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, 2004-2014, Selected Revisions November 5, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. AstraZeneca. Arimidex (anastrozole) tablets prescribing information. Wilmington, DE; 2011 Apr.
2. Jonat W, Howell A, Blomqvist C et al for the Arimidex Study Group. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996; 32A:404-12. [PubMed 8814682]
3. Plourde PV, Dyroff M, Dukes M. Arimidex: a potent and selective fourth- generation aromatase inhibitor. Breast Cancer Res Treat. 1994; 30:103-11. [PubMed 7949201]
4. Plourde PV, Dyroff M, Dowsett M et al. Arimidex: a new oral, once-a-day aromatase inhibitor. J Steroid Biochem Mol Biol. 1995; 53:175-9. [PubMed 7626450]
5. Brodie AMH. Aromatase inhibitors in the treatment of breast cancer. J Steroid Biochem Mol Biol. 1994; 49:281-7. [PubMed 8043490]
6. Yates RA, Dowsett M, Fisher GV et al. Arimidex (ZD1033): a selective, potent inhibitor of aromatase in post-menopausal female volunteers. Br J Cancer. 1996; 73:543- 8. [PubMed 8595172]
7. Goss PE, Gwyn KMEH. Current perspectives on aromatase inhibitors in breast cancer. J Clin Oncol. 1994; 12:2460-70. [IDIS 338078] [PubMed 7964964]
8. Buzdar AU, Plourde PV, Jones SE et al and the N American Arimidex Study Group. Randomized phase III study of the new selective aromatase inhibitor arimidex (A) (ZD1033) versus megestrol acetate (MA) in the treatment of postmenopausal women with advanced breast cancer. Breast. 1995; 4:256-7.
9. Zeneca Pharmaceuticals. Arimidex (anastrozole) product monograph. Wilmington, DE; 1996 Mar.
10. Zeneca Pharmaceuticals. Arimidex (anastrozole) tablets product review. Wilmington, DE; 1996 Mar.
11. Baldinger SL, DeFusco P. Focus on anastrozole: an aromatase inhibitor for the treatment of hormonally dependent advanced breast cancer. Formulary. 1996; 31:363- 73.
12. Zeneca Pharmaceuticals, Wilmington, DE: Personal communication.
13. Harris JR, Morrow M, Bonadonna G. Cancer of the breast. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia, PA: J.B. Lippincott; 1993:1264-332.
14. Higa GM, AlKhouri N. Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer. Am J Health-Syst Pharm. 1998; 55:445-52. [IDIS 401376] [PubMed 9522927]
15. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]
16. Ibrahim NK, Buzdar AU. Aromatase inhibitors: current status. Am J Clin Oncol. 1995; 18:407-17. [IDIS 354571] [PubMed 7572758]
17. Lonning PE. Aromatase inhibition for breast cancer treatment. Acta Oncol. 1996; 35(Suppl 5):38-43. [PubMed 9142963]
18. Food and Drug Administration. Labeling and prescription drug advertising; content and format for labeling for human prescription drugs. 21 CFR Parts 201 and 202. Final Rule. [Docket No. 75N-0066] Fed Regist. 1979; 44:37434-67.
19. Department of Health and Human Services, Food and Drug Administration. Subpart B—Labeling requirements for prescription drugs and/or insulin. (21 CFR Ch. 1 (4-1-87 Ed.). 1987:18-24.
20. Breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2011 Nov 21.
21. Bonneterre J, Thurlimann B, Robertson JFR et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000; 18:3748-57. [IDIS 465845] [PubMed 11078487]
22. Nabholtz JM, Buzdar A, Pollak M et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol. 2000; 18:3758-67. [IDIS 465846] [PubMed 11078488]
23. Buzdar AU, Jonat W, Howell A et al. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998; 83:1142-52. [IDIS 414664] [PubMed 9740079]
24. Baum M, Budzar AU, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002; 359:2131-9. [PubMed 12090977]
25. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: status report 2002. J Clin Oncol. 2002; 20:3317-27. [IDIS 486566] [PubMed 12149306]
26. The ATAC Trialists’ Group. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the ‘ArimidexTM and Tamoxifen Alone or in Combination’ (ATAC) trial. Br J Cancer. 2001; 85:317-24. [PubMed 11487258]
27. Baum M, Buzdar A, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003; 98:1802-10. [IDIS 506528] [PubMed 14584060]
28. Ravdin P. Aromatase inhibitors for the endocrine adjuvant treatment of breast cancer. Lancet. 2002; 359:2126-7. [IDIS 483590] [PubMed 12090973]
29. Stasi R, Terzoli E. Questions about anastrozole for early breast cancer. Lancet. 2002; 360:1890. [IDIS 490874] [PubMed 12480404]
30. Baum M. Questions about anastrozole for early breast cancer. Lancet. 2002; 360:1890-1.
31. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment working group update: use of aromatase inhibitors in the adjuvant setting. J Clin Oncol. 2003; 21:2597-9. [IDIS 499512] [PubMed 12732612]
32. Cuzick J, Buzdar A, Baum M et al. Adjuvant use of anastrozole in breast cancer. J Clin Oncol. 2004; 22:1524-6. [IDIS 516237] [PubMed 15084628]
33. The ASCO Aromatase Inhibitors Technology Assessment Working Group. Adjuvant use of anastrozole in breast cancer: author reply. J Clin Oncol. 2004; 22:1526-7.
