Breast cancer, advanced: Postmenopausal patients: Oral: 1 mg once daily; continue until tumor progression or unacceptable toxicity.
Breast cancer, advanced, estrogen receptor positive, HER2 negative (off-label combination):
Postmenopausal patients: Oral: 1 mg once daily (in combination with abemaciclib) until disease progression or unacceptable toxicity (Ref). Aromatase inhibitors have also been used in combination with palbociclib and ribociclib (Ref).
Premenopausal or perimenopausal patients: Oral: 1 mg once daily (in combination with ribociclib [and the luteinizing hormone-releasing hormone (LHRH) agonist goserelin]) until disease progression or unacceptable toxicity (Ref).
Breast cancer, early, adjuvant therapy:
Postmenopausal patients: Oral: 1 mg once daily.
Premenopausal patients with high-risk disease (off-label use): Oral: 1 mg once daily (in combination with ovarian function suppression) (Ref).
Duration of therapy: The American Society of Clinical Oncology (ASCO) guidelines for adjuvant endocrine therapy of hormone-receptor positive breast cancer (focused update) recommend a duration of 5 to 10 years of adjuvant endocrine therapy; some patients may be appropriate candidates for extended aromatase inhibitor (AI) therapy for up to a total of 10 years based on disease recurrence risk and nodal disease status. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Ref). In a phase 3 study with another AI (letrozole), treatment with an additional 5 years of AI therapy (for a total of 10 years of AI therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo), although overall survival was not significantly different between groups and bone-related adverse events occurred more frequently with letrozole versus placebo (Ref).
Breast cancer in male patients, hormone receptor positive (off-label use): Note: Should be used in combination with a gonadotropin-releasing hormone agonist/antagonist (Ref).
Adjuvant t herapy (alternative agent): May be used as adjuvant therapy in male patients with hormone receptor–positive breast cancer with a contraindication to tamoxifen. ASCO guidelines for management of male breast cancer recommend an initial duration of 5 years of adjuvant endocrine therapy; if there still is a high risk of recurrence, five additional years of endocrine therapy may be offered if the initial 5 years of adjuvant therapy have been completed and tolerated (Ref).
Advanced or metastatic disease: Oral: 1 mg once daily until disease progression or unacceptable toxicity (Ref). Endocrine therapy for males with advanced or metastatic, HR+, HER2-negative breast cancer may be sequenced as in females (Ref).
Breast cancer, risk reduction (off-label use): Postmenopausal patients ≥40 years of age: Oral: 1 mg once daily for 5 years (Ref).
Endometrial or uterine cancer, recurrent or metastatic (off-label use): Oral: 1 mg once daily (Ref).
Ovarian cancer, recurrent (off-label use): Oral: 1 mg once daily until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (~30%): Oral: No dosage adjustment necessary; when scheduled dose falls on dialysis days, administer after hemodialysis (Ref).
Peritoneal dialysis: Dialyzability unknown: Oral: No dosage adjustment necessary (Ref).
CRRT: Oral: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral: No dosage adjustment necessary; when scheduled dose falls on PIRRT days, administer after PIRRT (Ref).
Mild to moderate impairment or stable hepatic cirrhosis: No dosage adjustment necessary.
Severe hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling. However, some sources do not recommend anastrozole use in severe impairment (Ref).
Refer to adult dosing.
Anastrozole is associated with a decreased bone mineral density (BMD); decreases (from baseline) in total hip BMD (~7% loss after 5 years) and lumbar spine BMD (~6% loss after 5 years) have been reported (Ref). Anastrozole has been linked to bone resorption in postmenopausal females; therefore, an increased risk of osteoporosis and bone fracture should be considered when administering treatment (Ref).
Mechanism: Time-related; anastrozole decreases plasma estrogen levels up to 94% in postmenopausal women with estrogen-positive breast cancer. Low levels of estrogen have been linked to bone resorption leading to decreased BMD, especially at the lumbar spine (LS) and hip. This results in increased risk of osteoporosis and fracture (Ref).
Onset: Delayed; bone loss in LS occurred during the first 2 years of treatment with no additional loss seen in years 2 to 5. No slowing of bone loss occurred in the total hip BMD (Ref). There was a statistically significant LS BMD increase in the 2 years after discontinuing 5 years of treatment (Ref).
Risk factors:
• Longer durations of aromatase inhibitors (more than 3 years of therapy) (Ref).
