elacestrant

Action and Spectrum

Actions and Spectrum:

elacestrant (also known as FDX104) is a selective estrogen receptor downregulator (SERD) medication used for the treatment of breast cancer in postmenopausal women.

The mechanism of action of elacestrant is to selectively bind to and inhibit the activity of estrogen receptors (ER) in breast cancer cells. By blocking ER, elacestrant can help to reduce the growth and spread of ER-positive breast cancer cells.

Elacestrant has been shown to have a wide spectrum of activity in preclinical studies, with efficacy in models of ER-positive and HER2-negative breast cancer, as well as in models of breast cancer resistance protein (BCRP)-positive tumors.

Drug Interaction

Adverse Reaction

Frequency Defined 

>10%  

Nausea (35%)

Musculoskeletal pain (41%)

Cholesterol increased (30%)

Triglycerides increased (27%)

AST increased (29%)

Fatigue (26%)

Vomiting (19%)

Hemoglobin decreased (26%)

ALT increased (17%)

Creatinine increased (16%)

Sodium decreased (16%)

Decreased appetite (15%)

Constipation (12%)

Diarrhea (13%)

Headache (12%)

Hot flush (11%)

Abdominal pain (11%)

1-10%

All grades

Nausea (2.5%)

Musculoskeletal pain (7%)

Fatigue (2%)

Triglycerides increased (2%)

Headache (2%)

Black Box Warning

Black Box Warning

LIMITED information

Contraindication / Caution

Contraindication/Caution:

Limited information

Pregnancy / Lactation

Pregnancy warnings:   

US FDA pregnancy category: N/A

Lactation:  

Excreted into human milk is UNknown

Pregnancy Categories:        

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

Elacestrant (also known as MK-6482) is a selective estrogen receptor degrader (SERD) that is being developed as a treatment for estrogen receptor positive (ER+) breast cancer.

Pharmacodynamics: 

It works by binding to the estrogen receptor and causing its degradation, thus reducing the amount of estrogen signaling in cancer cells. The result is an inhibition of cell growth and proliferation, leading to a potential reduction in tumor size.

Pharmacokinetics: 

Absorption

When compared to administration, taking 345 mg with a high-fat meal (800–1000 calories, 50% fat) increased Cmax by 42% and AUC by 22%

Distribution 

99% of proteins are bound and Volume of distribution: 5800 L

Metabolism 

CYP3A4 is the main metabolising enzyme, with CYP2A6 and CYP2C9 having minor roles.

Elimination and excretion 

30- to 50-hour half-life

Clearance: 186 L/hr and kidney clearance: 0.14 L per hour Urine 7.5% (1% unaltered), faeces 82% (34% unchanged)

Adminstartion

Administration: 

Oral administration

elacestrant is a medication used in the treatment of breast cancer. It is administered as a once-daily oral tablet.

The recommended dosage of elacestrant is 75 mg once daily, with or without food. The treatment should be continued until the patient experiences disease progression or develops unacceptable toxicity.

Patient Information Leaflet

Patient information leaflet

Generic Name: elacestrant

Why do we use elacestrant?

elacestrant is used for the treatment of advanced or metastatic breast cancer in postmenopausal women. It is a selective estrogen receptor degrader (SERD) that works by binding to the estrogen receptor and blocking the effects of estrogen in the body.

Breast cancer often grows in response to the hormone estrogen. elacestrant is used to treat breast cancers that are hormone receptor-positive, meaning they need estrogen to grow.