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 部分中文他莫昔芬处方资料（仅供参考）

药品名称（包括商品名、通用名）
他莫昔芬 

用法用量
①乳腺癌等肿瘤：开始10mg，2次／d，口服。如1个月内无效，可增至20mg，2次／d。若80mg／d仍无效，再增剂量亦无意义；②不孕症：于月经周期第2～5天服10mg，2次／d，如果需要；以后周期可用至40mg，2次／d。 

药理作用
本品是三苯乙烯非甾体抗雌激素类药物的典型代表。它能与雌二醇竞争与雌激素受体结合。当其与雌激素受体结合后，可诱导改变受体的三维空间形状，阻止受体与DNA上的雌激素反应成分相结合，使转录等过程不能进行，从而抑制激素依赖性乳腺肿瘤细胞的生长。近来研究表明，本品的抗癌作用可能还有其他机制，如：诱导癌细胞的周围细胞分泌生长抑制因子TGF-β，减少周围组织局部产生胰岛素样生长因子（IGF-1），该因子是一种乳腺癌细胞的胰生长因子。此外，本品还具有抑制蛋白激酶C和钙调蛋白依赖性cAMP磷酸二酯酶的作用，也能保护细胞膜和脂蛋白免受氧化损伤。除与雌激素受体作用外，本品也作用于其他生物大分子，尤其是对钙调素有拮抗作用，可延缓停经妇女骨质疏松的发生。本品还可降低血清胆固醇，降低低密度脂蛋白，减少心肌梗死发生的危险。本品为雌激素拮抗剂，能与雌二醇竞争靶细胞内雌激素受体的结合，从而阻断雌二醇的作用。此外，还能抑制细胞生长因子的产生和释放。
 
适应症
用于治疗晚期播散性乳腺癌，是停经后晚期乳腺癌的首选药物。本品对晚期卵巢癌、宫体癌等实体瘤也有效。还可用于晚期前列腺癌、晚期黑色素瘤、晚期肾癌、晚期胰腺癌。最近开始治疗脑瘤和肝癌。对绝经期妇女的疾病如乳腺癌、骨质疏松和心脏病等有预防作用。也可用其诱发排卵作用治疗不孕症。主要用于早期乳腺癌手术后的辅助治疗及晚期乳腺癌的姑息治疗，对雌激素受体水平高者疗效好，水平低者疗效很差。还用于治疗另一些恶性肿瘤：如卵巢癌、子宫内膜癌、肾癌和黑色素瘤。此外，亦用于无排卵性不育症。 

不良反应
常见的不良反应有面部潮红、恶心、呕吐等，发生率约25%。较少见的有月经不规则、阴道出血、白带增多、外阴瘙痒和皮炎等。高剂量长期应用可致视力障碍，故眼药期间应定期作眼科检查。本品尚有部分雌激素激动作用，长期应用可引起继发性子宫内膜肿瘤。接受20mg/d治疗2年的患者，其肿瘤发生率至少比未用本品的对照组高2倍以上。因此，接受本品治疗者至少应每年进行盆腔检查和其他有关检查。本品还能增加其栓形成的危险。
 
制剂
片剂：每片含枸椽酸他莫昔芬15.2mg相当于他莫昔芬10mg。
 
注意事项
有月经的妇女慎用，以免引起月经不规则和卵巢囊肿增大，孕妇禁用。 

Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as 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 treatment
Tamoxifen is currently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women. Additionally, it is the most common hormone treatment for male breast cancer. It is also approved by the FDA for the 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 studies
In 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, but after 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.[9] 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.[10] 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.[11][12]

Other uses
McCune-Albright syndrome
In 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).[13][14][15] 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.

Infertility
Tamoxifen 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.[19] In addition, a rare condition occasionally treated with tamoxifen is retroperitoneal fibrosis.

Gynecomastia
Tamoxifen 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 disorder
Tamoxifen 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 cancer
Tamoxifen 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. Clinical trials 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.[24] Furthermore tamoxifen treatment alone has been 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 expression
Tamoxifen is used as a research tool to trigger tissue specific gene expression in many conditional expression constructs in genetically modified animals including a version of the Cre-Lox recombination technique.

Riedel's thyroiditis
Tamoxifen has been proposed as part of a treatment plan for Riedel's thyroiditis.

Mechanism of action
Tamoxifen competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that decreases DNA synthesis 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 the liver 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 as co-repressors to stop genes being switched on by estrogen. Some of these proteins include NCoR and SMRT. Tamoxifen function can be regulated by a number of different variables including growth factors.Tamoxifen needs to block growth factor proteins such as ErbB2/HER2[33] 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 effects
A 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 also increase the risk of adverse side effects.

Bone
A 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.[38][39] 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 observed clinically. Hence tamoxifen's tissue selective action directly led to the formulation of the concept of selective estrogen receptor modulators (SERMs).[40] In contrast tamoxifen appears to be associated with bone loss in premenopausal women who continue to menstruate after adjuvant chemotherapy.

Endometrial cancer
Tamoxifen is a selective estrogen receptor modulator. Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore endometrial changes, including cancer, are among tamoxifen's side effects.[43] 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 cancer while lowering the risk of breast cancer recurrence. The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

Cardiovascular and metabolic
Tamoxifen 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.[46] For some women, tamoxifen can cause a rapid increase in triglyceride concentration in the blood.[citation needed] 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 system
Tamoxifen-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 fusion
While tamoxifen has been shown to antagonize the actions of estrogen in tissues such as the breast, its effects in other tissues such as bones 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.

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 详细处方信息以本药内容附件PDF文件（201252421424119.PDF）的“原文Priscribing Information”为准
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