• Preexisting known risk factors for BMD loss, osteoporosis, and fracture (includes preexisting osteopenia, age >65 years, years since menopause, body mass index <20 kg/m2, personal/family history, chronic glucocorticoid use >6 months, prior fragility fracture history, low bone mineral density, rheumatoid arthritis, and smoking) (Ref).
Ischemic heart disease has been reported, with an increased incidence of ischemic cardiovascular events in patients with preexisting ischemic heart disease (Ref). Angina pectoris and acute myocardial infarction (MI) have occurred.
Mechanism: Non-dose-related; idiosyncratic. Aromatase inhibitors (AIs), such as anastrozole, reduce the protective effects of estrogen, consequently leading to increases in vasoconstriction and atherosclerosis. Additionally, there is a dysregulation of lipid metabolism and potential risk of hyperlipidemia. Together, these factors may increase the risk of cardiovascular disease (CVD) in patients receiving AI for breast cancer treatment (Ref).
Timing: Varied; cardiac ischemia may occur at any time during treatment (Ref).
Risk factors:
• Preexisting CVD, including ischemic heart disease, or risk factors associated with CVD (Ref). In a large SEER-Medicare cohort evaluating MI risk with adjuvant hormone therapy, several preexisting conditions were associated with MI including diabetes with complications, heart failure, prior MI, coronary artery disease, and peripheral vascular disease. In patients with prior history of MI, hazard ratio was nearly 3-fold higher (Ref).
• Longer durations of AI therapy (more than 3 years of therapy) are associated with 18% to 26% increased risk of cardiovascular disease (Ref).
Musculoskeletal effects, including new onset or exacerbation of existing arthralgia, joint stiffness, and/or ostealgia, may occur with anastrozole (Ref); pain may be severe and/or continuous (Ref). Aromatase inhibitor-induced arthralgia (AIA) presents with symmetrical joint pains most commonly affecting hands, wrists, and knees (Ref). Trigger finger and carpal tunnel syndrome may also be common complaints (Ref). These adverse reactions may significantly affect quality of life and the risk of treatment nonadherence or discontinuation should be considered; treatment discontinuation due to musculoskeletal symptoms has been reported between 5% to 20% (Ref).
Mechanism: Non-dose-related; idiosyncratic. Exact mechanism is unknown; however, multiple mechanisms have been proposed involving estrogen depletion either as a direct or indirect cause. Proposed estrogen depletion mechanisms include direct local effects on joint tissues, increased inflammatory parameters such as IL-6 indirectly affecting central and peripheral nociception (Ref), decreased estradiol leading to a decrease in endogenous opioid levels (Ref), collagen degradation, and impaired regulation of cartilage structure (Ref).
Onset: Varied; the median time to onset of symptoms is 1.6 to 2 months with a range of 1 week to >10 months. Symptoms have been shown to peak ~6 months after initiation of treatment (Ref). By 18 months, 75% of patients in the ATAC trial had experienced significant improvement of their symptoms (Ref).
Risk factors:
• Prior menopausal hormone therapy or previous chemotherapy (Ref).
• Certain CYP19A1 single nucleotide polymorphisms (SNPs) have been associated with increased arthralgia symptoms and/or association with discontinuation of therapy due to intolerable arthralgia (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Angina pectoris (2%; 12% in patients with preexisting ischemic heart disease) (table 1) , hypertension (5% to 13%), ischemic heart disease (4%; increased incidence of ischemic cardiovascular events seen in patients with preexisting ischemic heart disease: 17%) (table 2) , vasodilation (25% to 36%)
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
Comments |
---|---|---|---|---|---|
2% |
2% |
Breast cancer |
3,092 |
3,094 |
N/A |
12% |
5% |
Breast cancer |
216 |
249 |
In patients with preexisting ischemic heart disease |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
Comments |
---|---|---|---|---|---|
4% |
3% |
Breast cancer |
3,092 |
3,094 |
N/A |
17% |
10% |
Breast cancer |
216 |
249 |
In patients with preexisting ischemic heart disease |
Dermatologic: Skin rash (6% to 11%)
Endocrine & metabolic: Hot flash (12% to 36%)
