Identification

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Name
Anastrozole
Accession Number
DB01217  (APRD00016)
Type
Small Molecule
Groups
Approved, Investigational
Description

Anastrozole is a non-steroidal aromatase inhibitor (AI), similar to letrozole, used to decrease circulating estrogen levels in the treatment of postmenopausal women with estrogen-responsive breast cancer.10 Anastrozole is also related to exemestane, a steroidal AI, but its non-steroidal nature provides stark advantages including a lack of steroid-associated adverse effects such as weight gain and acne.4 Aromatase inhibitors, including anastrozole, have become endocrine drugs of choice in the treatment of postmenopausal breast cancer due to a more favourable efficacy and adverse effect profile as compared to earlier estrogen receptor modulators such as tamoxifen.5,8

Anastrozole was first approved for use in the United States in 1995.10

Structure
Thumb
Synonyms
  • Anastrozol
  • Anastrozole
  • α,α,α',α'-Tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile
External IDs
ICI D1033 / ICI-D1033 / ZD-1033 / ZD1033
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act AnastrozoleTabletOralTEVA Canada Limited2012-10-25Not applicableCanada
AnastrozoleTablet, film coated1 mg/1OralGlobal Pharmaceuticals2013-06-052013-08-26Us
AnastrozoleTablet1 mgOralSanis Health Inc2015-07-22Not applicableCanada
AnastrozoleTablet, coated1 mg/1OralBoscogen, Inc.2011-03-31Not applicableUs
AnastrozoleTabletOralPro Doc Limitee2012-11-22Not applicableCanada
ArimidexTablet1 mg/1OralPhysicians Total Care, Inc.2004-02-19Not applicableUs
ArimidexTablet1 mg/1OralANI Pharmaceuticals, Inc.2018-06-26Not applicableUs
ArimidexTablet1 mg/1OralAstraZeneca Pharmaceuticals LP1996-01-162019-06-30Us
Arimidex Tab 1mgTabletOralAstra Zeneca1996-08-30Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-anastrozole TabletsTabletOralAccel Pharma IncNot applicableNot applicableCanada
Ach-anastrozoleTabletOralAccord Healthcare Inc2012-10-25Not applicableCanada
AnastrozoleTablet1 mg/1OralRebel Distributors2010-06-28Not applicableUs
AnastrozoleTablet, film coated1 mg/1OralMylan Pharmaceuticals2010-06-282013-12-31Us
AnastrozoleTablet1 mg/1OralYiling Pharmaceutical, Inc.2019-02-28Not applicableUs
AnastrozoleTablet1 mg/1OralPhysicians Total Care, Inc.2010-07-01Not applicableUs
AnastrozoleTablet1 mg/1OralWest-Ward Pharmaceuticals Corp.2010-06-282018-03-08Us
AnastrozoleTablet, coated1 mg/1OralBluePoint Laboratories2014-01-01Not applicableUs
AnastrozoleTablet, film coated1 mg/1OralMylan Institutional2010-06-112013-09-30Us
AnastrozoleTablet, coated1 mg/1OralZydus Pharmaceuticals (USA) Inc.2010-06-27Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Testosterone / AnastrozoleAnastrozole (20 mg/1) + Testosterone (200 mg/1)PelletOralQualgen Llc2017-11-142018-05-21Us
International/Other Brands
Asiolex
Categories
UNII
2Z07MYW1AZ
CAS number
120511-73-1
Weight
Average: 293.3663
Monoisotopic: 293.164045633
Chemical Formula
C17H19N5
InChI Key
YBBLVLTVTVSKRW-UHFFFAOYSA-N
InChI
InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3
IUPAC Name
2-[3-(1-cyano-1-methylethyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]phenyl]-2-methylpropanenitrile
SMILES
CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N

Pharmacology

Indication

Anastrozole is indicated as adjunct therapy in the treatment of hormone receptor-positive early breast cancer in postmenopausal women, and as a first-line treatment for hormone receptor-positive (or hormone receptor-unknown) locally advanced or metastatic breast cancer in postmenopausal women.10 It may also be used in the treatment of advanced breast cancer in postmenopausal women who experience disease progression despite treatment with tamoxifen.11,10

