【英文名】Tizanidine Hydrochloride

【主要成分】
本品主要成份为盐酸替扎尼定，其化学名为5-氯-4-(2-咪唑啉-2氨基)-2,1,3-苄硫噻嗪盐酸盐，
别名 5-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl);

【药理毒理】
药理作用 替扎尼定为中枢性α2肾上腺素受体激动剂，可能是通过增强运动神经元的突触前抑制作用而降低强直性痉挛状态。动物实验显示，替扎尼定对骨骼肌纤维和神经肌肉接头没有直接作用，对单突触脊髓反射的作用弱。替扎尼定对多突触通路的作用最强，这些作用被认为与脊髓运动神经元的易化性降低有关。
毒理研究
遗传毒性:
替扎尼定Ames试验、哺乳动物基因突变试验、中国仓鼠细胞染色体畸变试验、小鼠骨髓微核试验、中国仓鼠骨髓微核试验和细胞遗传学试验、小鼠显性致死诱变试验和小鼠程序外DNA合成试验结果均为阴性。
生殖毒性: 雄性大鼠给予替扎尼定10mg/kg，雌性大鼠3mg/kg(以mg/m2计算，分别相当于人最大推荐剂量的2.7倍和1倍)，未见对生育力的影响。雄性大鼠给予替扎尼定30mg/kg、雌性大鼠10mg/kg时，生育力下降，母体出现镇静、体重减轻和运动失调等症状。大鼠给予替扎尼定3mg/kg、家兔30mg/kg(以mg/m2计算，分别相等于人最大推荐剂量的1倍和16倍)，未见致畸作用。给予1～8倍于人最大推荐剂量的替扎尼定可延长大鼠的妊娠期，导致围产期幼鼠丢失增加、发育迟缓。家兔给予替扎尼定1mg/kg及更高剂量下，胚胎着床后丢失增加。
致癌性: 小鼠经口给予替扎尼定剂量达16mg/kg，连续78周，大鼠经口给予替扎尼定剂量达9mg/kg，连续104周(按mg/m2计算，分别相当于人最大推荐剂量的2倍和2.5倍)，肿瘤发生率均未见显著增加。

【药代动力学】
盐酸替扎尼定口服吸收良好，其绝对口服生物利用度约为40%(变异系数CV=24%)。口服后达峰浓度的时间为1.5h(CV=40%)；食物可使口服该药后的血药浓度峰值(Cmax)增加近1/3，使达峰时间缩短近40min，但是并不影响胃肠道对该药的总吸收。盐酸替扎尼定在体内分布广泛，健康志愿者静脉给药达稳态时的Vd为2.4L/kg(CV=21%)。该药与血浆蛋白结合率约为30%，且在治疗剂量范围内无明显浓度依赖性。肝脏对该药的首过消除作用较大，给药后约95%的药物经肝脏代谢，代谢产物无明显活性。盐酸替扎尼定血浆消除半衰期(T1/2)约为2.5h(CV=33%)，其代谢产物的T1/2为20-40h。约20%的盐酸替扎尼定经肠道排出，60%以上的药物经肾脏排泄，其中原形排泄物仅为3%。肾功能不良明显影响该药的排泄；当肌酐清除率小于1.5L/h时，肾脏对该药的排泄速度降低50%以上，使该药的血浆消除半衰期平均延长达13.6h。

【适应症】
盐酸替扎尼定片为中枢性骨骼肌松驰药，用于:
(1)下列疾病造成的疼痛性肌痉挛的改善
——颈、肩及腰部疼痛等局部疼痛综合征
(2)下列疾病引起的中枢性肌强直
——脑血管意外、手术后遗症(脊髓损伤、大脑损伤)、脊髓小脑变性、多发性硬化症、肌萎缩性侧索硬化症等

【用法用量】
用于疼痛性肌痉挛时:
口服2mg/次，每天3次。并根据年龄、症状酌情增减。
用于中枢性肌强直时:
应根据患者需要而作剂量调整。初始剂量不应超过6mg/天(分三次服用)，并可每隔半周或一周逐渐增加2－4mg。通常12－24mg/天(分3－4次服用)的用量已可获得良好的疗效；每天的总量不能超过36mg。