Gastrointestinal: Gastrointestinal distress (29% to 34%), nausea (11% to 19%), vomiting (≤13%)
Nervous system: Depression (5% to 13%), fatigue (≤19%), headache (9% to 13%), mood disorder (19%), pain (11% to 17%)
Neuromuscular & skeletal: Arthralgia (15%; literature suggests incidence as high as 36%) (Howell 2005) (table 3) , arthritis (17%) (table 4) , asthenia (≤19%), back pain (10% to 12%) (table 5) , ostealgia (7% to 11%) (table 6) , osteoporosis (11%; literature suggests incidence as high as 20% in patients with preexisting osteopenia after 3- to 6-years of anastrazole) (van Hellemond 2019) (table 7)
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
15% |
11% |
Breast cancer |
3,092 |
3,094 |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
17% |
14% |
Breast cancer |
3,092 |
3,094 |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
12% |
13% |
Breast cancer |
506 |
511 |
10% |
10% |
Breast cancer |
3,092 |
3,094 |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
11% |
10% |
Breast cancer |
506 |
511 |
7% |
6% |
Breast cancer |
3,092 |
3,094 |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
11% |
7% |
Breast cancer |
3,092 |
3,094 |
Respiratory: Increased cough (8% to 11%), pharyngitis (6% to 14%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (1% in patients with preexisting ischemic heart disease; 0.9%) (table 8) , cerebral ischemia (2%), chest pain (5% to 7%), deep vein thrombosis (2%), edema (7%), peripheral edema (5% to 10%), thromboembolic disease (3% to 4%), thrombophlebitis (2% to 5%), venous thrombosis (3%)
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
Comments |
---|---|---|---|---|---|
1% |
1% |
Breast cancer |
3,092 |
3,094 |
N/A |
0.9% |
3% |
Breast cancer |
216 |
249 |
In patients with preexisting ischemic heart disease |
Dermatologic: Alopecia (2% to 5%), diaphoresis (2% to 5%), pruritus (2% to 5%)
Endocrine & metabolic: Hypercholesterolemia (9%), increased gamma-glutamyl transferase (2% to 5%), weight gain (2% to 9%), weight loss (2% to 5%)
Gastrointestinal: Abdominal pain (7% to 9%), anorexia (5% to 7%), constipation (7% to 9%), diarrhea (8% to 9%), dyspepsia (7%), gastrointestinal disease (7%), xerostomia (4% to 6%)
Genitourinary: Leukorrhea (2% to 3%), mastalgia (8%), pelvic pain (5%), urinary tract infection (8%), vaginal discharge (4%), vaginal dryness (2%), vaginal hemorrhage (1% to 5%), vaginitis (4%), vulvovaginitis (6%)
Hematologic & oncologic: Anemia (4%), leukopenia (2% to 5%), lymphedema (10%), neoplasm (5%), tumor flare (3%)
Hepatic: Increased serum alanine aminotransferase (2% to 5%), increased serum alkaline phosphatase (2% to 5%), increased serum aminotransferase (2% to 5%)
Infection: Infection (9%)
Nervous system: Anxiety (6%), carpal tunnel syndrome (3%) (table 9) , confusion (2% to 5%), dizziness (6% to 8%), drowsiness (2% to 5%), hypertonia (3%), insomnia (6% to 10%), lethargy (1%), malaise (2% to 5%), nervousness (2% to 5%), paresthesia (5% to 7%)
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
3% |
0.7% |
Breast cancer |
3,092 |
3,094 |
Neuromuscular & skeletal: Arthropathy (6% to 7%) (table 10) , bone fracture (10%) (table 11) , myalgia (6%) (table 12) , neck pain (2% to 5%), pathological fracture (2% to 5%)
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
Comments |
---|---|---|---|---|---|
7% |
5% |
Breast cancer |
3,092 |
3,094 |
Described in Arimidex PI 2018.12 as “arthrosis” |
6% |
5% |
Breast cancer |
3,092 |
3,094 |
Described in Arimidex PI 2018.12 as “joint disorder” |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
10% |
7% |
Breast cancer |
3,092 |
3,094 |
Drug (Anastrozole) |
Comparator (Tamoxifen) |
Indication |
Number of Patients (Anastrozole) |
Number of Patients (Tamoxifen) |
---|---|---|---|---|
6% |
5% |
Breast cancer |
3,092 |
3,094 |
Ophthalmic: Cataract (6%)
Respiratory: Bronchitis (5%), dyspnea (8% to 10%), flu-like symptoms (6% to 7%), rhinitis (2% to 5%), sinusitis (6%)
Miscellaneous: Accidental injury (10%), cyst (5%), fever (2% to 5%)
<1%:
Dermatologic: Dermal ulcer, skin blister
Hematologic & oncologic: Endometrial carcinoma
Hepatic: Abnormal hepatic function tests, hepatitis, hepatomegaly, jaundice
Frequency not defined: Cardiovascular: Cerebral infarction (Sagara 2010), pulmonary embolism (Lycette 2006), retinal thrombosis (Eisner 2008)
Postmarketing:
