You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Get the latest updates or take a self-assessment.

Chemotherapy and other systemic treatment regimens may change due to COVID-19. Find out more at Systemic Treatment Regimens During COVID-19.

A - Drug Name

anastrozole

COMMON TRADE NAME(S):   Arimidex®

 
B - Mechanism of Action and Pharmacokinetics

Anastrozole is a potent and selective non-steroidal aromatase inhibitor which significantly lowers serum estradiol concentration. It does not have progestogenic, androgenic or estrogenic activity. In estrogen-dependent tumours, estrogen deprivation causes growth arrest and possibly tumour cell death. Anastrozole has no detectable effect on the formation of adrenal corticosteroids, aldosterone, and TSH.



Absorption

Absorption of anastrozole is rapid and maximum plasma level is reached within 2 hours of ingestion under fasting. Pharmacokinetics are linear and do not change with repeated dosing.

Bioavailability

80%

Effects with food

Food decreases rate but not overall extent of absorption.

Time to reach steady state

7 days


Distribution

Widely distributed into tissues.

PPB 40%
Metabolism

Extensively (85%) metabolized in liver (via N-dealkylation, hydroxylation and glucuronidation).

Active metabolites No
Inactive metabolites Yes
Elimination

Elimination mainly by metabolism (85%).

Urine

11% (unchanged), and other metabolites

Half-life 50 hours
 
C - Indications and Status
Health Canada Approvals:

  • For hormonal treatment of advanced breast cancer in postmenopausal women.
  • For the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.*

Notes:

*Marketing approval is based on superior disease-free survival of anastrozole in comparison to tamoxifen; however, overall survival was not significantly different.



Other Uses:

  • Endometrial cancer
 
D - Adverse Effects

Emetogenic Potential:  

Not applicable

The table below contains adverse effects reported mainly in adjuvant breast cancer with 5-year treatment. It also includes severe, life-threatening, or post-marketing adverse events from other sources.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Arterial thromboembolism (2%) D
Cardiac ischemia (4%) E
Hypertension (13%) D
Lymphedema (10%) E
Venous thromboembolism (3%) D
Dermatological Rash (11%) (may be severe) E
Gastrointestinal Abdominal pain (9%) I  E
Nausea, vomiting (13%) I  E
Weight changes (9%) D
General Fatigue (19%) E
Tumour flare (3%) (reported in metastatic breast cancer patients) E
Hematological Anemia (4%) D
Leukopenia (<5%) D
Hepatobiliary ↑ LFTs (<5%) (may be severe) D
Hypersensitivity Hypersensitivity (rare) I
Infection Infection (9%) E
Metabolic / Endocrine Abnormal electrolyte(s) (↑Ca, rare) E
↑ Cholesterol (9%) (increased HDL 7%) D
Musculoskeletal Carpal tunnel syndrome (<10%) E
Fracture (10%) D
Musculoskeletal pain (36%) E
Osteoporosis (11%) (may be severe) D
Nervous System Dizziness (8%) E
Dysgeusia (rare) E
Headache (10%) E
Insomnia (10%) E
Mood changes (19%) D
Paresthesia (7%) E
Ophthalmic Cataract (6%) D
Reproductive and breast disorders Endometrial cancer (<1%) D
Estrogen deprivation symptoms (36%) E
Vaginal bleeding (6%) E
Respiratory Cough, dyspnea (8%) E
Vascular Vasculitis (rare) E


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common side effects for anastrozole include estrogen deprivation symptoms, musculoskeletal pain, fatigue, mood changes, hypertension, nausea, vomiting, osteoporosis, rash, fracture and headache.

Patients treated with aromatase inhibitors may be at a higher risk for cardiovascular events (especially in patients with pre-existing ischemic heart disease) as well as osteoporosis.

Joint pain/stiffness was reported with an incidence of 36% (compared to 29% in patients on tamoxifen); arthritis alone was reported with an incidence of 17%. The use of aromatase inhibitors may cause arthralgia/arthritis, which may impact on treatment compliance and quality of life.

In phase III studies comparing anastrozole versus megestrol acetate as second-line endocrine therapy for advanced breast cancer, the incidence of gastrointestinal symptoms, hot flashes, vaginal dryness and thromboembolic disease were similar among anastrozole and megestrol recipients. However, more patients treated with megestrol acetate reported weight gain as an adverse event compared to patients treated with anastrozole.

Anastrozole had statistically significant lower incidences of hot flashes, vaginal bleeding/discharge, endometrial cancer, venous thromboembolism, and ischemic cerebrovascular events than tamoxifen. 

In the pivotal phase III trial comparing anastrozole and tamoxifen for adjuvant breast cancer, fracture rates were higher in the anastrozole group while on active treatment, but were not different after treatment completion.  