【不良反应】
据文献报道:
1、导致治疗终止的一般性的不良事件:在多剂量，安慰剂对照的临床研究中，264名病人给予替扎尼定，261名给予安慰剂，药物处理组中包括几种严重的不良事件在内的不良反应的发生比安慰剂对照组频率更高。
多剂量安慰剂对照研究中，由于不良反应的发生而中途停止给药的患者在接受替扎尼定治疗的264名病人中有45名(17%)，给予安慰剂的261名患者中有13名(5%)。当退出治疗后，他们常常叙述有2个或以上的停止服药的理由。导致停药的最常出现的不良事件有:疲乏(3%)，嗜睡(3%)，口干(3%)，痉挛程度或张力增加(2%)和头昏(2%)。其中，乏力，嗜睡/镇静，口干和头昏为最常发生的与替扎尼定相关的不良事件，有3/4的病人认为这些不良事件是轻度-中度，1/4的病人认为很严重；这些不良事件有剂量依赖性。
2、单剂量给予安慰剂对照的142名受试者参与的研究中，除了上述最常见的不良事件之外，还有低血压和心动过缓(发生率＞2%)。
3、研究中观察到的其他不良反应:在另外的1187例病人临床研究中观察替扎尼定的不良事件。这些研究，有的是随机双盲，有的是开放研究；有的为安慰剂对照研究，有的则未设立对照组；有的为门诊病人，有的为住院病人；有的采用逐渐增量的给药方案。最后的统计结果，以COSTART原则为标准，分为全身不良事件和各系统的不良事件。常见不良事件发生指发生率超过1/100，少见不良事件指发生率在1/100～1/1000之间，罕见的不良事件指发生率在1/1000。应该指出的是，尽管这些不良事件发生于替扎尼定治疗过程中，但是不一定是由该药引起。
(1)全身的不良事件:常见的:发热；少见的:变态反应，念珠菌病，不适，脓肿，颈痛，败血症，死亡；罕见的:癌症，先天性畸性，自杀倾向。
(2)心血管系统:少见的:血管扩张，体位性低血压，晕厥，偏头痛，心律失常；罕见的:心绞痛，冠状动脉疾患，心衰，心肌梗塞，静脉炎，肺栓塞，室早和室速。
(3)消化系统:常见的:腹痛，腹泻，消化不良；少见的:吞咽困难，胆结石，粪便嵌塞，胃肠胀气，黑便，胃肠出血，肝炎；罕见的:呕血，胃肠炎，肝癌，小肠梗阻，肝损害。
(4)血液淋巴系统:少见的:瘀斑，高胆固醇血症，贫血，高脂血症，白细胞减少症，白细胞增多症，败血症；罕见的:瘀点，紫癜，血小板减少症，血小板增多症。
(5)营养和代谢系统:少见的:水肿，甲状腺功能低下，体重减轻；罕见的:肾上腺皮质机能不全，高血糖症，高钾血症，低钠血症，低蛋白血症和呼吸性酸中毒。
(6)骨骼肌系统:常见的:肌无力，背痛；少见的:病理性骨折，关节痛，关节炎和滑囊炎。
(7)神经系统:常见的:抑郁，焦虑，感觉异常；少见的:震颤，情绪不稳定，惊厥，麻痹，思维异常，眩晕，怪梦，激动不安，丧失自我感，欣快感，偏头痛，感觉丧失，自主神经功能失调，神经痛；极少见的:痴呆，神经病。
(8)呼吸系统:少见的:鼻窦炎，肺炎，支气管炎，罕见的:哮喘。
(9)皮肤及附属器官:常见的:皮疹，出汗，皮肤溃疡；少见的:瘙痒，皮肤干燥，痤疮，秃头，荨麻疹；罕见的:表皮剥脱，皮炎，单纯疱疹，带状疱疹，皮肤癌。
(10)特殊感觉:少见的:耳痛，耳鸣，耳聋，青光眼，结合膜炎，眼痛，视神经炎，中耳炎，视网膜出血，视野缺损；罕见的:虹膜炎，眼萎缩。
(11)泌尿生殖系统:少见的:尿急，膀胱炎，尿潴留，月经过多，肾盂肾炎，肾结石，子宫纤维化扩大，阴道念珠菌感染，阴道炎；罕见的:蛋白尿，糖尿，血尿，宫血。
4、药物成瘾与依赖性:还没有进行该药滥用成瘾的人体研究。猴以剂量依赖性的方式给药时，在超过人最大推荐用量(mg/m2)的35倍时，突然停药，可产生短暂的戒断症状，此短暂的戒断症状(活动增加，躯体震颤，对人敌对情绪)不能被纳洛酮逆转。