Associated Conditions
Pharmacodynamics

Anastrozole prevents the conversion of adrenal androgens (e.g. testosterone) to estrogen in peripheral and tumour tissues. As the growth of many breast cancers is stimulated and/or maintained by the presence of estrogen, anastrozole helps to treat these cancers by decreasing the levels of circulating estrogens.12,9 Anastrozole has a relatively long duration of action allowing for once daily dosing - serum estradiol is reduced by approximately 70% within 24 hours of beginning therapy with 1mg once daily, and levels remain suppressed for up to 6 days following cessation of therapy.10

The incidence of ischemic cardiovascular events was increased during anastrozole therapy and patients with pre-existing ischemic heart disease should consider the risks and benefits of anastrozole before beginning therapy. Anastrozole has also been reported to decrease spine and hip bone mineral density (BMD), so consideration should be given to monitoring of BMD in patients receiving long-term therapy.10,8

Mechanism of action

Anastrazole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues.5 Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone.10 In postmenopausal women, estrogen is primarily derived from the conversion of adrenally-produced androgens into estrogens by the aromatase enzyme - by competitively inhibiting the biosynthesis of estrogen at these enzymes, anastrozole effectively suppresses circulating estrogen levels and, subsequently, the growth of hormone receptor-positive tumours.5,9

TargetActionsOrganism
ACytochrome P450 19A1
inhibitor
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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Absorption

Anastrozole is rapidly absorbed and Tmax is typically reached within 2 hours of dosing under fasted conditions.5,12 Coadministration with food reduces the rate but not the overall extent of absorption - mean Cmax decreased by 16% and the median Tmax was extended to 5 hours when anastrozole was administered 30 minutes after ingestion of food,10 though this relatively minor alteration in absorption kinetics is not expected to result in clinically significant effects.11

Volume of distribution

The volume of distribution of anastrozole into brain tissue in mice is 3.19 mL/g. Distribution into the CNS is limited due to the activity of P-gp efflux pumps at the blood brain barrier, of which anastrozole is a substrate.2

Protein binding

Anastrozole is 40% protein bound in plasma10 and appears to be independent of plasma concentration.12

Metabolism

Anastrozole is primarily metabolized in the liver via oxidation and glucuronidation to a number of inactive metabolites, including hydroxyanastrozole (both free and glucuronidated) and anastrozole glucuronide.1,10,12 Oxidation to hydroxyanastrozole is catalyzed predominantly by CYP3A4 (as well as CYP3A5 and CYP2C8, to a lesser extent) and the direct glucuronidation of anastrozole appears to be catalyzed mainly by UGT1A4.1

Anastrozole may also undergo N-dealkylation to form triazole and 3,5-Bis-(2-methylpropiononitrile)-benzoic acid.1 Labels for anastrozole state the main metabolite found in plasma following administration is triazole,10,12 but a recent pharmacokinetic study was unable to detect any products of N-dealkylation in vitro.1

Route of elimination

Hepatic metabolism accounts for approximately 85% of anastrozole elimination.10 Approximately 10% of the administered dosage is eliminated unchanged in the urine.12,13

Half life

The elimination half-life of anastrozole is approximately 50 hours.10,12,5

Clearance

Anastrozole's clearance is mainly via hepatic metabolism and can therefore be altered in patients with hepatic impairment - patients with stable hepatic cirrhosis exhibit an apparent oral clearance approximately 30% lower compared with patients with normal liver function.10,12 Conversely, renal impairment has a negligible effect on total drug clearance as the renal route is a relatively minor clearance pathway for anastrozole. In volunteers with severe renal impairment, renal clearance was reduced by 50% while total clearance was only reduced by approximately 10%.10,12

