口服有效的抗前列腺增生药物西洛多辛在美国上市

FDA 于2008年10月4日批准Watson 公司 的silodosin胶囊 (Rapaflo) 用于改善良性前列腺增生（也称为前列腺肥大）（BHP）引起的症状。良性前列腺增生在50岁男性中的发病率为50%，在80年男性中的发病率升高至75%。本品通过阻断前列腺、膀胱、输尿管中的肾上腺α1受体而起作用，通过阻断这些受体，使得在这些组织中的平滑肌得以放松，从而减轻前列腺增生的症状。

本品为一日1次的胶囊剂，针对无肝肾功能损伤患者的服用剂量为8mg/天，轻中度肝肾功能损伤患者的服用剂量是4mg/天，本品不推荐在重度肝肾功能损伤的患者中使用。两项纳入923例患者为期12周的随机双盲安慰剂对照的多中心临床研究结果表明：本品与安慰剂相比对BHP症状的改善情况与小便通畅率的改善均有显著的统计学意义。

本品的主要不良反应为在性高潮期间没有精液排除或者精液排除减少。但这一不良反应不会纳入对本品的安全性考虑，其他的不良反应还包括眩晕，头昏，腹泻，体位性高血压，头痛，鼻咽炎，鼻充血等。

【产品名称】西洛多辛; 西罗多辛; 2,3-二氢-1-(3-羟基丙基)-5-[(2R)-2-[2-[2-(2,2,2-三氟乙氧基)苯氧基]乙胺基]丙基]-1H-吲哚-7-甲酰胺

【英文别名】1-(3-Hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2,3-dihydro-1H-indole-7-carboxamide

【适应症】治疗由于前列腺良性增生所致的排尿困难。

【规格】4mg，8mg
分子式：C25H32F3N3O4分子量：582.65
CAS登记号：160970-54-7

【简介】
西罗多辛（Silodosin）为α1肾上腺素受体拮抗剂，临床上用于治疗由于前列腺良性增生所致的排尿困难。
良性前列腺增生（BPH）是老年男性常见病之一，以前列腺的非恶性增大为特征。在60岁或以上的老年人中有50%以上患有此症，而在85岁及以上的老年人中有90%以上者发病。其发病原因尚未阐明，一般认为与性激素和胆固醇等的分泌、代谢失调有关。有人认为，老年人因垂体－促性腺激素－睾丸的作用途径减弱或因内源性变化，使睾丸退化、性机能下降、睾酮值降低、前列腺因结缔组织增多，使腺上皮改变、前列腺增大。前列腺的增大会压迫尿道，导致膀胱尿流不畅，甚至堵塞膀胱出口。在人类前列腺中存在α1A-肾上腺素受体，该受体的激活会加重尿道梗阻和排尿困难症状。因此，通过阻断α1A-肾上腺素受体的结合，可使梗阻的前列腺平滑肌松弛，从而改善症状。
良性前列腺增生（BPH）是老年男性常见病之一，以前列腺的非恶性增大为特征。在60岁或以上的老年人中有50%以上患有此症，而在85岁及以上的老年人中有90%以上者发病。其发病原因尚未阐明，一般认为与性激素和胆固醇等的分泌、代谢失调有关。有人认为，老年人因垂体－促性腺激素－睾丸的作用途径减弱或因内源性变化，使睾丸退化、性机能下降、睾酮值降低、前列腺因结缔组织增多，使腺上皮改变、前列腺增大。前列腺的增大会压迫尿道，导致膀胱尿流不畅，甚至堵塞膀胱出口。在人类前列腺中存在α1A-肾上腺素受体，该受体的激活会加重尿道梗阻和排尿困难症状。因此，通过阻断α1A-肾上腺素受体的结合，可使梗阻的前列腺平滑肌松弛，从而改善症状。
与对所有α-受体亚型均有高亲和常数的（pKD＞9）哌唑嗪和坦索罗辛（tamsulosin，已上市用于前列腺增生引起的排尿障碍）比较，Silodosin（10-2000pmol/L）仅对α1A-肾上腺素受体有较高的亲和力（pKD＝10.5），而对α1B-及α1D-肾上腺素受体的亲和力不明显。竞争性结合试验也显示，[3H]－Silodosin对α1A-受体亚型具有高的缔合能力（pKi＝10.4）比对α1B（pKi＝8.1）和α1D（pKi＝8.6）高。[3H]-Silodosin对鼠颌下腺的α1A受体亚型表现出高亲和力，而对鼠肝的α1B受体亚型无亲和力。
有关裸鼠组织的结合实验研究表明：Silodosin在肝中（Ki=16 nmol/L）和颌下腺中(Ki=0.15 nmol/L)的抑制曲线符合单室模型，而在心肌膜上则即有低亲和、也有高亲和的结合位点。
对表达α1A受体亚型的CHO细胞，Silodosin能抑制去甲肾上腺素引起的细胞内Ca2+浓度增加，其IC50为(0.32±0.05）nmol/L；而对表达α1B和α1D的CHO细胞的作用较弱，即使高浓度的药物也不能起到完全抑制作用。此外，实验表明，与[3H]－哌唑嗪相比，[3H]－Silodosin对人的主要含α1A受体亚型的前列腺膜的亲和力更高；而且，Silodosin对人的前列腺的亲和力比对含α1B受体亚型的主动脉样本的亲和力高出200倍。
有人采用经脑干横切术消除大脑功能的实验犬为对象，比较了Silodosin、坦索罗辛和哌唑嗪对电刺激下腹神经引起的犬尿道压力增加的抑制作用。结果表明，静脉给药后，Silodosin对尿道的选择性作用分别比哌唑嗪高12倍，比坦索罗辛高7.5倍。Silodosin能明显抑制去甲肾上腺素引起的人前列腺收缩（K＝9.45±0.025），药效与坦索罗辛相当，而比哌唑嗪更强。Silodosin与人体前列腺的亲和力比其对人肠系膜动脉的亲和力高100倍。
Silodosin对BPH大鼠模型的膀胱活动亢进有剂量依赖性的抑制作用，并能提高膀胱收缩的压力阈。这表明本品除能改善膀胱功能外，对BPH的刺激症状也有改善作用。
在对药物与α1受体的结合程度进行评估时，采用了有关Silodosin与人和大鼠体内前列腺α1受体结合的有关参数。结果表明，口服用药0.5～6小时后，被药物结合的α1受体比率在60%～90%范围内，24小时后降为40%。

