Breast cancer, advanced: Postmenopausal females: Oral: 1 mg once daily; continue until tumor progression.
Breast cancer, advanced, estrogen receptor-positive, HER2-negative (off-label combination):
Postmenopausal females: Oral: 1 mg once daily (in combination with abemaciclib) until disease progression or unacceptable toxicity (Goetz 2017).
Premenopausal or perimenopausal females: Oral: 1 mg once daily (in combination with ribociclib [and the luteinizing hormone-releasing hormone (LHRH) agonist goserelin]) until disease progression or unacceptable toxicity (Tripathy 2018).
Breast cancer, early (adjuvant treatment): Postmenopausal females: Oral: 1 mg once daily.
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 maximum duration of 5 years of aromatase inhibitor (AI) therapy for postmenopausal women; AIs may be combined with tamoxifen for a total duration of up to 10 years of endocrine therapy. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Burstein 2014). In a phase III 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 (Goss 2016). The decision to extend aromatase inhibitor therapy for an additional 5 years should include initial adjuvant therapy (tamoxifen versus an aromatase inhibitor) and an assessment of the risk of recurrence.
Breast cancer, risk reduction (off-label use): Postmenopausal females ≥40 years of age: Oral: 1 mg once daily for 5 years (Cuzick 2014).
Endometrial or uterine cancer, recurrent or metastatic (off-label use): Oral: 1 mg once daily (Rose 2000).
Ovarian cancer, recurrent (off-label use): Oral: 1 mg once daily until disease progression or unacceptable toxicity (del Carmen 2003).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
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 (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Arimidex: 1 mg
Generic: 1 mg
Yes
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, 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 women
Adjuvant treatment of early hormone receptor-positive breast cancer in postmenopausal women
Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy
Endometrial or uterine cancers (recurrent or metastatic); Ovarian cancer (recurrent); Risk reduction for breast cancer in postmenopausal women
Anastrozole may be confused with anagrelide, letrozole
Arimidex may be confused with Aromasin
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 hormone replacement 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. Has not been studied in patients with severe hepatic impairment.
Special populations:
• Premenopausal females: Aromatase inhibitors (including anastrozole) should not be used as monotherapy in premenopausal females with breast cancer (Puhalla 2009). Premenopausal females with metastatic breast cancer should be offered ovarian suppression or ablation along with hormonal therapy (ASCO [Rugo 2016]).
None known.
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. Females of reproductive potential should use effective contraception during therapy and for at least 3 weeks after the last anastrozole dose.
Based on the mechanism of action and information 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.
Bone mineral density at baseline and periodically thereafter; total cholesterol and LDL. Pregnancy test (prior to treatment in females of reproductive potential). 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)
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)
Renal function impairment: 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.
Tablets (Anastrozole Oral)
1 mg (per each): $6.94 - $13.50
Tablets (Arimidex Oral)
1 mg (per each): $65.29
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