Chemical: Drug
fulvestrant

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


Annotated Labels

  1. FDA Label for fulvestrant and ESR1,PGR
  2. EMA Label for fulvestrant and ESR1,ESR2,MKI67
  3. PMDA Label for fulvestrant and ESR1,ESR2


last updated 10/25/2013

2. 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.

There's more of this label. Read more.


last updated 01/26/2015

3. PMDA Label for fulvestrant and ESR1,ESR2

Genetic testing required

Summary

The PMDA package insert for fulvestrant states that it is indicated for postmenopausal women with hormone-receptor positive breast cancer, and that fulvestrant should not be used in women negative for hormone receptor.

There's more of this label. Read more.


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

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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Overview

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

PharmGKB Accession Id

PA164747170

Type(s):

Drug

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

SMILES

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])C2[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=CC(O)=CC=C12

Source: Drug Bank

InChI String

InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29?,30+,41?/m1/s1

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 ?

Drug Targets

Gene Description
ESR1 (source: Drug Bank)

Curated Information ?

EvidenceDrug
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
anastrozole

Curated Information ?

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

May Treat
Contraindicated With

Publications related to fulvestrant: 7

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. British journal of clinical pharmacology. 2016. Hertz Daniel 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
Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nature genetics. 2013. Robinson Dan R, 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
ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nature genetics. 2013. Toy Weiyi, 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 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
Family 1 uridine-5'-diphosphate glucuronosyltransferases (UGT1A): from Gilbert's syndrome to genetic organization and variability. Archives of toxicology. 2008. Strassburg Christian P, 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.

No trials found.

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Sources for PharmGKB drug information: DrugBank, PubChem.