Tamoxifen is a non-steroidal triphenylethylene derivative. Depending on the tissue, it acts as an estrogen antagonist or agonist. In breast cancer patients, Tamoxifen acts primarily as an antiestrogen. By binding to the estrogen receptor in the tumor, it prevents the binding of estrogens to this receptor. In clinical trials, in some patients, despite the absence of an estrogen receptor in the tumor, tamoxifen also has a beneficial clinical effect. In these cases, the mechanism of action of tamoxifen is probably different. In post-menopausal women, the preparation reduces the total cholesterol and low-density lipoprotein (LDL) levels by 10-20%. It does not reduce bone mineral density. After oral administration, the drug is quickly absorbed from the gastrointestinal tract, reaching a maximum concentration in the blood after 4-7 h. Steady state is reached after approximately 4 weeks of treatment at a dose of 40 mg per day. It is strongly bound to plasma proteins. Tamoxifen is metabolized by hydroxylation, demethylation and conjugation. Some of the metabolites have a clinical effect similar to tamoxifen. Tamoxifen is mainly excreted in the faeces. His T0,5 is about 7 days, and for the main metabolite - N-demethylamamoxifen - 14 days.
Contraindications:
Hypersensitivity to tamoxifen or any of the ingredients. Pregnancy (in pre-menopausal women, pregnancy should be excluded before starting treatment with tamoxifen).
Precautions:
During treatment with Tamoxifen, an increase in the incidence of changes in the endometrium such as hypertrophy, polyps and cancer was observed. Special caution should be exercised in patients who have been previously treated with tamoxifen and have had adverse effects on the reproductive system during treatment, especially genital tract bleeding, menstrual disorders, vaginal discharge, pain and / or a heaviness in the abdomen. Diagnostic procedures should be initiated if similar symptoms occur during re-treatment with tamoxifen. Caution should be exercised in patients at risk of venous thromboembolism; in addition, the risk increases with age, in the case of significant obesity and if there are other risk factors for this syndrome - the risk and benefits of tamoxifen treatment before its use should be considered in all patients. In patients with breast cancer treated with tamoxifen, the risk of having thromboembolic syndrome is also greater when chemotherapy is given concomitantly. If the patient develops symptoms of thromboembolism, treatment with tamoxifen should be stopped immediately and appropriate anticoagulant therapy initiated. This medicine is not recommended in children because safety and efficacy have not been established in this age group. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
Do not use the drug in pregnant women. In women of childbearing potential, effective non-hormonal contraception should be used. In pre-menopausal women, pregnancy should be ruled out before starting treatment. Avoid using the drug in breastfeeding women.
Side effects:
They result either from the pharmacological action of the drug, e.g. hot flush, genital tract bleeding, discharge, vulval itching, transient worsening of cancer symptoms, or general action, e.g. gastrointestinal disorders, headache, dissociation and in very rare cases detention fluid in the body and baldness. Leg muscle cramps were common. In very rare cases, skin lesions have been observed, including isolated cases of erythema multiforme, Stevens-Johnson syndrome, and pemphigus. In rare cases, hypersensitivity reactions have occurred, also in the form of angioedema. In a small number of patients who had metastases to the bone, hypercalcemia occurred at the beginning of treatment.Leukopenia (sometimes accompanied by anemia and / or thrombocytopenia), neutropenia, visual disturbances (including changes in the cornea, retinopathy, cataract) were also observed. There have been cases of uterine fibroids, endometriosis and other changes in the endometrium (ie hyperplasia and polyps), enlargement of ovarian cysts, increased incidence of endometrial cancer and uterine sarcomas (mainly malignant mesodermal mixed tumors). Changes in liver enzymes have been observed, in rare cases other serious abnormalities of liver function (eg fatty liver, cholestasis and hepatitis), as well as increased triglycerides in the blood, sometimes occurring concurrently with pancreatitis. Deep vein thrombosis and pulmonary embolism were observed during treatment with tamoxifen; in very rare cases, the occurrence of interstitial pneumonia has been observed.
Dosage:
Orally. Adults: the recommended daily dose is 20 mg. There were no additional benefits when using the product at higher doses, such as delayed relapse or improved survival. There are no relevant clinical data to support tamoxifen 30-40 mg per day, although some patients with advanced disease received tamoxifen at these doses. Elderly patients do not need to change their dosage.
(C)
