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 详细处方信息以本药内容附件PDF文件（201232019353139.pdf）的“原文Priscribing Information”为准
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部分中文法乐通处方资料（仅供参考）

法乐通（枸橼酸托瑞米芬片）|Fareston(Toremifene Tablets)
英文药名: Fareston (Toremifene Tablets)

中文药名: 法乐通（枸橼酸托瑞米芬片）

药品名称
【药品名称】
通用名称：枸橼酸托瑞米芬片
商品名称：法乐通
英文名称：Toremifene　Citrate　Tablets
【成份】
本品主要成份为枸橼酸托瑞米芬。
【性状】
本品为白色或灰白色片剂。

药理作用
药理作用：枸橼酸托瑞米芬是一种非类固醇类三苯乙烯衍生物，与同类其他药物例如三苯氧胺和克罗米芬相比，枸橼酸托瑞米芬与雌激素受体结合，可产生雌激素样或抗雌激素作用，或同时产生两种作用，这主要依赖疗程长短、动物种类、性别和靶器官的不同而定。一般来说，非类固醇类三苯乙烯衍生物在人和大鼠中主要表现为抗雌激素作用，在小鼠身上表现为雌激素样作用。绝经后乳癌患者应用托瑞米芬后引致血清总胆固醇和低密度脂蛋白（LDL）中度下降。枸橼酸托瑞米芬与雌激素竞争性地与乳腺癌细胞浆内雌激素受体相结合,阻止雌激素诱导的癌细胞DNA的合成及增殖。一些试验性肿瘤应用大剂量枸橼酸托瑞米芬，显示出枸橼酸托瑞米芬有非雌激素依赖的抗肿瘤作用。枸橼酸托瑞米芬的抗乳腺癌作用主要是抗雌激素作用,还可能有其它抗癌机制（改变肿瘤基因表达、分泌生长因子、诱导细胞凋亡及影响细胞动力学周期）。
毒理研究: 枸橼酸托瑞米芬的急性毒性低，小鼠和大鼠的LD50超过2000毫克/公斤。毒性研究表明致大鼠死亡原因是胃扩张。在急性和慢性的毒性研究中，大多数的发现是与枸橼酸托瑞米芬的激素样作用有关。而其它的发现无毒理学意义。枸橼酸托瑞米芬在大鼠身上未表现出任何致基因毒性，也未发现致癌作用。而雌激素可诱发小鼠卵巢和睾丸肿瘤，以及骨肥大和骨肉瘤。枸橼酸托瑞米芬在小鼠具有动物种类特殊的雌激素样作用并且引起同样的肿瘤。这些发现对枸橼酸托瑞米芬应用在人的安全性意义不大，因为枸橼酸托瑞米芬在人主要作用是抗雌激素。

药代动力学
a)一般特性:
枸橼酸托瑞米芬口服后被迅速吸收。3小时(介于2 - 5小时) 内血清达峰浓度。进食对吸收无影响但会使峰浓度延迟1.5 - 2小时出现。进食引起的变化无临床意义。血清浓度曲线可用两动相方程式来描述。第一相（分布）半衰期为4（介于2-12）小时，第二相（排泄）半衰期为5（介于2-10）天。由于缺少静脉给药的研究，体内基本分布数据（全身清除率CL及分布容积V）无法估计。枸橼酸托瑞米芬与血清蛋白(主要是白蛋白) 大量结合（99.5%）。每日口服枸橼酸托瑞米芬剂量在11-680毫克内，血清枸橼酸托瑞米芬药物动力学呈直线性动力。推荐剂量每日60毫克稳态血清浓度的平均枸橼酸托瑞米芬浓度为0.9 (介于0.6 - 1.3) 微克/毫升。枸橼酸托瑞米芬被广泛代谢。人血清中主要代谢产物为N-去甲基托瑞米芬，平均半衰期为11（介于4-20）日。其稳态浓度是原化合物的二倍。具有相似的抗雌激素作用，但不如原化合物抗肿瘤作用强。其与血清蛋白结合比托瑞米芬更为广泛(>99.9%)。血清中检测出三种次要代谢物: 去氨氢氧化托瑞米芬、4-氢氧化托瑞米芬、和N、N-二去甲基托瑞米芬。理论上这些代谢物都具有激素作用，但在枸橼酸托瑞米芬治疗过程中产出的浓度太低，因而不具有重要生物作用。枸橼酸托瑞米芬主要以代谢物从粪便中排出。可有肝肠循环。口服量约10%以代谢物的形式从尿中排泄。由于排泄缓慢，故血清中的稳态浓度要4至6周才可达到。
b)患者特点:
用推荐剂量每日60毫克时，临床疗效与血清浓度无正面关系。关于多种样式代谢无相关数据。枸橼酸托瑞米芬在人体中代谢所需酶系为细胞色素P450依赖肝复合氧化酶。主要代谢途经，N-去甲基化，的重要媒介为CYP3A。一项关于枸橼酸托瑞米芬药物动力学的开放性研究，将患者分成四平行组（每组10人）：正常人组、肝功能损害组（中位AST 57U/L、中位ALT 76U/L、中位r-GT 329U/L）或肝功能激活组（中位AST 25U/L、中位ALT 30U/L、中位r-GT 91U/L -这组患者用抗癫痫药治疗）和肾功能损害组（Cr 176μmol/L）。研究结果托瑞米芬药代动力学在肾功能损害组比正常人组中无明显变化。肝功能激活组托瑞米芬及其代谢物则排泄明显增加，而肝功能损害组则下降。

