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Pronunciation
(an AS troe zole)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
First-line treatment of locally-advanced or metastatic breast cancer (hormone receptor-positive or unknown) in postmenopausal women; treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy; adjuvant treatment of early hormone receptor-positive breast cancer in postmenopausal women
Use: Unlabeled
Treatment of recurrent or metastatic endometrial or uterine cancers, treatment of recurrent ovarian cancer
Pregnancy Risk Factor
X
Pregnancy Considerations
Fetotoxicity was observed in animal studies. Anastrozole is contraindicated in women who are or may become pregnant (may cause fetal harm if administered during pregnancy). Use in premenopausal women with breast cancer does not provide any clinical benefit.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to anastrozole or any component of the formulation; use in women who are or may become pregnant
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Decreased bone mineral density: Due to decreased circulating estrogen levels, anastrozole is associated with a reduction in bone mineral density (BMD); decreases (from baseline) in total hip and lumbar spine BMD have been reported. Patients with pre-existing osteopenia are at higher risk for developing osteoporosis (Eastell, 2008). When initiating anastrozole treatment, follow available guidelines for bone mineral density management in postmenopausal women with similar fracture risk; concurrent use of bisphosphonates may be useful in patients at risk for fractures.
• Hypercholesterolemia: Elevated total cholesterol levels (contributed to by LDL cholesterol increases) have been reported in patients receiving anastrozole; use with caution in patients with hyperlipidemias. Cholesterol levels should be monitored/managed in accordance with current guidelines for patients with LDL elevations.
Disease-related concerns:
• Hepatic impairment: Plasma concentrations in patients with stable hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. Has not been studied in patients with severe hepatic impairment.
• Ischemic disease: Patients with pre-existing ischemic cardiac disease have an increased risk for ischemic cardiovascular events.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
• Pregnancy: Use is contraindicated in women who are or may become pregnant.
• Premenopausal women: Anastrozole offers no clinical benefit in premenopausal women with breast cancer.
Adverse Reactions
>10%:
Cardiovascular: Vasodilatation (25% to 36%), ischemic cardiovascular disease (4%; 17% in patients with pre-existing ischemic heart disease), hypertension (2% to 13%), angina (2%; 12% in patients with pre-existing ischemic heart disease)
Central nervous system: Mood disturbance (19%), fatigue (19%), pain (11% to 17%), headache (9% to 13%), depression (5% to 13%)
Dermatologic: Rash (6% to 11%)
Endocrine & metabolic: Hot flashes (12% to 36%)
Gastrointestinal: Nausea (11% to 19%), vomiting (8% to 13%)
Neuromuscular & skeletal: Weakness (16% to 19%), arthritis (17%), arthralgia (2% to 15%), back pain (10% to 12%), bone pain (6% to 11%), osteoporosis (11%)
Respiratory: Pharyngitis (6% to 14%), cough increased (8% to 11%)
1% to 10%:
Cardiovascular: Peripheral edema (5% to 10%), chest pain (5% to 7%), edema (7%), venous thromboembolic events (2% to 4%), ischemic cerebrovascular events (2%), MI (1%)
Central nervous system: Insomnia (2% to 10%), dizziness (6% to 8%), anxiety (2% to 6%), fever (2% to 5%), malaise (2% to 5%), confusion (2% to 5%), nervousness (2% to 5%), somnolence (2% to 5%), lethargy (1%)
Dermatologic: Alopecia (2% to 5%), pruritus (2% to 5%)
