| Indication |
For the treatment of hormone receptor positive metastatic breast
cancer in postmenopausal women with disease progression following
anti-estrogen therapy. |
| Pharmacodynamics |
Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects. |
| 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. |
| Absorption |
Not Available |
| Volume of distribution |
|
| Protein binding |
99% (mainly VLDL, LDL, and HDL) |
| Metabolism |
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. |
| 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%). |
| Half life |
40 days |
| Clearance |
Not Available |
| Toxicity |
There is no clinical experience with overdosage in humans. |