【原产地英文商品名】RAPAFLO 4mg/cap 30caps/bottle
【原产地英文药品名】 SILODOSIN
【中文参考商品译名】
注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
·RAPAFLO 4mg/cap 30caps/bottle
·RAPAFLO 8mg/cap 30caps/bottle
·RAPAFLO 8mg/cap 90caps/bottle
【中文参考药品译名】西罗多辛
【生产厂家中文参考译名】 华生制药
【生产厂家英文名】 WATSON LABS 

Rapaflo
Generic Name: silodosin (SIL oh DOE sin)
Brand Names: Rapaflo

------------------------------------------------------

What is Rapaflo?
Rapaflo (silodosin) belongs to a group of drugs called alpha-adrenergic blockers. Rapaflo helps relax the muscles in the prostate and bladder neck, making it easier to urinate.

Rapaflo is used to improve urination in men with benign prostatic hyperplasia (enlarged prostate).

Rapaflo may also be used for other purposes not listed in this medication guide.

------------------------------------------------------

Important information about Rapaflo
You should not take Rapaflo if you have severe kidney or liver disease, or if you are also using ketoconazole (Extina, Ketozole, Nizoral, Xolegal), itraconazole (Sporanox), or ritonavir (Norvir).

Do not take Rapaflo with other similar medicines such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), tamsulosin (Flomax), or terazosin (Hytrin).

Rapaflo may cause dizziness or fainting, especially when you first start taking it. Be careful if you drive or do anything that requires you to be alert. Avoid standing for long periods of time or becoming overheated during exercise and in hot weather. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Rapaflo can affect your pupils during cataract surgery. Tell your eye surgeon ahead of time that you are using Rapaflo. Do not stop using Rapaflo before surgery unless your surgeon tells you to.

There are many other drugs that can interact with Rapaflo. Tell your doctor about all medications you use.

------------------------------------------------------

Before taking Rapaflo
You should not take Rapaflo if you are allergic to silodosin, or if you have:
severe kidney disease;
severe liver disease; or
if you are also using ketoconazole (Extina, Ketozole, Nizoral, Xolegal), itraconazole (Sporanox), or ritonavir (Norvir).

Do not take Rapaflo with other similar medicines such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), tamsulosin (Flomax), or terazosin (Hytrin).

If you have liver or kidney disease or a history of prostate cancer, you may need a Rapaflo dose adjustment or special tests to safely take this medication.

Rapaflo can affect your pupils during cataract surgery. Tell your eye surgeon ahead of time that you are using this medication. Do not stop using Rapaflo before surgery unless your surgeon tells you to.

Although Rapaflo is not for use in women, silodosin is not expected to harm an unborn baby. If you are a woman using this medication, tell your doctor if you are pregnant or breast-feeding. Rapaflo is not for use in children.

------------------------------------------------------

How should I take Rapaflo?
Take Rapaflo exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Rapaflo is usually taken once daily with a meal. Rapaflo lowers blood pressure and may cause dizziness or fainting, especially when you first start taking it. Call your doctor if you have severe dizziness or feel like you might pass out.

You may feel very dizzy when you first wake up. Be careful when standing or sitting up from a lying position.

Your blood pressure and prostate will need to be checked often. Visit your doctor regularly.

Some things can cause your blood pressure to get too low. This includes vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Store Rapaflo at room temperature away from moisture, heat, and light.

------------------------------------------------------

What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

------------------------------------------------------

What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include extreme dizziness or fainting.

------------------------------------------------------

What should I avoid while taking Rapaflo?
Rapaflo may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

To prevent dizziness, avoid standing for long periods of time or becoming overheated during exercise and in hot weather.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. Drinking alcohol can increase certain side effects of Rapaflo.

------------------------------------------------------

Rapaflo side effects
Get emergency medical help if you have any of these signs of an allergic reaction to Rapaflo: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using Rapaflo and call your doctor at once if you have a serious side effect such as:
feeling like you might pass out; or
penis erection that is painful or lasts 4 hours or longer.

Less serious Rapaflo side effects may include:
mild dizziness;
headache;
diarrhea;
abnormal ejaculation; or
runny or stuffy nose, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

------------------------------------------------------

What other drugs will affect Rapaflo?
Tell your doctor about all other medications you use, especially:
conivaptan (Vaprisol);
imatinib (Gleevec);
isoniazid (for treating tuberculosis);
quinidine (Quin-G);
an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), or telithromycin (Ketek);
an antidepressant such as nefazodone;
antifungal medication such as clotrimazole (Mycelex Troche) or voriconazole (Vfend);
erectile dysfunction medicine such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra);
heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others;
HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), or nelfinavir (Viracept), saquinavir (Invirase); or
medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf).

This list is not complete and there are many other drugs that can interact with Rapaflo. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

------------------------------------------------------

Where can I get more information?
Your pharmacist can provide more information about Rapaflo.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.