Endocrine & metabolic: Hypercholesterolemia (9%), breast pain (2% to 8%)
Gastrointestinal: Diarrhea (8% to 9%), constipation (7% to 9%), abdominal pain (7% to 9%), weight gain (2% to 9%), anorexia (5% to 7%), xerostomia (6%), dyspepsia (7%), weight loss (2% to 5%)
Genitourinary: Urinary tract infection (2% to 8%), vulvovaginitis (6%), pelvic pain (5%), vaginal bleeding (1% to 5%), vaginitis (4%), vaginal discharge (4%), vaginal hemorrhage (2% to 4%), leukorrhea (2% to 3%), vaginal dryness (2% to 5%)
Hematologic: Anemia (2% to 5%), leukopenia (2% to 5%)
Hepatic: Liver function tests increased (1% to 10%), alkaline phosphatase increased (1% to 10%), gamma GT increased (≤5%)
Local: Thrombophlebitis (2% to 5%)
Neuromuscular & skeletal: Fracture (1% to 10%), arthrosis (7%), paresthesia (5% to 7%), joint disorder (6%), myalgia (2% to 6%), neck pain (2% to 5%), carpal tunnel syndrome (3%), hypertonia (3%)
Ocular: Cataracts (6%)
Respiratory: Dyspnea (8% to 10%), sinusitis (2% to 6%), bronchitis (2% to 5%), rhinitis (2% to 5%)
Miscellaneous: Lymphedema (10%), infection (2% to 9%), flu-like syndrome (2% to 7%), diaphoresis (2% to 5%), cyst (5%), neoplasm (5%), tumor flare (3%)
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, bilirubin increased, CVA, cerebral ischemia, cerebral infarct, cutaneous vasculitis (including Henoch-Schönlein purpura), endometrial cancer, erythema multiforme, hepatitis, jaundice, joint pain, joint stiffness, liver inflammation, liver pain, liver swelling, myocardial ischemia, pulmonary embolus, retinal vein thrombosis; skin reactions (eg, blisters, lesions, ulcers); Stevens-Johnson syndrome, trigger finger, urticaria
Metabolism/Transport Effects
Inhibits CYP1A2 (weak), CYP2C8 (weak), CYP2C9 (weak), CYP3A4 (weak)
Drug Interactions
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
Estrogen Derivatives: May diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Tamoxifen: May decrease the serum concentration of Anastrozole. Risk D: Consider therapy modification
Storage
Store at 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Potent and selective nonsteroidal aromatase inhibitor. By inhibiting aromatase, the conversion of androstenedione to estrone, and testosterone to estradiol, is prevented, thereby decreasing tumor mass or delaying progression in patients with tumors responsive to hormones. Anastrozole causes an 85% decrease in estrone sulfate levels.
Pharmacodynamics/Kinetics
Onset of estradiol reduction: 70% reduction after 24 hours; 80% after 2 weeks therapy
Duration of estradiol reduction: 6 days
Absorption: Well absorbed; extent of absorption not affected by food
Protein binding, plasma: 40%
Metabolism: Extensively hepatic (~85%) via N-dealkylation, hydroxylation, and glucuronidation; primary metabolite (triazole) inactive
Half-life elimination: ~50 hours
Time to peak, plasma: ~2 hours without food; 5 hours with food
Excretion: Feces; urine (urinary excretion accounts for ~10% of total elimination, mostly as metabolites)
Dosage
Oral: Adults: Females: Postmenopausal:
Breast cancer, advanced: 1 mg once daily; continue until tumor progression
Breast cancer, early (adjuvant treatment): 1 mg once daily; optimal duration unknown, duration in clinical trial is 5 years
Dosage adjustment in renal impairment: Dosage adjustment not necessary
Dosage adjustment in hepatic impairment:
Mild-to-moderate impairment or stable hepatic cirrhosis: Dosage adjustment is not required
Severe hepatic impairment: Has not been studied in this population
Administration: Oral
May be administered with or without food.
Monitoring Parameters
Bone mineral density; total cholesterol and LDL
Dietary Considerations
May be taken with or without food.
