Drug/Small Molecule:
fulvestrant

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 fulvestrant and ESR1, ESR2

This label is on the FDA Biomarker List
Genetic testing required

Summary

Fulvestrant is used to treat hormone-receptor positive breast cancer in postmenopausal women whose disease has spread after treatment with an antiestrogen medicine.

Annotation

Excerpts from the Fulvestrant (Faslodex) drug label:

Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells.

Dose adjustment is not needed in patients co-prescribed CYP3A4 inhibitors or inducers.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Fulvestrant 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

  • CYP3A4
    • Drug interactions section, Clinical pharmacology section, metabolism/PK
    • source: FDA Label
  • ESR1
    • Indications & usage section, Description section, Clinical pharmacology section, efficacy
    • source: FDA Label

last updated 10/25/2013

European Medicines Agency (EMA) Label for fulvestrant and ESR1, ESR2, MKI67

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) contains biomarker information regarding the indication of Fulvestrant (Faslodex) in postmenopausal women with estrogen receptor positive breast cancer due to its mechanism of action.

Annotation

Excerpt from the Fulvestrant (Faslodex) EPAR:

Faslodex is indicated for the treatment of postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on therapy with an anti-estrogen.


Fulvestrant is a competitive estrogen receptor (ER) antagonist with an affinity comparable to estradiol. Fulvestrant blocks the trophic actions of estrogens without any partial agonist (estrogen-like) activity. The mechanism of action is associated with down-regulation of estrogen receptor protein levels. Clinical trials in postmenopausal women with primary breast cancer have shown that fulvestrant significantly down-regulates ER protein in ER positive tumours compared with placebo. There was also a significant decrease in progesterone receptor expression consistent with a lack of intrinsic estrogen agonist effects. It has also been shown that fulvestrant 500 mg downregulates ER and the proliferation marker Ki67, to a greater degree than fulvestrant 250 mg in breast tumours in postmenopausal neoadjuvant setting.

This information is highlighted in the following sections:
Therapeutic indications, pharmacodynamic properties, information for the user.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the fulvestrant EMA drug label.

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


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.

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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?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • ICI 182,780
  • fulvestrant
Trade Names
  • Faslodex
Brand Mixture Names

PharmGKB Accession Id:
PA164747170

Description

Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor.

Source: Drug Bank

Indication

For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines.

Source: Drug Bank

Pharmacology

Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Metabolism of fulvestrant appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3 and 17 positions of the steroid nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models. Studies using human liver preparations and recombinant human enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown.

Source: Drug Bank

Protein Binding

99% (mainly VLDL, LDL, and HDL)

Source: Drug Bank

Half-Life

40 days

Source: Drug Bank

Toxicity

There is no clinical experience with overdosage in humans.

Source: Drug Bank

Route of Elimination

Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%).
Renal elimination was negligible (less than 1%).

Source: Drug Bank

Volume of Distribution

  • 3 to 5 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C32H47F5O3S

Source: Drug Bank

Isomeric SMILES

C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)[C@@H](CC4=C3C=CC(=C4)O)CCCCCCCCC[S@@](=O)CCCC(C(F)(F)F)(F)F

Source: Drug Bank

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H])C=C(O)C=C3

Source: Drug Bank

Canonical SMILES

[H][C@@]

Source: Drug Bank

Average Molecular Weight

606.771

Source: Drug Bank

Monoisotopic Molecular Weight

606.316607085

Source: Drug Bank

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 ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ESR1
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ESR2
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
MKI67

Drug Targets

Gene Description
ESR1 (source: Drug Bank)
No related drugs are available.

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

May Treat
Contraindicated With

Publications related to fulvestrant: 3

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 No Variant Annotation available No VIP available No VIP available
Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer. Oncogene. 2010. Lin Z, 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
An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2 expression. Oncogene. 1997. Bates N P, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0310-0720-50
DrugBank:
DB00947
ChEBI:
31638
KEGG Drug:
D01161
PubChem Compound:
104741
IUPHAR Ligand:
1015
Drugs Product Database (DPD):
2248624
BindingDB:
50169743
Therapeutic Targets Database:
DAP000319
FDA Drug Label at DailyMed:
83d7a440-e904-4e36-afb5-cb02b1c919f7

Clinical Trials

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

Common Searches

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