Tamoxifen (trade name: Nolvadex) is synthetic, non-steroidal drug with antiestrogen action. It works on the principle of competitive binding to estrogen receptors within the tumor cells. It results in inhibition of the synthesis and release of growth factors, as well as progesterone receptors stimulates the formation. This mechanism leads to inhibition of cell division of the large number of tumor estrogen receptors. Under the influence of tamoxifen for the additional increase in the concentration of specific binding globulin sex hormones, leading to a reduction in the concentration of free estradiol in plasma. The result is an increase in the secretion of FSH from the anterior pituitary gland that stimulates the ovaries to produce estrogen in premenopausal. It is believed that the transforming factor induces the release of TGF-β, further enhancing the antitumor effect of the drug. Treatment corresponds to approximately 34% of women with breast cancer at an advanced stage. Tamoxifen is well absorbed from the gastrointestinal tract. High concentration of drug in the blood occurs in 4-7 h after administration. In 99% bound to plasma proteins. t1/2 is 7-14 days. Tamoxifen is metabolized in the liver. Its main metabolite N-demetylotamoksyfen shows similar activity to tamoxifen. 65% of the drug is excreted as metabolites in the faeces.
Tamoxifen mode of action
Competitively inhibits the binding of hormone estrogen receptors in the cytoplasm, resulting in limited cell division of estrogen-dependent tissues. In metastatic breast cancer the complete or partial remission, especially in soft tissue metastases and bone, occurs in about 50-60% of cases, if the tumor tissue are estrogen receptors, and only about 10% of the cases, the absence of these receptors. Tumors in women with estrogen receptor positive or unknown tumors receptor status, adjuvant therapy have received tamoxifen, there was a significantly fewer relapses and increased the percentage of 10-year survival. Tamoxifen is well absorbed from the gastrointestinal tract. The maximum serum concentration is achieved 4-7 hours after oral administration. It is extensively metabolized. Tamoxifen and its transformation products accumulate in the liver, lungs, brain, pancreas, skin and bones. Tamoxifen is excreted mainly in the faeces in the form of various metabolites.
The main tamoxifen goal is treatment of breast cancer in pre and after menopausal women. Tamoxifen is the drug of choice in patients who underwent radical surgery after 60 years of age, diagnosed with lymph node metastasis. In premenopausal women, tamoxifen may be an alternative oophorectomy or ovarian irradiation. Also used to reduce the risk of breast cancer in women with breast cancer in situ after surgery and radiotherapy or belonging to groups at high risk. It can also be used (according to some authors) in the induction of ovulation, the treatment of mastalgia and mastitis.
The fact that tamoxifen is used to treat breast cancer have also been mentioned by bodybuilders, especially in a situation when bodybuilder is affected by gynecomastia. Operation in this case, by blocking the estrogen receptors in the vicinity of the breast and thus subject to aromatization of androgen excess does not adversely affect the area of the body.
Hypersensitivity to any component of the formulation. Consider the benefit-risk ratio in patients with thromboembolic disease in an interview. Caution in patients with leukopenia, thrombocytopenia, must be monitored periodically blood counts.
Tamoxifen enhances the effects of oral anticoagulants of the coumarin group. Concomitant therapy with other hormones diminish the effects of tamoxifen. The use of tamoxifen with cytotoxic agents may increase the risk of thromboembolic complications. Co-administration of mitomycin C increases the risk of thrombocytopenia, anemia, and renal failure. In combination with bromocriptine increased plasma concentrations of tamoxifen and its metabolites.
Are relatively rare. Reducing the dose can frequently continue treatment. The most common side effects include vasomotor symptoms associated with estrogen deficiency: flushing, hot flashes; rash, nausea, vomiting, dizziness, headache, menstrual disorders, vaginal bleeding, vaginal discharge, severity of pain in cancer lesions and bone pain.
Dosing and Administration
Typically, 20 mg once daily or 2 doses x 10 mg. Maximum daily dose should not exceed 40 mg. Induction of ovulation on day 5 of cycle 2 × 10 mg for 10 days; in the event of treatment failure in the first cycle can be used in the next higher dose – 40 mg / d in the second cycle and 80 mg / d in the third. For mastalgia and mastopathy: 20 mg daily. In the case of ovulation induction, mastitis and mastalgia treatment results are not conclusive.