Toxicity

The reported oral TDLo in a human woman is 1.68 mg/kg given intermittently over the course of 12 weeks.14 Knowledge of the signs and symptoms of anastrozole overdose is incomplete as there are no documented descriptions of a patient receiving more than 60mg,13 a dose which was administered to a healthy male volunteer and was well-tolerated.10,12 There is no antidote for anastrozole and treatment should be supportive and symptomatic, including close monitoring of patient vital signs. As anastrozole exhibits relatively low protein binding, dialysis may be helpful and should be considered in select cases.10,12

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Anastrozole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Anastrozole.
AbataceptThe metabolism of Anastrozole can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Anastrozole can be increased when it is combined with Abemaciclib.
AbirateroneThe metabolism of Anastrozole can be decreased when combined with Abiraterone.
AcebutololThe serum concentration of Anastrozole can be increased when it is combined with Acebutolol.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Anastrozole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Anastrozole.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Anastrozole.
Acetylsalicylic acidThe serum concentration of Anastrozole can be increased when it is combined with Acetylsalicylic acid.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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Food Interactions
  • Food decreases the rate of absorption, but the extent of absorption is not affected.

References

Synthesis Reference

Anil Khile, Narendra Joshi, Shekhar Bhirud, "Process for the preparation of anastrozole and intermediates thereof." U.S. Patent US20060189670, issued August 24, 2006.