Dermatologic: Dermatitis (Kim 2020), dermatologic disorder (lichen sclerosus) (Agrawal 2017; Potter 2013), erythema multiforme (Cozzani 2018; Wollina 2018), hypersensitivity angiitis (Shoda 2005), pruritic rash (Bremec 2009; Tanaka 2019), Stevens-Johnson syndrome, urticaria (Bock 2014), xeroderma (Cristofanilli 2010)
Endocrine & metabolic: Hypercalcemia (Järhult 2014; Yu 2016), hyperparathyroidism (Järhult 2014)
Hematologic & oncologic: Polycythemia (Kapoor 2019; Yeruva 2015)
Hepatic: Increased serum bilirubin, liver steatosis (Lacey 2014)
Hypersensitivity: Anaphylaxis, angioedema
Infection: Pulmonary cryptococcosis (Wei 2020)
Nervous system: Tardive dyskinesia (Manjunatha 2013)
Neuromuscular & skeletal: Decreased bone mineral density (common: ≥10%) (Eastell 2008; Markopoulos 2010), subacute cutaneous lupus erythematosus (Fisher 2016), tendinopathy (Martens 2007), tenosynovitis (stenosing)
Ophthalmic: Vitreous traction (Eisner 2008)
Hypersensitivity to anastrozole or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy, breastfeeding.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Arimidex: 1 mg
Generic: 1 mg
Yes
Tablets (Anastrozole Oral)
1 mg (per each): $6.94 - $13.50
Tablets (Arimidex Oral)
1 mg (per each): $65.29
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Arimidex: 1 mg
Generic: 1 mg
Oral: May be administered with or without food.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer:
First-line treatment of locally advanced or metastatic breast cancer (hormone receptor–positive or unknown) in postmenopausal patients.
Adjuvant treatment of early hormone receptor-positive breast cancer in postmenopausal patients.
Treatment of advanced breast cancer in postmenopausal patients with disease progression following tamoxifen therapy.
Breast cancer, high-risk, hormone receptor–positive, adjuvant endocrine therapy in premenopausal patients (in combination with ovarian function suppression); Breast cancer in male patients, hormone receptor–positive; Endometrial or uterine cancers (recurrent or metastatic); Ovarian cancer (recurrent); Risk reduction for breast cancer in postmenopausal patients
Anastrozole may be confused with anagrelide, letrozole
Arimidex may be confused with Aromasin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Estrogen Derivatives: May diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Levomethadone: Aromatase Inhibitors may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Methadone: Aromatase Inhibitors may increase the serum concentration of Methadone. Risk C: Monitor therapy
Tamoxifen: May decrease the serum concentration of Anastrozole. Risk X: Avoid combination
Evaluate pregnancy status prior to therapy. Verify the patient is not pregnant prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 3 weeks after the last anastrozole dose.
Based on the mechanism of action and data from animal reproduction studies, anastrozole may cause fetal harm if exposure occurs during pregnancy.
It is not known if anastrozole is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for 2 weeks after the last anastrozole dose.
Hormone-receptor status. Bone mineral density at baseline and periodically thereafter; total cholesterol and LDL. Pregnancy test (prior to treatment in patients who could become pregnant). Monitor adherence.
Breast cancer risk reduction (off-label use): Bone mineral density at baseline, mammograms, and clinical breast exam at baseline and at least every 2 years (Cuzick 2014).
Cardiovascular monitoring for patients with breast cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually in patients with a high 10-year risk (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Anastrozole is a 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.
Onset of estradiol reduction: 70% reduction after 24 hours; 80% after 2 weeks of 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)
Altered kidney function: Renal clearance is decreased proportionally with CrCl and was approximately 50% lower in those with severe renal function impairment (CrCl less than 30 mL/minute per 1.73 m2); this reduced total body clearance by 10%.
Hepatic function impairment: Oral clearance was approximately 30% lower in those with stable hepatic cirrhosis, but plasma concentrations were within normal range.
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