适应症
适用于治疗绝经后妇女雌激素受体阳性/或不详的转移性乳腺癌。

用法用量
推荐剂量为每日一次，每次1片(60毫克)。
肾功能不全患者: 不需调整剂量。
肝功能损害者: 应谨慎服用托瑞米芬(参见药代动力学）。 谨遵医嘱！

不良反应
常见的不良反应为面部潮红、多汗、子宫出血、白带、疲劳、恶心、皮疹、瘙痒、头晕、及抑郁。这些不良反应一般都为轻微，主要因为托瑞米芬的激素样作用。非常普遍（>1/10）,普遍（>1/100,1/1,000,1/10,000,<1/1,000），非常罕有（<1/10,000包括零散个别报告）血栓栓塞事件包括深静脉栓塞及肺栓塞（详见注意事项）用托瑞米芬治疗有肝酶水平改变（转氨酶升高）及在非常罕有情形下出现较严重肝功能异常（黄疸）。有几个报告在骨转移患者开始用托瑞米芬治疗有高血钙症。由于托瑞米芬的部份类雌激素作用,子宫内膜增厚可能在治疗期间发生.。子宫内膜的改变包括增生，息肉及肿瘤的风险增加。这可能是由于潜在的机制/类雌激素刺激有关（详见注意事项）。

禁忌
预先患有子宫内膜增生症或严重肝衰竭患者禁止长期服用枸橼酸托瑞米芬。禁用于已知对枸橼酸托瑞米芬及辅料过敏者。

注意事项
治疗前进行妇科检查，严谨检查是否已预先患有子宫内膜异常。之后最少每一年从复妇科检查。附加子宫内膜癌风险患者，例如高血压或糖尿病患者，肥胖高体重指数（>30）患者，或有用雌激素替代治疗历史患者应观密监测（参见不良反应）。既往有血栓性疾病历史的患者一般不接受枸橼酸托瑞米芬治疗（详见不良反应）。对非代偿性心功能不全及严重心绞痛患者要密切观察。骨转移患者在治疗刚开始时可能出现高钙血症，故对这类患者要观密监测。尚无系统性数据用于不稳定的糖尿病、严重功能状况改变或心衰竭患者。对驾驶及操作机械者能力的影响。

药物相互作用
未进行特别的相互作用研究。减少肾排泄钙的药物例如噻嗪类利尿剂可增加高钙血症。酶诱导剂例如苯妥英钠、苯巴比妥和卡马西平可加速托瑞米芬的排泄，使稳态血清浓度下降。出现这种情况时可能要将每日剂量加倍。已明确抗雌激素药物与法华令类抗凝血药物有协同作用引起出血时间严重增长。所以应避免与此类药物同时服用。理论上托瑞米芬的主要代谢途径为CYP3A酶系统，对该酶系统有抑制作用的药物例如酮康唑及类似的抗真菌药，红霉素和三乙酰夹竹桃霉素均可抑制托瑞米芬的代谢。故与此类药物同时应用要小心考虑。

孕妇及哺乳期妇女用药
枸橼酸托瑞米芬推荐用于绝经后妇女。由于缺乏人类在妊娠和哺乳期应用托瑞米芬的特别数据，所以此期妇女忌用枸橼酸托瑞米芬。动物生殖研究表明枸橼酸托瑞米芬可抑制生殖、诱导流产，并降低围产期胎儿的存活率。另外，在器官形成期用药可诱导骨化、使肋骨异常和胎儿浮肿。在大鼠，哺乳期用药可使其后代体重下降。

规格
60mg/片

Toremifene (Fareston®)
Toremifene
Toremifene is a hormonal therapy used to treat women with breast cancer who have been through the menopause (change of life). It is used to treat women whose cancer has spread to other areas of the body (secondary breast cancer). You will see your doctor regularly while you have this treatment so they can monitor its effects.

