Antineoplastic anti-estrogenic non-steroidal agent.
The mechanism of antitumor effect is due to competitive binding to estrogen receptors in target organs and inhibition of the formation of the estrogen Tamoxifen complex with the endogenous ligand 17-r-estradiol.
The pharmacological action of tamoxifen is realized not by the compound itself, but by its active metabolite called endoxifene and formed during metabolic biotransformation with the participation of the isoenzyme of the cytochrome CYP2D6 system, therefore polymorphism by the activity of the CYP2D6 isoenzyme may be associated with differences in the clinical effect achieved. Slow metabolizers may experience a decrease in the therapeutic effect. The full effect of the treatment with ta-moxifen in slow metabolizers for CYP2D6 has not been studied.
CYP2D6 genotype: the available clinical data suggest that in patients who are homozygous for a recessive allele, there may be a decrease in the therapeutic efficacy of tamoxifen in the treatment of breast cancer. These clinical trials have mostly been conducted in postmenopausal women
After ingestion, it is well absorbed from the gastrointestinal tract. The maximum concentration in the blood is reached within 4-7 hours after administration. A stable therapeutic concentration in the blood (about 300 ng / l) is established after 4 weeks of treatment at a dose of 0.04 g / day. The association with serum albumins is almost 99%. Metabolised in the liver by hydroxylation, demethylation and subsequent conjugation, resulting in a number of metabolites that have the same pharmacological profile with the parent substance. The bulk of tamoxifen is initially metabolized with the participation of the CYP3A4 isoenzyme to N-desmethyltamoxifen and then with the participation of CYP2D6 to another active metabolite, endoxyphene. In patients with a decreased activity of the CYP2D6 isoenzyme, the endoxifene concentration is approximately 75% lower than in patients with normal CYP2D6 activity. Simultaneous administration of strong inhibitors of CYP2D6 approximately equally reduces the plasma concentration of endoxifene.
Tamoxifen is excreted mainly with bile. Only a small amount of the drug is excreted in the urine. The half-life of the initial preparation is approximately 7 days, for the active metabolite -14 days.
Indications for use
Breast cancer in women.
The drug is used for adjuvant therapy of breast cancer in women with affected lymph nodes, as well as metastatic breast cancer in men and women.
Increased individual sensitivity to tamoxifen, severe leukopenia, thrombocytopenia, hypercalcemia, pregnancy, lactation
Dosing and Administration
Tablets are given inside without chewing, with a small amount of water. If two or more tablets are prescribed per day, they can be taken in one or two doses.
The recommended daily dose of tamoxifen for adults is 20 mg. In the case of widespread forms of the disease, the doses may be increased to 30-40 mg per day. The maximum daily dose of tamoxifen is 40 mg. Objectively, the effect of therapy is usually observed after 4-10 weeks of treatment, but in the case of metastases in the bones, the effect can be observed only after several months of treatment.
The duration of treatment with tamoxifen is determined by the severity and course of the disease. Usually treatment is lengthy. “
In the treatment of elderly patients or patients with impaired liver or kidney function, dose adjustment is not required