US20060189670
General References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
  2. Miyajima M, Kusuhara H, Takahashi K, Takashima T, Hosoya T, Watanabe Y, Sugiyama Y: Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system. J Pharm Sci. 2013 Sep;102(9):3309-19. doi: 10.1002/jps.23600. Epub 2013 May 27. [PubMed:23712697]
  3. Gervasini G, Jara C, Olier C, Romero N, Martinez R, Carrillo JA: Polymorphisms in ABCB1 and CYP19A1 genes affect anastrozole plasma concentrations and clinical outcomes in postmenopausal breast cancer patients. Br J Clin Pharmacol. 2017 Mar;83(3):562-571. doi: 10.1111/bcp.13130. Epub 2016 Oct 18. [PubMed:27747906]
  4. Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM: An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Cancer. 2002 Nov 1;95(9):2006-16. doi: 10.1002/cncr.10908. [PubMed:12404296]
  5. Barros-Oliveira MDC, Costa-Silva DR, Andrade DB, Borges US, Tavares CB, Borges RS, Silva JM, Silva BBD: Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review. Rev Assoc Med Bras (1992). 2017 Apr;63(4):371-378. doi: 10.1590/1806-9282.63.04.371. [PubMed:28614542]
  6. Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [PubMed:9152599]
  7. Kelly CM, Buzdar AU: Anastrozole. Expert Opin Drug Saf. 2010 Nov;9(6):995-1003. doi: 10.1517/14740338.2010.515977. [PubMed:20923259]
  8. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. doi: 10.1016/S1470-2045(10)70257-6. Epub 2010 Nov 17. [PubMed:21087898]
  9. Gobbi S, Rampa A, Belluti F, Bisi A: Nonsteroidal aromatase inhibitors for the treatment of breast cancer: an update. Anticancer Agents Med Chem. 2014 Jan;14(1):54-65. [PubMed:23869785]
  10. FDA Approved Drugs: Anastrozole [Link]
  11. EMA Approved Drugs: Anastrozole [Link]
  12. DPD Approved Drugs: Anastrozole [Link]
  13. Medsafe NZ: Anastrozole [Link]
  14. CaymenChem: Anastrozole MSDS [Link]
External Links
Human Metabolome Database
HMDB0015348
KEGG Drug
D00960
KEGG Compound
C08159
PubChem Compound
2187
PubChem Substance
46504987
ChemSpider
2102
BindingDB
10015
ChEBI
2704
ChEMBL
CHEMBL1399
Therapeutic Targets Database
DAP000627
PharmGKB
PA448432
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Anastrozole
ATC Codes
L02BG03 — Anastrozole
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnBasic ScienceHigh Blood Pressure (Hypertension)1
1Active Not RecruitingTreatmentCancer, Advanced / Tumors, Solid1
1Active Not RecruitingTreatmentCancer, Breast / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedNot AvailableCancer, Breast1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceNormal Healthy Volunteers2
1CompletedBasic ScienceTumors, Solid1
1CompletedDiagnosticEndometriosis1
1CompletedPreventionMammographic Density1
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentEstrogen Receptor Positive / Invasive Breast Carcinoma / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentMammographic Density1
1CompletedTreatmentPharmacokinetics / Safety1
1Not Yet RecruitingTreatmentAnatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Anatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v8 / Prognostic Stage IV Breast Cancer AJCC v8 / Recurrent Breast Carcinoma1
1RecruitingTreatmentNeoplasms, Breast1
1RecruitingTreatmentNeoplasms / Neoplasms, Breast1
1TerminatedBasic ScienceIdiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
1, 2Active Not RecruitingTreatmentBreast Cancer Triple Negative / Cancer of the Ovary / Cervical Cancers / Endometrial Cancers / Tumors, Solid1
1, 2CompletedTreatmentCancer, Breast2
1, 2CompletedTreatmentHealthy Males1
1, 2CompletedTreatmentRecurrent Breast Cancer / Stage IV Breast Cancer1
1, 2RecruitingTreatmentAdvanced Breast Cancer1
1, 2RecruitingTreatmentBreast Diseases / Neoplasms, Breast1
1, 2RecruitingTreatmentEndometrial Carcinoma / Hormone Receptor Positive Tumor / Metastatic Carcinoma1
1, 2TerminatedTreatmentCancer, Breast1
2Active Not RecruitingTreatmentBreast Cancer Invasive Nos1
2Active Not RecruitingTreatmentCancer, Breast4
2Active Not RecruitingTreatmentCancer, Breast / Hormone Receptor Positive Tumor / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast1
2Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2Active Not RecruitingTreatmentNeoplasms, Breast2
2CompletedPreventionHealthy Volunteers1
2CompletedTreatmentAnovulatory cycle1
2CompletedTreatmentCancer of the Ovary / Primary Peritoneal Cancer / Tubal Carcinoma1
2CompletedTreatmentCancer, Breast15
2CompletedTreatmentCancer, Breast / Early-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2CompletedTreatmentCancer, Breast / Neoplasms, Breast2
2CompletedTreatmentDCIS1
2CompletedTreatmentDepression / Diabetes Mellitus (DM) / Hypogonadism / Osteoporosis / Sarcopenia1
2CompletedTreatmentEndometriosis1
2CompletedTreatmentErectile Dysfunction (ED) / Hypogonadism / Seizures Disorders1
2CompletedTreatmentEstrogen Receptor-Positive Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGynecomastia1
2CompletedTreatmentHypogonadism1
2CompletedTreatmentMcCune-Albright Syndrome1
2CompletedTreatmentMenstruation Disorders1
2CompletedTreatmentMetastatic Breast Cancer (MBC)3
2CompletedTreatmentPuberty, Precocious1
2CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
2CompletedTreatmentTesticular Hypogonadism1
2Not Yet RecruitingOtherCancer, Breast1
2Not Yet RecruitingTreatmentBreast Diseases / Her2-Positive Breast Cancer / Hormone Receptor Positive Malignant Neoplasm of Breast / Hormone Receptor Positive Tumor / Malignant Neoplasm of Female Breast / Metastatic Breast Cancer (MBC)2
2RecruitingBasic ScienceCancer, Breast1
2RecruitingOtherCancer, Breast1
2RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Metastatic Breast Carcinoma / Metastatic Malignant Neoplasm in the Bone / Progesterone Receptor Positive / Prognostic Stage IV Breast Cancer AJCC v81
2RecruitingTreatmentBreast Cancer Invasive Nos / Cancer, Breast1
2RecruitingTreatmentBreast Cancer Metastatic1
2RecruitingTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast1
2RecruitingTreatmentCancer, Breast4
2RecruitingTreatmentCancer, Breast / Hormone Receptor Positive Tumor1
2RecruitingTreatmentCancer, Breast / Malignancies1
2RecruitingTreatmentEarly-Stage Breast Carcinoma / Estrogen Receptor Positive Tumor1
2RecruitingTreatmentEarly-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2RecruitingTreatmentEstrogen Receptor Negative / Estrogen Receptor Positive / HER2/Neu Negative / Progesterone Receptor Negative / Progesterone Receptor Positive / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma1
2RecruitingTreatmentFemale Breast Carcinoma1
2RecruitingTreatmentLow Grade Endometrial Stromal Sarcoma1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentNeoplasms, Breast2
2RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
2TerminatedTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast1
2TerminatedTreatmentCancer, Breast5
2TerminatedTreatmentCancer, Breast / Neoplasms / Neoplasms, Breast1
2TerminatedTreatmentEstrogen Receptor Positive / HER2/Neu Negative / Recurrent Breast Carcinoma / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2TerminatedTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2TerminatedTreatmentEstrogen Receptor-Positive Breast Cancer / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast / Male Breast Cancer / Recurrent Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer1
2TerminatedTreatmentEstrogen Receptor-negative Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-negative Breast Cancer / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage IIIA Breast Cancer / Triple-Negative Breast Cancer (TNBC)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Postmenopausal Women1
2TerminatedTreatmentMetastatic Breast Cancer (MBC)2
2TerminatedTreatmentNeoplasms, Breast2
2Unknown StatusTreatmentBreast Cancer Nos Premenopausal / Estrogen Receptor Positive Tumor / Metastatic Breast Cancer (MBC)1
2Unknown StatusTreatmentCancer, Breast5
2Unknown StatusTreatmentMetastatic Breast Cancer (MBC)1
2WithdrawnBasic SciencePost-menopausal ER+ Stage I-IIIA Primary Operable Breast Cancer1
2WithdrawnTreatmentBreast Cancer Metastatic1
2WithdrawnTreatmentCancer, Breast2
2WithdrawnTreatmentMetabolic Syndromes1
2, 3CompletedNot AvailableHypopituitarism1
2, 3TerminatedTreatmentCancer, Breast1
3Active Not RecruitingPreventionCancer, Breast1
3Active Not RecruitingTreatmentAdvanced Metastatic Breast Cancer / Advanced, Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBreast Adenocarcinoma / Estrogen Receptor and/or Progesterone Receptor Positive / HER2/Neu Negative / Stage IA Breast Cancer / Stage IA Breast Cancer AJCC v7 / Stage IB Breast Cancer / Stage IB Breast Cancer AJCC v7 / Stage IIA Breast Cancer / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer / Stage IIB Breast Cancer AJCC v6 and v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v71
3Active Not RecruitingTreatmentBreast Cancer Metastatic1
3Active Not RecruitingTreatmentCancer, Breast9
3Active Not RecruitingTreatmentDuctal Breast Carcinoma In Situ / Estrogen Receptor and/or Progesterone Receptor Positive / Estrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Multicentric Breast Carcinoma / Multifocal Breast Carcinoma / Progesterone Receptor Positive / Synchronous Bilateral Breast Carcinoma1
3Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Invasive Ductal Breast Carcinoma / Invasive Lobular Breast Carcinoma / Recurrent Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
3Active Not RecruitingTreatmentHormone Receptor Positive Breast Cancer1
3Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3CompletedNot AvailableBone Density1
3CompletedNot AvailableCancer, Breast1
3CompletedNot AvailableQuality of Life1
3CompletedPreventionCancer, Breast1
3CompletedTreatmentAdvanced Breast Cancer2
3CompletedTreatmentCancer, Breast15
3CompletedTreatmentGynecomastia1
3CompletedTreatmentIdiopathic Short Stature (ISS)1
3CompletedTreatmentNeoplasms, Breast2
3CompletedTreatmentProgression-free Survival1
3Not Yet RecruitingTreatmentAdvanced Breast Cancer1
3RecruitingTreatmentBreast Neoplasm Female1
3RecruitingTreatmentCancer, Breast4
3RecruitingTreatmentEstrogen Receptor Positive Breast Cancer / HER-2 Positive Breast Cancer1
3RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3SuspendedTreatmentCancer, Breast1
