Drug/Small Molecule:
exemestane

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for exemestane and ESR1, ESR2

This label is on the FDA Biomarker List
Informative PGx

Summary

Aromasin is an aromatase inhibitor indicated for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen.

Annotation

Excerpts from the exemestane (Aromasin) label:

Aromasin is an aromatase inhibitor indicated for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to Aromasin for completion of a total of five consecutive years of adjuvant hormonal therapy.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the exemestane (Aromasin) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Breast Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • CYP3A4
    • Dosage & administration section, Drug interactions section, dosage, efficacy
    • source: FDA Label

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs11849538 *916+326G>C, *921+326G>C, 1620+326G>C, 77175978C>G, 96175978C>G
C > G
Intronic
No VIP available CA VA
rs16964189 22284794C>T, 51494237C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs2369049 77171851A>G, 96171851A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs6493497 -182C>T, -291C>T, 22421392G>A, 4961C>T, 51630835G>A
G > A
5' Flanking
No VIP available CA VA
rs7176005 -626G>A, -735G>A, 22421836C>T, 4517G>A, 51631279C>T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs9322336 152200430C>T, 193800C>T, 56369887C>T, 644-1360C>T
C > T
Intronic
No VIP available CA VA
rs934635 22269334G>A, 51478777G>A
G > A
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Exemestano [INN-Spanish]
  • Exemestanum [INN-Latin]
  • exemestane
Trade Names
  • Aromasin
  • Exemestance
Brand Mixture Names

PharmGKB Accession Id:
PA449563

Description

Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation.

Source: Drug Bank

Indication

For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition". Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on the adrenal biosynthesis of corticosteroids or aldosterone. This reduction in serum and tumor concentrations of estrogen delays tumor growth and disease progression. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.

Source: Drug Bank

Pharmacology

Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex tm ), letrozole (Femara tm ) and exemestane (Aromasin tm ).

Source: Drug Bank

Food Interaction

High-fat meals increase plasma exemestane concentrations by approximately 40%.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

90% (mainly alpha1-acid glycoprotein and albumin)

Source: Drug Bank

Absorption

42%

Source: Drug Bank

Half-Life

24 hours

Source: Drug Bank

Toxicity

Convulsions

Source: Drug Bank

Chemical Properties

Chemical Formula

C20H24O2

Source: Drug Bank

Isomeric SMILES

C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CC(=C)C4=CC(=O)C=C[C@]34C

Source: Drug Bank

[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC(=C)C2=CC(=O)C=C[C@]12C

Source: Drug Bank

Canonical SMILES

C[C@]12CC[C@H]

Source: Drug Bank

Average Molecular Weight

296.4034

Source: Drug Bank

Monoisotopic Molecular Weight

296.177630012

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics
    Summary of pathways of estrogens and antiestrogens.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
CYP19A1 (source: Drug Bank)
No related drugs are available.

Curated Information ?

EvidenceDisease
No Dosing Guideline available DL CA VA No VIP available No VIP available
Breast Neoplasms

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to exemestane: 14

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial. Breast cancer research and treatment. 2014. Fontein Duveken B Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects. British journal of cancer. 2013. Henry N L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer. Breast cancer research and treatment. 2013. Henry N Lynn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Mammographic breast density response to aromatase inhibition. Clinical cancer research : an official journal of the American Association for Cancer Research. 2013. Vachon Celine M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012. Henry N Lynn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Comparison of Changes in the Lipid Profile of Postmenopausal Women With Early Stage Breast Cancer Treated With Exemestane or Letrozole. Journal of clinical pharmacology. 2011. Bell Lauren Nicole, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. Journal of medicinal chemistry. 2011. Kido Yasuto, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. Ingle James N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of 17-dihydroexemestane glucuronidation: potential role of the UGT2B17 deletion in exemestane pharmacogenetics. Pharmacogenetics and genomics. 2010. Sun Dongxiao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
In Vitro P450-Mediated Metabolism of Exemestane. Drug metabolism and disposition: the biological fate of chemicals. 2010. Kamdem Landry K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case-control study. British journal of cancer. 2010. Henry N L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjuvant therapy with aromatase inhibitors. Cancer research. 2010. Wang Liewei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antiestrogen pathway (aromatase inhibitor). Pharmacogenetics and genomics. 2009. Desta Zeruesenay, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0009-7663-04
DrugBank:
DB00990
ChEBI:
4953
KEGG Compound:
C08162
KEGG Drug:
D00963
PubChem Compound:
60198
PubChem Substance:
196561
46508243
Drugs Product Database (DPD):
2242705
ChemSpider:
54278
Therapeutic Targets Database:
DAP000625
FDA Drug Label at DailyMed:
cf066b7a-032a-416c-8d40-15ba581423e3

Clinical Trials

These are trials that mention exemestane and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.