Patient Education
Maintain adequate hydration, unless instructed to restrict fluid intake. Anastrozole may cause or worsen osteoporosis; discuss ways to decrease this risk with prescriber. You may experience dizziness or fatigue; nausea, vomiting, or loss of appetite; increased pelvic, bone, or tumor pain; hot flashes; rash; or loss of hair. Report chest pain, palpitations, persistent headache, or dizziness; unresolved nausea or vomiting; pain or burning on urination; unusual or persistent nervousness, confusion, or anxiety; flu-like symptoms; or respiratory difficulty.
Geriatric Considerations
No age-related changes in pharmacokinetics were noted in clinical trials.
Additional Information
Oncology Comment: The American Society of Clinical Oncology (ASCO) guidelines for adjuvant endocrine therapy in postmenopausal women with HR-positive breast cancer (Burstein, 2010) recommend considering aromatase inhibitor (AI) therapy at some point in the treatment course (primary, sequentially, or extended). Optimal duration at this time is not known; however, treatment with an AI should not exceed 5 years in primary and extended therapies, and 2-3 years if followed by tamoxifen in sequential therapy (total of 5 years). If initial therapy with AI has been discontinued before the 5 years, consideration should be taken to receive tamoxifen for a total of 5 years. The optimal time to switch to an AI is also not known, but data supports switching after 2-3 years of tamoxifen (sequential) or after 5 years of tamoxifen (extended). If patient becomes intolerant or has poor adherence, consideration should be made to switch to another AI or initiate tamoxifen.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness, confusion, insomnia, and anxiety are common
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess carefully for use cautions. Evaluate bone mineral density and cholesterol levels.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 1 mg
Arimidex®: 1 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Anastrozole)
1 mg (30): $186.01
Tablets (Arimidex)
1 mg (30): $458.97
References
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(23):3784-96.
Buzdar AU, Robertson JF, Eiermann W, et al, “An Overview of the Pharmacology and Pharmacokinetics of the Newer Generation Aromatase Inhibitors Anastrozole, Letrozole, and Exemestane,” Cancer, 2002, 95(9):2006-16.
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(12):1135-41.
del Carmen MG, Fuller AF, Matulonis U, et al, “Phase II Trial of Anastrozole in Women With Asymptomatic Müllerian Cancer,” Gynecol Oncol, 2003, 91(3):596-602.
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(7):1051-7.
Forbes JF, Cuzick J, Buzdar A, 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(1):45-53.
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(19):2664-70.
Kendall A, Dowsett M, Folkerd E, et al, “Caution: Vaginal Estradiol Appears to be Contraindicated in Postmenopausal Women on Adjuvant Aromatase Inhibitors,” Ann Oncol, 2006, 17(4):584-7.
Koberle D and Thurlimann B, “Anastrozole: Pharmacological and Clinical Profile in Postmenopausal Women With Breast Cancer,” Expert Rev Anticancer Ther, 2001, 1(2):169-76.
Lonning PE, Geisler J, and Dowsett M, “Pharmacological and Clinical Profile of Anastrozole,” Breast Cancer Res Treat, 1998, 49(Suppl 1):53-7.
Lonning P, Pfister C, Martoni A, et al, “Pharmacokinetics of Third-Generation Aromatase Inhibitors,” Semin Oncol, 2003, 30(4 Suppl 14):23-32.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Breast Cancer,” Version 3.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Ovarian Cancer,” Version 1.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Uterine Neoplasms,” Version 1.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/uterine.pdf
National Osteoporosis Foundation, “Clinician's Guide to Prevention and Treatment of Osteoporosis,” Washington, DC, 2010. Available at http://www.nof.org
Njar VC and Brodie AM, “Comprehensive Pharmacology and Clinical Efficacy of Aromatase Inhibitors,” Drugs, 1999, 58(2):233-55.
Rose PG, Brunetto VL, VanLe L, et al, “A Phase II Trial of Anastrozole in Advanced Recurrent or Persistent Endometrial Carcinoma: A Gynecologic Oncology Group Study,” Gynecol Oncol, 2000, 78(2):212-6.
“Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report,” Circulation, 2002, 106(25):3143-21.
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(3):619-29.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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