Hormonal therapies interfere with the production or action of particular hormones. Hormones are substances produced naturally in the body. They act as chemical messengers and help control the activity of cells and organs.

How it works
The way toremifene works is not yet fully understood, but its main function is as an anti-oestrogen drug. This means that it interferes with the action of the female hormone oestrogen.

Many breast cancers rely on the sex hormone oestrogen to grow. 

Hormone-sensitive breast cancers| have proteins called receptors on the breast cancer cells. They are known as 'oestrogen-receptor positive' (ER-positive) breast cancers. When oestrogen comes into contact with the receptors, it fits into them and stimulates the cancer cells to divide so that the tumour grows.

Toremifene fits into the oestrogen receptor and blocks oestrogen from reaching the cancer cells. This means the cancer either grows more slowly or stops growing altogether. Toremifene is most effective against ER-positive breast cancers.

How it is taken
Toremifene is a tablet that is taken once daily. It should be taken at approximately the same time each day.

Length of treatment
Your doctors will discuss the length of treatment they feel is appropriate for your situation. Toremifene may be given for as long as it is effective in controlling your cancer.

Possible side effects
Each person's reaction to any medicine is different. Some women have very few side effects while others may experience more.

We have outlined the most common side effects but haven't included those that are rare and therefore unlikely to affect you. If you notice any effects that are not listed here, discuss them with your doctor or nurse.

Hot flushes and sweats
These are a common side effect of toremifene. They may gradually lessen over the first few months, but some women continue to have them for as long as they take toremifene.

There are a number of ways to help to reduce or control hot flushes and sweats. Some women find it helpful to avoid or cut down on tea, coffee, nicotine and alcohol.

Some drugs, including low doses of some antidepressants or the hormone progesterone, may be helpful in controlling this side effect. Your nurse or doctor can discuss this with you.

Some women may find complementary therapies help. Your GP may be able to give you details about having these on the NHS.

You can read more about treatments for menopausal symptoms like hot flushes in our information about breast cancer and menopausal symptoms|.

You may have some of the following side effects, to varying degrees:

Feeling sick (nausea) and indigestion
Nausea| and indigestion| are fairly common but can often be relieved by taking your tablet with food or milk, or at night. Although nausea is quite common initially, it usually wears off after a few weeks.

Mood changes and tiredness (fatigue)
Toremifene may sometimes cause tiredness, dizziness and a low mood. Tell your doctor if you have these symptoms.

Vaginal bleeding or discharge
Let your doctor know if you have any vaginal bleeding or discharge.

Vision problems
Blurred or reduced vision is uncommon but let your doctor know about any changes to your eyesight.

Tumour flare
Women who are prescribed toremifene for cancer that has spread to the bones| may experience something called tumour flare when they start taking toremifene. This can cause a raised level of calcium in the blood (hypercalcaemia), with symptoms of nausea, vomiting and thirst. Occasionally, a short stay in hospital is needed until the calcium levels reduce.

Blood clots (thrombosis)
This is very rare. Signs of a blood clot include pain, warmth, swelling or tenderness in an arm or leg, or chest pain. Tell your doctor immediately if you have any of these signs. Toremifene isn't usually given to people who have had a blood clot in the past. 

Always let your doctor or nurse know about any side effects you have. There are usually ways in which they can be controlled or improved.

Long-term side effects
Studies have shown that women who take high doses of toremifene over a long period of time may have a very slightly increased risk of developing cancer of the lining of the womb (endometrial cancer|).

However, this small risk is generally outweighed by the benefits of taking toremifene. If detected early, treatment for endometrial cancer is usually very successful. An early warning sign is abnormal vaginal bleeding, although this is often caused by non-cancerous conditions such as polyps. If you have any abnormal vaginal bleeding, let your doctor know. Some women may have regular gynaecological check-ups.

Things to remember about toremifene tablets
Toremifene may interact with other medicines. Tell your doctor about any medication you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.
•Keep the tablets in a safe place, out of the reach of children.
•Keep the tablets in the original packaging and store them at room temperature, away from direct heat and sunlight.
•If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
•Don't worry if you forget to take your tablet. Do not take a double dose. The levels of the drug in your blood will not  change very much, but try not to miss  more than one or two tablets in a row.
•Remember to get a new prescription a few weeks before you run out of tablets and make sure you have plenty for holidays.

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 详细处方信息以本药内容附件PDF文件（201232019353139.pdf）的“原文Priscribing Information”为准
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