34. Fleming GF. Adjuvant aromatase inhibitors: are we there yet? Cancer. 2003; 98:1779-81.
35. Carraway H, Wolff AC. Anastrozole is safer and may be more effective than tamoxifen in postmenopausal women with early-stage breast cancer. Cancer Treat Rev. 2004; 30:303-7. [PubMed 15059653]
36. Hilner BE, Ingle JN, Chelbowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21:4042-57. [IDIS 513063] [PubMed 12963702]
37. Wellington K, Faulds DM. Anastrozole: in early breast cancer. Drugs. 2002; 62:2483-90; discussion 2491-2. [PubMed 12421108]
38. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 20-541/S-006: Medical Reviews. From FDA web site.
39. Costa SD, Kaufmann M. Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer? J Clin Oncol. 2001; 19:2580. Letter.
40. Bagley CM Jr, Rowbotham RK. Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer? J Clin Oncol. 2001; 19:2578-9. Letter.
41. Gluck S. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor-positive advanced breast carcinoma. Cancer. 2002; 95:2442-3. [PubMed 12436453]
42. Donnellan PP, Douglas SL, Cameron DA et al. Aromatase inhibitors and arthralgia. J Clin Oncol. 2001; 19:2767. [IDIS 464684] [PubMed 11352973]
43. Eastell R, Adams JE, Coleman RE et al. Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008; 26:1051-8. [PubMed 18309940]
44. Chlebowski RT, Col N, Winer EP et al. American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol. 2002; 20:3328-43. [IDIS 486567] [PubMed 12149307]
45. Forward DP, Cheung KL, Jackson L et al. Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer. Br J Cancer. 2004; 90:590-4. [PubMed 14760369]
46. Reviewers’ comments (personal observations).
47. AstraZeneca. Wilmington, DE: Personal communication.
48. Food and Drug Administration. MedWatch—Safety-related drug labeling changes: Arimidex (anastrozole tablets) [Aug 2004]. From FDA web site.
49. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol. 2005; 23:619-29. [PubMed 15545664]
50. Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005; 365:60-2. [PubMed 15639680]
51. Boccardo F, Rubagotti A, Puntoni M et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol. 2005; 23:5138-47. [PubMed 16009955]
52. Jakesz R, Jonat W, Gnant M et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005; 366:455-62. [PubMed 16084253]
53. Jonat W, Gnant M, Boccardo F et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Lancet Oncol. 2006; 7:991-6. [PubMed 17138220]
54. Jakesz R, Greil R, Gnant M et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007; 99:1845-53. [PubMed 18073378]
55. Nabholtz JM, Bonneterre J, Buzdar A et al. Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer. 2003; 39:1684-9. [PubMed 12888362]
56. Mauri D, Pavlidis N, Polyzos NP et al. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst. 2006; 98:1285-91. [PubMed 16985247]
57. Fallowfield L, Cella D, Cuzick J et al. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. J Clin Oncol. 2004; 22:4261-71. [PubMed 15514369]
58. Eisner A, Falardeau J, Toomey MD et al. Retinal hemorrhages in anastrozole users. Optom Vis Sci. 2008; 85:301-8. [PubMed 18451730]
59. Partridge AH, LaFountain A, Mayer E et al. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008; 26:556-62. [PubMed 18180462]
60. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008; 9:45-53.
61. Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010; 28:3784-96. [PubMed 20625130]
62. AstraZeneca. Arimidex (anastrozole) tablets prescribing information. Wilmington, DE; 2008 Aug.
63. Boccardo F, Rubagotti A, Guglielmini P et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial. Ann Oncol. 2006; 17 Suppl 7:vii10-4. [PubMed 16760270]
64. Dubsky PC, Jakesz R, Mlineritsch B et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012; 30:722-8. [PubMed 22271481]
65. Kaufmann M, Jonat W, Hilfrich J et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007; 25:2664-70. [PubMed 17563395]
66. Cuzick J, Sestak I, Baum M et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010; 11:1135-41. [PubMed 21087898]
67. Duffy S, Jackson TL, Lansdown M et al. The ATAC adjuvant breast-cancer trial: six-year results of the endometrial subprotocol. J Obstet Gynaecol. 2010; 30:596-604. [PubMed 20701510]
68. Cella D, Fallowfield L, Barker P et al. Quality of life of postmenopausal women in the ATAC (“Arimidex”, tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer. Breast Cancer Res Treat. 2006; 100:273-84. [PubMed 16944295]