3TerminatedTreatmentBMI >30 kg/m2 / Oligozoospermia1
3TerminatedTreatmentCancer, Breast2
3Unknown StatusTreatmentCancer, Breast5
4CompletedHealth Services ResearchCancer, Breast1
4CompletedTreatmentCancer, Breast4
4CompletedTreatmentEndometriosis1
4CompletedTreatmentHormono-depending Adjuvant Breast Cancer1
4CompletedTreatmentStage I Breast Carcinoma1
4RecruitingTreatmentBMI >30 kg/m2 / Hypogonadism, Hypogonadotropic1
4RecruitingTreatmentEarly-Stage Breast Cancer1
4RecruitingTreatmentFemale Breast Cancer1
4RecruitingTreatmentHypogonadism / Obesity, Severe1
4RecruitingTreatmentNeoplasms, Breast1
4RecruitingTreatmentShort Stature1
4Unknown StatusTreatmentCancer, Breast1
4WithdrawnTreatmentHER2/Neu Negative / Invasive Breast Carcinoma / One to five years postmenopausal / Stage 0 Breast Cancer / Stage IA Breast Cancer1
Not AvailableActive Not RecruitingNot AvailableCancer, Breast1
Not AvailableActive Not RecruitingTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
Not AvailableActive Not RecruitingTreatmentPrader-Willi Syndrome / Silver Russell Syndrome1
Not AvailableCompletedNot AvailableAdvanced Breast Cancer1
Not AvailableCompletedNot AvailableArthralgia/joint pain / BMI >30 kg/m2 / Cancer, Breast1
Not AvailableCompletedNot AvailableCancer, Breast5
Not AvailableCompletedNot AvailableArthralgia/joint pain / Cancer, Breast / Pain NOS1
Not AvailableCompletedNot AvailableArthralgia/joint pain / Post Menopausal1
Not AvailableCompletedNot AvailableArthralgia/joint pain1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Menopausal Syndromes1
Not AvailableCompletedBasic ScienceCancer, Breast2
Not AvailableCompletedTreatmentBreast Cancer Invasive Nos1
Not AvailableCompletedTreatmentCancer, Breast3
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
Not AvailableEnrolling by InvitationNot AvailableCancer, Breast1
Not AvailableRecruitingNot AvailableHR+ HER2- Men, Pre/Postmenopausal Advanced Breast Cancer / HR+ HER2- Postmenopausal Advanced Breast Cancer1
Not AvailableRecruitingOtherHypogonadism1
Not AvailableRecruitingSupportive CareEstrogen Receptor-Positive Breast Cancer / Musculoskeletal Complications / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
Not AvailableRecruitingTreatmentCancer, Breast2
Not AvailableSuspendedTreatmentMetabolic Syndromes1
Not AvailableTerminatedNot AvailableCancer, Breast1
Not AvailableUnknown StatusNot AvailableArthralgia/joint pain / Arthritis / Neoplasms, Breast / Polymorphism, Genetic1
Not AvailableUnknown StatusTreatmentMetabolic Syndromes1
Not AvailableWithdrawnOtherHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Accord Healthcare
  • Ascend Laboratories LLC
  • AstraZeneca Inc.
  • Breckenridge Pharmaceuticals
  • Cadila Healthcare Ltd.
  • Cypress Pharmaceutical Inc.
  • Doctor Reddys Laboratories Ltd.
  • Kaiser Foundation Hospital
  • Karalex Pharmaceuticals
  • Lake Erie Medical and Surgical Supply
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sandoz
  • Teva Pharmaceutical Industries Ltd.
  • Three Rivers Pharmaceuticals LLC
  • UDL Laboratories
  • Zeneca Pharma Inc.
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral1 mg/1
Tablet, coatedOral1 mg/1
Tablet, film coatedOral1 mg/1
TabletOral
PelletOral
Prices
Unit descriptionCostUnit
Anastrozole 100% powder1326.52USD g
Arimidex 1 mg tablet15.3USD tablet
Aromasin 25 mg tablet14.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE36617No2000-03-142010-06-27Us
CA1337420No1995-10-242012-10-24Canada
Additional Data Available
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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.53 mg/mLCanadian label (DPD)
logP1.58Canadian label (DPD)
pKa1.4Canadian label (DPD)
Predicted Properties
PropertyValueSource
Water Solubility0.0661 mg/mLALOGPS
logP2.31ALOGPS
logP3.03ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area78.29 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.47 m3·mol-1ChemAxon
Polarizability31.97 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9965
Blood Brain Barrier+0.9382
Caco-2 permeable+0.5516
P-glycoprotein substrateNon-substrate0.6405
P-glycoprotein inhibitor INon-inhibitor0.764
P-glycoprotein inhibitor IINon-inhibitor0.7662
Renal organic cation transporterNon-inhibitor0.512
CYP450 2C9 substrateNon-substrate0.803
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5761
CYP450 1A2 substrateNon-inhibitor0.6218
CYP450 2C9 inhibitorNon-inhibitor0.7616
CYP450 2D6 inhibitorNon-inhibitor0.9183
CYP450 2C19 inhibitorNon-inhibitor0.6404
CYP450 3A4 inhibitorNon-inhibitor0.6501
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7038
Ames testNon AMES toxic0.6394
CarcinogenicityNon-carcinogens0.8068
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5564 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9464
hERG inhibition (predictor II)Non-inhibitor0.8878
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004l-1390000000-8636c0aef7d79b805328
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004l-0190000000-739ac0c546bb150b1c60
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0090000000-8ccdc5fa9f18334eae92

