anastrozole is distributed into milk.1
Plasma Protein Binding
Undergoes N-dealkylation, hydroxylation, and glucuronidation in the liver to multiple, pharmacologically inactive, metabolites.1
Hepatic metabolism (85%) and renal excretion (10%).1
Approximately 50 hours.1
No evidence of altered pharmacokinetics observed in women >80 years of age compared with women <50 years of age.1
Individuals with severe renal impairment (Clcr <30 mL/minute): Renal clearance decreased by approximately 50%, but total body clearance decreased by only 10%.1
Individuals with stable hepatic cirrhosis (related to alcohol abuse): Clearance reduced by approximately 30% compared with those with normal hepatic function;1 however, plasma concentrations within range compared with individuals with normal hepatic function.1
Advice to Patients
Importance of providing patient with a copy of the manufacturer’s patient information.1
Risk of osteoporosis.1 Life-style changes (e.g., weight-bearing exercise, abstinence from smoking, moderation of alcohol consumption) and dietary supplementation with calcium and vitamin D advised.36 46 47 Importance of considering BMD monitoring.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., estrogens, raloxifene, tamoxifen), and OTC drugs, as well as any concomitant illnesses.1
Increased risk of ischemic cardiovascular events in patients with preexisting ischemic heart disease.1
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.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Anastrozole Film-coated Tablets
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Anastrozole 1MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$186.01 or 60/$359.96
Arimidex 1MG Tablets (ASTRAZENECA): 30/$458.97 or 90/$1,313.01
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions November 5, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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