Fazlodex solution for injections syringe 250 mg/5 ml. 5 ml №2

Description

Fazlodex Storage
active substance: 1 pre-filled syringe (5 ml) contains 250 mg of fulvestrant;

excipients: ethanol 96%, benzyl alcohol, benzyl benzoate, castor oil.

Fazlodex Dosage form
Solution for injection.

Main physical and chemical properties: clear, colorless to yellow, viscous liquid.

Fazlodex Pharmacotherapeutic group
Hormone antagonists and similar drugs. Antiestrogens. ATX code L02B A03.

Pharmacological properties

Pharmacodynamics.

Mechanism of action and pharmacodynamic effects

Fulvestrant is a competitive estrogen receptor (EP) antagonist, the affinity of which is comparable to estradiol. Fulvestrant blocks the trophic action of estrogen without exhibiting partial agonistic (estrogen-like) activity. The mechanism of action is associated with the negative regulation of estrogen receptor protein levels.

Clinical studies in postmenopausal women with primary breast cancer have shown that fulvestrant significantly reduces EP protein levels in tumors with positive ERs compared to placebo. There was also a significant decrease in the expression of progesterone receptors, which is consistent with the lack of estrogen agonist-specific effects. Fulvestrant 500 mg has also been shown to inhibit EP and the marker of Ki67 proliferation in breast tumors to a greater extent than fulvestrant at a dose of 250 mg in neoadjuvant treatment of postmenopausal women.

Clinical safety and efficacy of the drug in late stages of breast cancer

Monotherapy

A phase 3 clinical trial was conducted in 736 postmenopausal women with advanced breast cancer who had a recurrence of the disease on or after adjuvant endocrine therapy or progression after endocrine therapy for a common disease. The study included 423 patients in whom the disease recurred or progressed during antiestrogen therapy (subgroup AE) and 313 patients in whom the disease recurred or progressed during treatment with aromatase inhibitors (subgroup AI). This study compared the efficacy and safety of Fazlodex at a dose of 500 mg (n = 362) and at a dose of 250 mg (n = 374). The main endpoint was progression-free survival (WFD); Key secondary efficacy endpoints included objective response rate (OBR), clinical efficacy frequency (CLE), and overall survival (SV).

Indication
Fazlodex is shown:

as monotherapy for the treatment of locally advanced or metastatic breast cancer with estrogen-positive receptors in postmenopausal women:
who have not previously received endocrine therapy, or
in case of recurrence of the disease during or after adjuvant antiestrogen therapy or disease progression during antiestrogen therapy;
in combination with palbocyclib for the treatment of hormone-receptor-positive (HR-positive), negative epidermal growth factor receptor 2 (HER2) local or metastatic breast cancer in women receiving prior endocrine therapy (see Pharmacodynamics) .
In premenopausal or perimenopausal women, combination therapy with palbocyclib should be given in combination with a luteinizing hormone-releasing hormone (LHRH) agonist.

Contraindication
Hypersensitivity to the active substance or to any of the excipients.

Pregnancy and lactation (see section “Use during pregnancy or breastfeeding”).

Severe hepatic insufficiency (see sections “Features of use” and “Pharmacokinetics”).