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Triazoles / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenylpropane / Heteroaromatic compound / 1,2,4-triazole / Azole / Azacycle / Organoheterocyclic compound / Nitrile / Carbonitrile / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, triazoles (CHEBI:2704)

Targets

Details
1. Cytochrome P450 19A1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM: An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Cancer. 2002 Nov 1;95(9):2006-16. doi: 10.1002/cncr.10908. [PubMed:12404296]
  2. Miller WR: Aromatase inhibitors: mechanism of action and role in the treatment of breast cancer. Semin Oncol. 2003 Aug;30(4 Suppl 14):3-11. [PubMed:14513432]
  3. Kelly CM, Buzdar AU: Anastrozole. Expert Opin Drug Saf. 2010 Nov;9(6):995-1003. doi: 10.1517/14740338.2010.515977. [PubMed:20923259]
  4. FDA Approved Drugs: Anastrozole [Link]
  5. DPD Approved Drugs: Anastrozole [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
  2. Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [PubMed:9152599]
  3. FDA Approved Drugs: Anastrozole [Link]
  4. DPD Approved Drugs: Anastrozole [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
  2. FDA Approved Drugs: Anastrozole [Link]
  3. DPD Approved Drugs: Anastrozole [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x. [PubMed:21175441]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [PubMed:9152599]
  2. FDA Approved Drugs: Anastrozole [Link]
  3. DPD Approved Drugs: Anastrozole [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [PubMed:9152599]
  2. FDA Approved Drugs: Anastrozole [Link]
  3. DPD Approved Drugs: Anastrozole [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Miyajima M, Kusuhara H, Takahashi K, Takashima T, Hosoya T, Watanabe Y, Sugiyama Y: Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system. J Pharm Sci. 2013 Sep;102(9):3309-19. doi: 10.1002/jps.23600. Epub 2013 May 27. [PubMed:23712697]
  2. Gervasini G, Jara C, Olier C, Romero N, Martinez R, Carrillo JA: Polymorphisms in ABCB1 and CYP19A1 genes affect anastrozole plasma concentrations and clinical outcomes in postmenopausal breast cancer patients. Br J Clin Pharmacol. 2017 Mar;83(3):562-571. doi: 10.1111/bcp.13130. Epub 2016 Oct 18. [PubMed:27747906]

Drug created on June 13, 2005 07:24 / Updated on October 22, 2019 18:27