COMMON TRADE NAME(S): Arimidex® (multiple brands available)
In estrogen-dependent tumours, estrogen deprivation causes growth arrest and possibly tumour cell death. Aromatase (estrogen synthetase) is an enzyme that catalyses various steps in the conversion of androgen to estrogen and is found in peripheral tissues as well as breast tumours; peripheral conversion is the major source of estrogens in postmenopausal women. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentration and has no detectable effect on the formation of adrenal corticosteroids, aldosterone, and TSH. Patients with estrogen or progesterone receptor positive tumours are more likely to respond to treatment with aromatase inhibitors. Anastrozole does not have progestogenic, androgenic or estrogenic activity.
Absorption of anastrozole is rapid and maximum plasma level is reached within 2 hours of ingestion. Food decreases the rate but not the overall extent of absorption. Steady state concentration is reached after 7 days of once daily dosing. Pharmacokinetics are linear and do not change with repeated dosing.
Widely distributed into tissues.
|Cross blood brain barrier?||No information found|
Extensively (85%) metabolized in liver (via N-dealkylation, hydroxylation and glucuronidation). No evidence of age or ethnicity effects on pharmacokinetics.
Elimination mainly by metabolism (85%).
- For hormonal treatment of advanced breast cancer in postmenopausal women.
- For the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. Approval is based on superior disease-free survival of anastrozole in comparison to tamoxifen; however, overall survival was not significantly different.
Extravasation Potential: Not applicable
The table below contains adverse effects reported mainly in adjuvant breast cancer with 5-year treatment.
|ORGAN SITE||SIDE EFFECT* (%)||ONSET**|
|Cardiovascular||Arterial thromboembolism (2%)||D|
|Cardiac ischemia (4%)||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|
|Tumour flare (3%) (reported in metastatic breast cancer patients)||E|
|Hepatobiliary||↑ LFTs (rare, may be severe)||D|
|Metabolic / Endocrine||Abnormal electrolyte(s) (↑Ca, rare)||E|
|↑ Cholesterol (9%) (increased HDL 7%)||D|
|Musculoskeletal||Carpal tunnel syndrome (<10%)||E|
|Musculoskeletal pain (36%)||E|
|Osteoporosis (11%) (may be severe)||D|
|Nervous System||Dizziness (8%)||E|
|Mood changes (19%)||D|
|Reproductive and breast disorders||Endometrial cancer (<1%)||D|
|Menopausal symptoms (36%)||E|
|Vaginal bleeding (6%)||E|
|Respiratory||Cough, dyspnea (8%)||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.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
Anastrozole has generally been well tolerated. Most effects are mild or moderate. The most common adverse events are gastrointestinal or musculoskeletal in nature or are expected effects such as hot flashes or vaginal dryness.
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. Joint pain/stiffness and fracture rates were significantly higher in the anastrozole arm
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.
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. Consider calcium and vitamin D supplements in patients taking anastrozole, with the addition of bisphosphonates in patients with existing moderate or high risk fragility fracture/bone mineral density loss. For more information about bone health via dietary and lifestyle measures, see pamphlet on "Bone Health in Post Menopausal Women". Patients should be carefully monitored and treated appropriately.
Recommended treatment duration is 5 years in the adjuvant setting.
No adjustment required
Hold; discontinue if recurs
- Oral self-administration; drug available by outpatient prescription.
- Swallow whole with a glass of water at the same time each day.
- Missed dose should be taken as soon as possible, but only if there are at least 12 hours before the next dose is due.
Anastrozole is contraindicated in patients with hypersensitivity to the drug or any of its components. Estrogen should not be co-administered. 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.
Although anastrozole is non-teratogenic,non-mutagenic and non-clastogenic, it has shown carcinogenic effects, crosses the placenta and is fetotoxic. It is contraindicated in pregnant or lactating women. Anastrozole is not recommended for use in premenopausal women as safety and efficacy have not been established.
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.
|Tamoxifen||↓ anastrozole concentration (by 27%)||Unknown||Do not co-administer since no efficacy or safety benefit.|
|Estrogen-containing herbals, estrogen||↓ estrogen suppression||Avoid|
|Monitor Type||Monitor Frequency|
|Bone mineral density for patients at risk||Baseline and routine|
|Clinical toxicity assessment for fatigue, musculoskeletal, estrogen withdrawal symptoms, rash, edema, thromboembolism, cardiovascular, GI and GU effects, etc.||Baseline and routine|
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
|Monitor Type||Monitor Frequency|
|Cholesterol and lipid evaluation||baseline and regular|
|Electrolytes, including calcium||baseline and as clinically indicated|
|Liver function tests||baseline and as clinically indicated|
ODB Limited Use (
- anastrozole - For the treatment of metastatic breast cancer in hormone receptor positive post-menopausal women ()
- anastrozole - An alternative to tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor positive breast cancer ()
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 4, 2013.
October 2017 Added public funding info; revised Feb 2013
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