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anastrozole
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 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 |
Widely distributed into tissues.
| PPB | 40% |
Extensively (85%) metabolized in liver (via N-dealkylation, hydroxylation and glucuronidation).
| Active metabolites | No |
| Inactive metabolites | Yes |
Elimination mainly by metabolism (85%).
| Urine |
11% (unchanged), and other metabolites |
| Half-life | 50 hours |
- Breast cancer
Refer to the product monograph for a full list and details of approved indications.
Other Uses:
- Endometrial cancer
Emetogenic Potential:
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 | Erythema multiforme (rare) | E | |||
| Rash (11%) | E | ||||
| Stevens-Johnson syndrome (rare) | 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%) (including depression) | 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.
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.
| Toxicity | Action |
| Myelosuppression | No adjustment required. |
| Severe hypercalcemia | Hold; discontinue if recurs. |
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. |
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. |
No dosage adjustment required.
No dose adjustment is required. No clinically significant differences in pharmacokinetics and therapeutic responses were observed in Japanese and Caucasian patients.
Not recommended for use as safety and efficacy have not been established.
- 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).
- Patients with hypersensitivity to the drug or any of its components
- Pregnant or lactating women
- 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.
-
Teratogenicity:
No
-
Mutagenicity:
No
-
Clastogenicity:
No
-
Fetotoxicity:
Yes
Anastrozole is contraindicated in pregnancy. Adequate contraception must be used by patients and their partners 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.
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. |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| 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, mood changes (including depression), 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
| 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 |
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, June 30 ,2021.
April 2024 Updated Pregnancy and Lactation section
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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