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Anastrozole

Medically reviewed by Drugs.com. Last updated on Aug 29, 2020.

Pronunciation

(an AS troe zole)

Index Terms

  • ICI-D1033
  • ZD1033

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Arimidex: 1 mg

Generic: 1 mg

Brand Names: U.S.

  • Arimidex

Pharmacologic Category

  • Antineoplastic Agent, Aromatase Inhibitor

Pharmacology

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.

Absorption

Well absorbed; extent of absorption not affected by food

Metabolism

Extensively hepatic (~85%) via N-dealkylation, hydroxylation, and glucuronidation; primary metabolite (triazole) inactive

Excretion

Feces; urine (urinary excretion accounts for ~10% of total elimination, mostly as metabolites)

Onset of Action

Onset of estradiol reduction: 70% reduction after 24 hours; 80% after 2 weeks of therapy

Time to Peak

Plasma: ~2 hours without food; 5 hours with food

Duration of Action

Duration of estradiol reduction: 6 days

Half-Life Elimination

~50 hours

Protein Binding

Plasma: 40%

Special Populations: 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%.

Special Populations: Hepatic Function Impairment

Oral clearance was approximately 30% lower in those with stable hepatic cirrhosis, but plasma concentrations were within normal range.

Use: Labeled Indications

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

Off Label Uses

Endometrial or uterine cancers (recurrent or metastatic)

Hormonal agents such as progestational agents or tamoxifen may be used in the management of recurrent or metastatic endometrial cancer; in select patients, aromatase inhibitors, including anastrozole, may be considered. A small phase II trial evaluated anastrozole in a group of unselected patients with advanced recurrent or persistent endometrial cancer; the results showed minimal activity of anastrozole [Rose 2000]. A retrospective analysis of patients with uterine leiomyosarcoma suggests that, in patients with low disease burden and an indolent course (who are estrogen- or progesterone-receptor positive), hormone blockade with an aromatase inhibitor such as anastrozole may be considered [O'Cearbhaill 2010].

Ovarian cancer (recurrent)

Hormonal therapy, including aromatase inhibitors such as anastrozole, may be considered in patients with recurrent ovarian cancer who cannot tolerate or have not responded to other chemotherapy regimens. Data from a small phase II study in patients with ovarian cancer suggests that anastrozole may lead to a response in a small number of patients, and is well tolerated [del Carmen 2003].

Risk reduction for breast cancer in postmenopausal women

Data from a large international, randomized, placebo-controlled, double-blind phase III study (IBIS-II) support the use of anastrozole in the prevention of breast cancer in high-risk postmenopausal women [Cuzick 2014].

Contraindications

Hypersensitivity to anastrozole or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy, breastfeeding

Dosing: Adult

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.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: May be administered with or without food.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Estrogen Derivatives: May diminish the therapeutic effect of Anastrozole. Avoid combination

Levomethadone: Aromatase Inhibitors may increase the serum concentration of Levomethadone. Monitor therapy

Methadone: Aromatase Inhibitors may increase the serum concentration of Methadone. Monitor therapy

Tamoxifen: May decrease the serum concentration of Anastrozole. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Comparator: Tamoxifen

>10%:

Cardiovascular: Angina pectoris (2% [comparator: 1.6%]; 12% [comparator: 5.2%] in patients with preexisting ischemic heart disease), hypertension (5% to 13%), ischemic heart disease (4% [comparator: 3%]; increased incidence of ischemic cardiovascular events seen in patients with preexisting ischemic heart disease: 17% [comparator: 10%]), vasodilation (25% to 36%)

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% [comparator: 11%]; literature suggests incidence as high as 36%) (Howell 2005), arthritis (17% [comparator: 14%]), asthenia (≤19%), back pain (10% to 12% [comparator: 10% to 13%]), ostealgia (7% to 11% [comparator: 6% to 10%]), osteoporosis (11% [comparator: 7%]; literature suggests incidence as high as 20% in patients with preexisting osteopenia after 3- to 6-years of anastrazole) (van Hellemond 2019)

Respiratory: Increased cough (8% to 11%), pharyngitis (6% to 14%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (1% [comparator: 1.1%]; 1% [comparator: 3.2%] in patients with preexisting ischemic heart disease), 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%)

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% [comparator: 0.7%]), 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%)

Neuromuscular & skeletal: Arthropathy (6% to 7% [comparator: 5%]), bone fracture (1% to 10% [comparator: 1% to 7%]), myalgia (6% [comparator: 5%]), neck pain (2% to 5%), pathological fracture (2% to 5%)

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), tendon disease (Martens 2007), tenosynovitis (stenosing)

Ophthalmic: Vitreous traction (Eisner 2008)

Warnings/Precautions

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) in postmenopausal females; decreases (from baseline) in total hip and lumbar spine BMD have been reported. Patients with preexisting osteopenia are at higher risk for developing osteoporosis (Eastell 2008). When initiating anastrozole treatment, monitor BMD at baseline and periodically thereafter. Lifestyle modifications (including exercise, smoking cessation, decreased alcohol intake) and adequate vitamin D and calcium intake are recommended. Bone-modifying agents may be useful in patients at risk for fractures (ASCO [Shapiro 2019]).

• Hypercholesterolemia: Elevated total cholesterol levels (contributed to by low-density lipoprotein [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.

• Hypersensitivity: Allergic reactions, including anaphylaxis, angioedema, and urticaria, have been reported.

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 preexisting ischemic cardiac disease have an increased risk for ischemic cardiovascular events.

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]).

Monitoring Parameters

Bone mineral density; 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)

Reproductive Considerations

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.

Pregnancy Considerations

Based on the mechanism of action and information from animal reproduction studies, anastrozole may cause fetal harm if exposure occurs during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat breast cancer in women after change of life.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hot flashes

• Loss of strength and energy

• Weight gain

• Anxiety

• Sweating a lot

• Flu-like symptoms

• Dry mouth

• Pelvic pain

• Constipation

• Diarrhea

• Nausea

• Vomiting

• Joint pain

• Joint swelling

• Muscle pain

• Trouble sleeping

• Cough

• Sore throat

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.

• Shortness of breath

• Swelling of arms or legs

• Severe headache

• Burning or numbness feeling

• Swollen glands

• Bone pain

• Chest pain

• Mood changes

• Depression

• Severe dizziness

• Passing out

• Vision changes

• Breast pain

• Abnormal vaginal bleeding

• Vaginal pain, itching, and discharge

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions