所属类别： 20毫克/片 60片/盒
包装规格： 20毫克/片 60片/盒
原产地英文商品名：TAMOXIFENO FARMOZ 20MG/TAB 60TABS/BOX
中文参考商品译名：TAMOXIFENO FARMOZ 20毫克/片 60片/盒
TamoxifenTamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues suchas the endometrium, it behaves as an agonist, and thus may be characterized as a mixed agonist/antagonist. Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre-menopausal women, and is also a standard in post-menopausal women although aromatase inhibitors are also frequently used in that setting.Some breast cancer cells require estrogen to grow. Estrogen binds to and activates the estrogen receptor in these cells.Tamoxifen is metabolized into compounds that also bind to the estrogen receptor but do not activate it. Because of this competitive antagonism, tamoxifen acts like a key broken off in the lock that prevents any other key from being inserted, preventing estrogen from binding to its receptor. Hence breast cancer cell growth is blocked.Tamoxifen was discovered by pharmaceutical company Imperial Chemical Industries (now AstraZeneca) and is sold under the trade names Nolvadex, Istubal, and Valodex. However, the drug, even before its patent expiration, was and still is widely referred to by its generic name “tamoxifen.”Breast cancer treatmentTamoxifen is currently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- andpost-menopausal women. Additionally, it is the most common hormone treatment for male breast cancer. It is also approved by the FDA forthe prevention of breast cancer in women at high risk of developing the disease. It has been further approved for the reduction of contralateral (in the opposite breast) cancer.Comparative studiesIn 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, butafter an average 4-year follow-up there were 36% fewer uterine cancers and 29% fewer blood clots in women taking raloxifene than in women taking tamoxifen, although the difference is not statistically significant.In 2005, the ATAC trial showed that after average 68 months following a 5 year adjuvant treatment, the group that received anastrozole (Arimidex) had significantly better results than the tamoxifen group in measures like disease free survival, but no overall mortality benefit. Data from the trial suggest that anastrozole should be the preferred medication for postmenopausal women with localized breast cancer that is estrogen receptor (ER) positive. Another study found that the risk of recurrence was reduced 40% (with some risk of bone fracture) and that ER negative patients also benefited from switching to anastrozole.Other usesMcCune-Albright syndromeIn McCune-Albright syndrome (MAS) tamoxifen has been used to treat premature puberty and the consequences of premature puberty.Tamoxifen has been seen to decrease rapid bone maturation which is the result of excessive estrogen and improve predicted adult height(PAH). The same effects have also been seen in short pubertal boys.However, one in vitro study in 2007 and later an in vivo study in 2008 have shown that tamoxifen induces apoptosis in growth plate chondrocytes, reduces serum IGF-I levels and causes persistent retardation of longitudinal and cortical radial bone growth in young male rats, leading the researches to express concern giving tamoxifen to growing individuals.InfertilityTamoxifen is used to treat infertility in women with anovulatory disorders. A dose of 10–40 mg per day is administered in days 3–7 of a woman’s cycle. In addition, a rare condition occasionally treated with tamoxifen is retroperitoneal fibrosis.GynecomastiaTamoxifen is used to prevent estrogen related gynecomastia, resulting from elevated estrogenic levels. It is taken as a preventative measure in small doses, or used at the onset of any symptoms e.g. nipple soreness/sensitivity. Other drugs are taken for the similar purposeses such as clomiphene citrate and the anti-aromatase drugs which are used in order to try to avoid the hormone related adverse effects.Tamoxifen is also sometimes used to treat or prevent gynecomastia in sex offenders undergoing temporary chemical castration.Bipolar disorderTamoxifen has been shown to be effective in the treatment of mania in patients with bipolar disorder by blocking protein kinase C (PKC), an enzyme that regulates neuron activity in the brain.Researchers believe PKC is over-active during the mania in bipolar patients.Angiogenesis and cancerTamoxifen is one of three drugs in an anti-angiogenetic protocol developed by Dr. Judah Folkman, a researcher at Children’s Hospital at Harvard Medical School in Boston. Folkman discovered in the 1970s that angiogenesis – the growth of new blood vessels – plays a significant role in the development of cancer. Since his discovery, an entirely new field of cancer research has developed. Clinicaltrials on angiogenesis inhibitors have been underway since 1992 using myriad different drugs. The Harvard researchers developed a specific protocol for a golden retriever named Navy who was cancer-free after receiving the prescribed cocktail of celecoxib, doxycycline, and tamoxifen – the treatment subsequently became known as the Navy Protocol. Furthermore tamoxifen treatment alone hasbeen shown to have anti-angiogenetic effects in animal models of cancer which appear to be, at least in part, independent of tamoxifen’s estrogen receptor antagonist properties.Control of gene expressionTamoxifen is used as a research tool to trigger tissue specific gene expression in many conditional expression constructs in geneticallymodified animals including a version of the Cre-Lox recombination technique.Riedel’s thyroiditisTamoxifen has been proposed as part of a treatment plan for Riedel’s thyroiditis.Mechanism of actionTamoxifen competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that decreases DNAsynthesis and inhibits estrogen effects. It is a nonsteroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in breast and other tissues.Tamoxifen causes cells to remain in the G0 and G1 phases of the cell cycle. Because it prevents (pre)cancerous cells from dividing but does not cause cell death, tamoxifen is cytostatic rather than cytocidal.Tamoxifen itself is a prodrug, having relatively little affinity for its target protein, the estrogen receptor. It is metabolized in theliver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen (afimoxifene) and N-desmethyl-4-hydroxytamoxifen (endoxifen)which have 30-100 times more affinity with the estrogen receptor than tamoxifen itself.These active metabolites compete with estrogen in the body for binding to the estrogen receptor. In breast tissue, 4-hydroxytamoxifen acts as an estrogen receptor antagonist so that transcription of estrogen-responsive genes is inhibited.Tamoxifen binds to estrogen receptor (ER) which in turn interacts with DNA. The ER/tamoxifen complex recruits other proteins known asco-repressors to stop genes being switched on by estrogen. Some of these proteins include NCoR and SMRT.Tamoxifen function canberegulated by a number of different variables including growth factors.Tamoxifen needs to block growth factor proteins such as ErbB2/HER2 because high levels of ErbB2 have been shown to occur in tamoxifen resistant cancers. Tamoxifen seems to require a protein PAX2 for its full anticancer effect.In the presence of high PAX2 expression, the tamoxifen/estrogen receptor complex is able to suppress the expression of the pro-proliferative ERBB2 protein. In contrast, when AIB-1 expression is higher than PAX2, tamoxifen/estrogen receptor complex upregulates the expression of ERBB2 resulting in stimulation of breast cancer growth.Side effectsA report in September 2009 from Health and Human Services’ Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but alsoincrease the risk of adverse side effects.BoneA beneficial side effect of tamoxifen is that it prevents bone loss by acting as an estrogen receptor agonist (i.e., mimicking the effects of estrogen) in this cell type. Therefore, by inhibiting osteoclasts, it prevents osteoporosis. When tamoxifen was launched as a drug, it was thought that tamoxifen would act as an estrogen receptor antagonist in all tissue, including bone, and therefore it was feared that it would contribute to osteoporosis. It was therefore very surprising that the opposite effect was observedclinically. Hence tamoxifen’s tissue selective action directly led to the formulation of the concept of selective estrogen receptor modulators (SERMs). In contrast tamoxifen appears to be associated with bone loss in premenopausal women who continue to menstruate after adjuvant chemotherapy.Endometrial cancerTamoxifen is a selective estrogen receptor modulator. Even though it is an antagonist in breast tissue it acts as partial agonist on theendometrium and has been linked to endometrial cancer in some women.Therefore endometrial changes, including cancer, are among tamoxifen’s side effects. With time, risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for 5 years.The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine cancerwhile lowering the risk of breast cancer recurrence. The ACS states that its use should not be avoided in cases where the risk of breastcancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.Cardiovascular and metabolicTamoxifen treatment of postmenopausal women is associated with beneficial effects on serum lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect. For some women, tamoxifen can cause a rapid increase in triglyceride concentration in the blood. In addition there is an increased risk of thromboembolism especially during and immediately after major surgery or periods of immobility.Tamoxifen is also a cause of fatty liver, otherwise known as steatorrhoeic hepatosis or steatosis hepatis.Central nervous systemTamoxifen-treated breast cancer patients show evidence of reduced cognition, a major side effect of tamoxifen, and semantic memory scores.However memory impairment in patients treated with tamoxifen was less severe compared with those treated with anastrozole (an aromatase inhibitor).A significant number of tamoxifen treated breast cancer patients experience a reduction of libido.Premature growth plate fusionWhile tamoxifen has been shown to antagonize the actions of estrogen in tissues such as the breast, its effects in other tissues such asbones has not been documented fully. There have been studies done in mice showing tamoxifen mimic the effects of estrogen on bone metabolism and skeletal growth. Thus increasing the possibility of pre-mature bone fusion. This effect would be less of a concern in adults who have stopped growing.