Drug reference

Fulvestrant

SERM · Antineoplastic

SERMAntineoplasticATC null

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

Manufacturer advises avoid—increased incidence of fetal abnormalities and death in animal studies.

FDA category + note

Mechanism

Fulvestrant is a pure estrogen receptor antagonist and selective estrogen receptor degrader (SERD) that binds to the estrogen receptor with affinity comparable to estradiol but induces a conformational change that accelerates receptor degradation via the proteasome. Unlike tamoxifen, it has no partial agonist activity in any tissue, producing complete estrogen receptor blockade and downregulation. This makes it effective in tamoxifen-resistant breast cancers where partial agonism may drive tumor growth.

Indications

Oestrogen-receptor-positive breast cancerHormone receptor-positive, HER2-negative, advanced breast cancerLocally advanced or metastatic oestrogen-receptor positive breast cancertreatment of breast cancer (in women with disease progression after tamoxifen)treatment of breast cancer (in women with resistance to aromatase inhibitors)breast cancer (ER expression)Advanced or metastatic HR+ breast cancer (+/- CDK4/6 inhibitors or +/– PI3K inhibitor alpelisib) in postmenopausal women who have disease progression after antiestrogen therapyER+/PR+ metastatic breast cancer in premenopausal women receiving GnRH agonists as antiestrogen therapyMetastatic ER positive breast cancer in postmenopausal women (when unresponsive to tamoxifen)Carcinoma breast (adjuvant and palliative therapy)Breast cancer (primary and secondary prevention)For ER-positive metastatic breast cancer patients without ESR1 mutation who have received an aromatase inhibitorMay be coupled with a CDK4/6 inhibitor if the patient has not previously received such an agentIn combination with alpelisib for postmenopausal patients with PIKC3A mutationIn combination with capivasertib for patients with PIK3CA/AKT1/PTEN alterations

Dosing

Adult: 500 mg by deep intramuscular injection into the buttock, every 2 weeks for the first 3 doses, then 500 mg every month. The 500 mg dose should be administered as two 250 mg injections (slowly over 1-2 minutes) into each buttock.

Pharmacokinetics

Onset

Steady-state levels are achieved within the first month with the specified dosing regimen. Cmax is reached approximately 7 days after intramuscular administration.

Half-life

Plasma half-life is approximately 40 days.

Protein binding

Rapid distribution and extensive protein binding due to its highly lipophilic nature.

Metabolism

numerous metabolites formed in vivo, possibly by pathways similar to endogenous estrogen metabolism

Excretion

primarily (90%) via the feces

Side effects

Common

Appetite decreasedArthralgiaAstheniaDiarrhoeaHeadacheHot flushHypersensitivityIncreased risk of infectionNauseaPainRashVaginal haemorrhageVenous thromboembolismVomitinghot flashesgastrointestinal symptomsback painpharyngitisAsthenia (weakness)Arthralgias (joint pain)Injection site reactions (seen in almost 10% of patients)

Serious