Treatment of breast cancer with current estrogen receptors, locally advanced or metastatic, in postmenopausal women, when the disease has come back during or after the completion of adjuvant therapy with the antiestrogen or if the disease progressed during the treatment with the antiestrogen drug.
Fulvestrant is a competitive estrogen receptor antagonist with an affinity comparable to estradiol. It blocks the trophic effects of estrogens without showing even a partial (estrogen-like) agonist effect. The mechanism of action is to reduce the amount of estrogen receptor receptor protein. In postmenopausal women with primary breast cancer, fulvestrant significantly reduced the amount of estrogen receptor protein in tumors containing estrogen receptors compared to placebo. There are no data on the long-term effects of fulvestrant on the post-menopausal uterine mucosa. There are no data on the long-term effects of fulvestrant on bone. After administration of the drug in the form of an intramuscular injection with long-term action, fulvestrant is slowly absorbed and reaches its maximum concentration in the blood after about 5 days. Fulvestrant binds 99% of plasma proteins. Fulvestrant is primarily associated with lipoprotein fractions with very small (VLDL), low (LDL) and high density (HDL) fractions. Fulvestrant metabolism has not been fully understood and is taking place through many biological changes in a similar way to endogenous steroids. Detected drug metabolites are less than fulvestrant or comparable antiestrogenic activity. CYP3A4 is the only cytochrome P450 isoenzyme involved in fulvestrant oxidation. The drug is excreted mainly in metabolised form, mainly with faeces, less than 1% is excreted in the urine. T0,5 depends primarily on the rate of absorption and is about 50 days.
Contraindications:
Hypersensitivity to the active substance or any of the excipients. Pregnancy and breastfeeding. Severe liver dysfunction.
Precautions:
It should be used with caution in patients with mild to moderate hepatic impairment, severe renal impairment (creatinine clearance below 30 ml / min), haemorrhagic diathesis, thrombocytopenia or in patients taking anticoagulants. Patients with advanced breast cancer often have thromboembolic disorders; this should be taken into account when using the preparation in patients at risk. There are no data on the long-term effects of fulvestrant on bones - there is a potential risk of osteoporosis due to the fulvestrant mechanism.
Pregnancy and lactation:
The preparation is contraindicated in pregnancy and breast-feeding. Patients of childbearing age should use effective methods of contraception.
Side effects:
Very common: nausea, increased liver enzymes (ALAT, AST, alkaline phosphatase), asthenia, reactions at the site of administration. Common: urinary tract infections, hypersensitivity reactions, anorexia, headache, venous thromboembolism, hot flushes, vomiting, diarrhea, increased bilirubin, rash, backache. Uncommon: liver failure, hepatitis, increased GGT activity, vaginal candidiasis, profuse whitish discharge, vaginal bleeding, bleeding from the injection site, hematoma at the injection site.
Dosage:
Intramuscularly. Adult patients (also elderly): the recommended dose is 500 mg administered one month apart with an additional 500 mg dose two weeks after the first dose.Special groups of patients. No dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance ≥30 ml / min). The efficacy and safety of the product have not been studied in patients with severe renal impairment (creatinine clearance <30 ml / min), therefore caution is recommended when used in this group of patients.No dose adjustment is required in patients with mild or moderate hepatic impairment. However, in this group of patients, the drug should be used with caution due to the possibility of increasing the exposure to fulvestrant. There are no data on use in patients with severe hepatic impairment. It is not recommended for use in children and adolescents up to 18 years of age, due to the lack of data on safety and efficacy in this age group.Method of administration. The drug should be administered slowly (time of one injection of 1-2 minutes), intramuscularly in 2 consecutive injections of 5 ml, each in a different buttock.
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