 
E - Dosing

Refer to protocol by which patient is being treated.

Assess patient’s risk factors for osteoporosis and consider calcium and vitamin D supplements and bisphosphonates where appropriate. Refer patients to the Bone Health During Cancer Treatment pamphlet for more information.



Adults:

Oral: 1 mg Daily

Dosage with Toxicity:

 

Toxicity Action
Myelosuppression No adjustment required.
Severe hypercalcemia Hold; discontinue if recurs.


Dosage with Hepatic Impairment:

Clearance is reduced by 30% in patients with cirrhosis, but plasma levels are within normal range.

Hepatic Impairment Anastrozole Dose
Mild to Moderate No adjustment is required.
Severe Not studied; consider potential risk/benefit.


Dosage with Renal Impairment:

Clearance is reduced by 50% in severe renal impairment. However, renal excretion is a minor route of excretion and no adjustment is required.

Creatinine Clearance (mL/min) Anastrozole Dose
> 30 No adjustment is required.
< 30 No adjustment is required. Consider potential risk/benefit.


Dosage in the elderly:

No dosage adjustment required.



Dosage based on ethnicity:

No dose adjustment is required. No clinically significant differences in pharmacokinetics and therapeutic responses were observed in Japanese and Caucasian patients. 



Children:

Not recommended for use as safety and efficacy have not been established.



 
F - Administration Guidelines

  • Administer anastrozole with or without food.
  • Tablets should be swallowed whole with a glass of water at the same time each day.
  • Missed doses should be taken as soon as possible, but only if there are at least 12 hours before the next dose is due.
  • Store at room temperature (15 to 30°C).


 
G - Special Precautions
Contraindications:

  • Patients with hypersensitivity to the drug or any of its components
  • Pregnant or lactating women

Other Warnings/Precautions:

  • Use is not recommended in pre-menopausal women*.
  • Use with caution in patients with known osteoporosis or risk factors for osteoporosis, in patients with pre-existing cardiovascular disorders, severe liver or renal impairment.
  • Anastrozole has not been studied in patients with brain, leptomeningeal or pulmonary lymphangitic disease.
  • Use of formulations containing lactose should be carefully considered in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

*not receiving ovarian suppression


Other Drug Properties:

  • Carcinogenicity: Unknown

    Animal studies revealed increased incidences of various malignancies in both male and female populations; a non-genotoxic mechanims may play a role.

Pregnancy and Lactation:
  • Teratogenicity: No
  • Mutagenicity: No
  • Clastogenicity: No
  • Fetotoxicity: Yes

    Anastrozole is contraindicated in pregnancy. Adequate contraception must be used by both sexes during treatment, and for at least 6 months (general recommendation) after the last dose.

  • Lactation: Contraindicated
  • Fertility effects: Probable

    Anastrozole increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption and decreased numbers of live fetuses) and produced high incidence of infertility in animal studies.

 
H - Interactions

Antipyrine, cimetidine, tamoxifen and warfarin clinical interaction studies indicate that the co-administration of anastrozole with other drugs is unlikely to result in clinically significant CYP450 drug interactions. In clinical studies, there was no evidence of an interaction when anastrozole is co-administered with warfarin or bisphosphonates.

AGENT EFFECT MECHANISM MANAGEMENT
Tamoxifen ↓ anastrozole concentration (by 27%) Unknown Do not co-administer since no efficacy or safety benefit.
Estrogen-containing or estrogenic agents ↓ estrogen suppression Avoid.
 
I - Recommended Clinical Monitoring
Recommended Clinical Monitoring

Monitor Type Monitor Frequency

Bone mineral density for patients at risk

Baseline and as clinically indicated

Clinical toxicity assessment for fatigue, musculoskeletal, estrogen deprivation symptoms, rash, edema, thromboembolism, cardiovascular, GI and GU effects

At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version



Suggested Clinical Monitoring

Monitor Type Monitor Frequency

Liver function tests

Baseline and as clinically indicated

Electrolytes, including calcium

Baseline and as clinically indicated

Cholesterol and lipid evaluation

Baseline and as clinically indicated
 
J - Supplementary Public Funding

ODB - General Benefit (ODB Formulary )

  • anastrozole

 
K - References

ATAC Trialists Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncology 2008; 9(1): 45-53.

ATAC Trialists' Group. 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. McEvoy GK, editor.

AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists, p. 918-23.

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. Arimidex Study Group. J Clin Oncol 2000 Nov 15;18(22):3758-67.

Product Monograph: Arimidex® (anastrozole). AstraZeneca Canada, January 19, 2018.


November 2020 Updated dosing and monitoring sections

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.