Fulvestrant

What it is and how it works

Mechanism of Action 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. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines. In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice.

Mechanism class: Estrogen Receptor Antagonists · Selective Estrogen Receptor Modulators

Indications

Monotherapy Fulvestrant injection is indicated for the treatment of: • Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or • HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy Fulvestrant injection is indicated for the treatment of: • HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. • HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. Fulvestrant is an estrogen receptor antagonist indicated for the treatment of: • Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy.

Dosage and administration (summary)

• Fulvestrant injection 500 mg should be administered intramuscularly into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as two 5 mL injections, one in each buttock, on Days 1, 15, 29 and once monthly thereafter. ( 2.1 , 14 ) • A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock (gluteal area) slowly (1 to 2 minutes) as one 5 mL injection on Days 1, 15, 29 and once monthly thereafter.

Contraindications

Fulvestrant is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant . • Hypersensitivity.

Warnings and precautions

• Risk of Bleeding: Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. • Increased Exposure in Patients with Hepatic Impairment: Use a 250 mg dose for patients with moderate hepatic impairment. ( 2.2 , 5.2 , 8.6 ) • Injection Site Reaction: Use caution while administering fulvestrant at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman . There are no available data in pregnant women to inform the drug-associated risk.

Storage and supply

Fulvestrant injection is supplied as two 5 mL clear neutral glass (Type 1) barrels, each containing 250 mg/5 mL of fulvestrant solution for intramuscular injection. NDC 0781–3532–12 Carton containing 2 single-dose pre-filled syringes The single-dose prefilled syringes are presented in a tray with polystyrene plunger rod and safety needles (SafetyGl…

Source: Fulvestrant (Fulvestrant) — US FDA prescribing information, 2022-09-13, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.