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Overview
| Generic Names: | Anastrozol; anastrozole |
|---|---|
| Trade Names: | Anastrole; Arimidex |
| PharmGKB Accession Id: | PA448432 |
Description
Anastrozole is a drug indicated in the treatment of breast cancer in post-menopausal women. It is used both in adjuvant therapy (i.e. following surgery) and in metastatic breast cancer. It decreases the amount of estrogens that the body makes. Anastrozole belongs in the class of drugs known as aromatase inhibitors. It inhibits the enzyme aromatase, which is responsible for converting androgens (produced by women in the adrenal glands) to estrogens. (source: Drug Bank)
Indication
For treatment of breast cancer in post-menopausal women. (source: Drug Bank)
ATC Therapeutic Category
- L02BG:Enzyme inhibitors
Pharmacology, Interactions, and Contraindications
Mechanism Of Action
Anastrozole selectively inhibits aromatase. The principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues. Therefore, aromatase inhibition leads to a decrease in circulatin estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. (source: Drug Bank)
Pharmacology
Anastrozole is a potent and selective non-steroidal aromatase inhibitor indicated for the treatment of advanced breast cancer in post-menopausal women with disease progression following tamoxifen therapy. Many breast cancers have estrogen receptors and growth of these tumors can be stimulated by estrogens. In post-menopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue, with further conversion of estrone to estradiol. Many breast cancers also contain aromatase; the importance of tumor-generated estrogens is uncertain. Treatment of breast cancer has included efforts to decrease estrogen levels by ovariectomy premenopausally and by use of anti-estrogens and progestational agents both pre- and post-menopausally, and these interventions lead to decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. (source: Drug Bank)
Food Interactions
Food decreases the rate of absorption, but the extent of absorption is not affected. (source: Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole. (source: Drug Bank)
Protein Binding
40% (source: Drug Bank)
Absorption
Well absorbed into the systemic cirulation following oral administration. Food does not affect the extent of absorption. (source: Drug Bank)
Toxicity
In rats, lethality is greater than 100 mg/kg. (source: Drug Bank)
Isomeric SMILES Code:
CC(C)(C#N)c1cc(cc(c1)C(C)(C)C#N)Cn2cncn2 (source: Drug Bank)
Curated Annotations (
)
-
rs6493497
at chr15:49418127
in
CYP19A1
Phenotype: This SNP, along with a second one in tight LD (rs71760050) was significantly associated, in a cohort of estrogen-receptor-positive patients with primary breast cancer larger than 3 cm, with change in aromatase activity before and after aromatase inhibitor neoadjuvant treatment . It was also associated, but not significantly so after adjustment for multiple testing, with change in estrone level and with pretreatment aromatase level. Study size: 45. Study population/ethnicity: Edinburgh female ER-positive patients, primary breast cancer larger than 3 cm. Significance metric(s): nominal p = 0.0063, p = 0.039 after adjustment for multiple testing. Type of association: PD; GN;FA. Second Phenotype: In a group of 200 women with early-stage breast cancer, who were treated with 1 mg/day adjuvant anastrozole, this SNP was significantly associated with pre-drug and post-drug estradiol plasma concentrations after adjusting for plasma anastrozole concentrations. Study size: 200. Study population: women with early-stage breast cancer (Mayo Clinic-M.D. Anderson pharmacogenomic study participants) . Significance metric(s):pre-drug p = 0.028; post-drug p = 0.0002. Type of association: PD; GN;FA- Related Drugs:
- anastrozole, exemestane, letrozole
- Related Diseases:
- Breast Neoplasms
- Evidence:
-
PMID:20048079
-
rs7176005
at chr15:49418571
in
CYP19A1
Phenotype: This SNP, along with a second one in tight LD (rs6493497) was significantly associated, in a cohort of estrogen-receptor-positive patients with primary breast cancer larger than 3 cm, with change in aromatase activity before and after aromatase inhibitor neoadjuvant treatment . It was also associated, but not significantly so after adjustment for multiple testing, with change in estrone level and with pretreatment aromatase level. Study size: 45. Study population/ethnicity: Edinburgh female ER-positive patients, primary breast cancer larger than 3 cm. Significance metric(s): nominal p = 0.0063, p = 0.039 after adjustment for multiple testing. Type of association: PD; GN;FA. Second Phenotype: In a group of 200 women with early stage breast cancer, who were treated with 1 mg/day adjuvant anastrozole, this SNP was significantly associated with pre-drug and post-drug estradiol plasma concentrations after adjusting for plasma anastrozole concentrations. Study size: 200. Study population: women with early stage breast cancer (Mayo Clinic-M.D. Anderson pharmacogenomic study participants) . Significance metric(s):pre-drug p = 0.057; post-drug p = 0.0002. Type of association: PD; GN;FA- Related Drugs:
- anastrozole, exemestane, letrozole
- Related Diseases:
- Breast Neoplasms
- Evidence:
-
PMID:20048079
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
|
CYP19A1 |
|
Publications, Variants |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| CYP19A1 |
|
(source: Drug Bank) |
PharmGKB Curated Pathways
The following drugs are in curated knowledge about this drug.
| Drug | Relationship | Evidence | |
|---|---|---|---|
|
|
conjugated estrogens |
|
Publications |
|
|
estradiol |
|
Publications |
|
|
estrone |
|
Publications |
|
|
tamoxifen |
|
Publications |
|
|
testosterone |
|
Publications |
A list of non-curated publications that mention this drug along with other drugs is available.
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Breast Neoplasms |
|
Publications, Variants |
|
|
Neoplasms |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
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Non-Curated Publications
A list of non-curated publications that mention this drug is available.