【禁忌】对盐酸替扎尼定及其他组份过敏的病人禁用。

【注意事项】
1、低血压:替扎尼定为α2受体激动剂(与可乐定相似)，可能引起低血压。一项单次给药的临床研究表明，8mg替扎尼定处理组中2/3的病人收缩压或者舒张压下降20%，低血压在给药后1h出现，2-3h达高峰，有时伴有心动过缓，直立位低血压，轻度头痛/头昏，极少数出现晕厥，此低血压效应为剂量依赖性，在单次剂量大于2mg时，开始监测血压。通过调整剂量和在调整剂量前密切注意低血压的症状和体征，明显的低血压可能可以大大下降。另外，当病人从卧位转为站立位时，低血压和体位性低血压的风险就更大。当合用抗高血压药物时更要警惕，不应该与其他的α2受体激动剂合用。在使用时应告知病人，让患者注意。
2、肝功能损害的危险:替扎尼定偶尔可导致肝损害。在设有对照组的临床研究表明，服用替扎尼定的病人将近5%的患者肝功能检测指标升高，比正常上限高3倍(如原基础值升高者则上升2倍多)，而正常对照组仅有0.4%的病人出现类似情况。大多数病例在停药后迅速恢复，没有留下后遗影响的报道。偶尔有症状表现，如恶心，呕吐，食欲减低，黄疸。上市后发现，有3例服用替扎尼定出现肝功能衰竭死亡的报道，1例49岁男性病人，一次6mg，每日三次，服用2周后，出现进行性黄疸和肝大，肝活检显示多中心性坏死，没有嗜酸性细胞浸润，停止用药，病人10天后死于肝昏迷；该患者没有乙型和丙型肝炎的证据，仅使用过奥沙西泮和雷尼替丁，除了替扎尼定，没有其他原因可解释肝的损害。另外2例，同时使用了有损肝功能的药物。1例同时使用卡马西平，替扎尼定4mg/天，治疗2月后产生胆汁瘀积性黄疸，该病人20天后死于肺炎；另1例病人使用了11天的替扎尼定，在发生迅速而致命的肝功能衰竭之前，还使用了2周的丹曲林。因此，在服用替扎尼定的6个月(1，3，6月)以及6个月后根据具体的临床实际情况，应定期检测病人的转氨酶，并且在已有肝损的病人使用该药更要谨慎。
3、镇静作用:通过多剂量设有对照的临床研究表明，48%的病人主述出现此不良事件，其中10%的患者比较严重，而对照组仅有不到1%，并且，镇静效应在调整剂量的第一周后达高峰，在维持给药期基本稳定；单剂量研究发现，该作用存在剂量依赖性，在服用该药后30分钟开始出现，1.5h达高峰，一般持续6h，剂量过大(16mg)有51%的患者6h后仍昏昏欲睡，对照组或者8mg剂量组仅有13%。镇静作用可能干扰病人的日常生活活动。因此，病人应该被告知该药有镇静作用，而某些职业如驾驶员，操作机械的需要集中注意力

【孕妇及哺乳期妇女用药】本品孕妇及哺乳期妇女用药未充分评价，尚不知道该药是否通过乳汁分泌，但由于该药的脂溶性，有可能进入乳汁，故孕妇及哺乳期妇女用药应充分权衡利弊后，方可考虑。

【儿童用药】儿童用药方面的安全性尚未充分评价。

【老年患者用药】本品主要在肾脏进行排泄，所以在很多使肾机能低下的情况，对老年患者，此药可使血药浓度持续升高，故要注意减少用量；本品有降低血压的作用，老年患者用药应慎重。

【药物相互作用】替扎尼定与降压药合用（包括利尿药）偶可引起低血压和心动过缓。酒精或镇静药可以提高本品的镇静作用。

【药物过量】
已有报道1例46岁患有硬化症的男性病人，1次服用100片（4mg/片）替扎尼定后迅速出现昏迷，体检没有发现瞳孔扩大的眼球震颤，病人出现Cheyme-Stokes样呼吸的明显呼吸抑制，通过洗胃和呋噻咪和甘露醇强迫利尿，病人在几小时后苏醒，没有后遗症，实验室检查正常。
有鉴于此，如果发生过量，首先应确保气道的通畅，其次进行呼吸和循环系统的监测。

Brand Name(s): Zanaflex

【原产地英文商品名】ZANAFLEX TABLET 4mg/tab 150tabs/bottle
【原产地英文药品名】TIZANIDINE HCL
【中文参考药品译名】
注：以下产品不同的规格和不同的价格，购买时请以电话咨询为准！
·ZANAFLEX片剂 2毫克/片 150片/瓶
·ZANAFLEX片剂 4毫克/片 150片/瓶
【中文参考药品译名】盐酸替扎尼定
【生产厂家中文参考译名】ACORDA
【生产厂家英文名】ACORDA

-----------------------------------------------------------------------------------
【原产地英文商品名】TIZANIDINE HCL TABLET(ZANAFLEX TABS GENERIC) 4mg/tab 30tabs/bottle
【原产地英文药品名】TIZANIDINE HCL
【中文参考商品译名】
注：以下产品不同的规格和不同的价格，购买时请以电话咨询为准！
·盐酸替扎尼定片剂(ZANAFLEX片剂仿制药) 4毫克/片 30片/瓶
·盐酸替扎尼定片剂(ZANAFLEX片剂仿制药) 4毫克/片 150片/瓶
·盐酸替扎尼定片剂(ZANAFLEX片剂仿制药) 2毫克/片 150片/瓶
【中文参考药品译名】盐酸替扎尼定
【生产厂家中文参考译名】山德士
【生产厂家英文名】SANDOZ

Zanaflex Oral Uses
This medication is used to treat muscle tightness and cramping (spasm) caused by conditions such as multiple sclerosis or spinal injury. Decreasing spasms can reduce pain and improve your ability to move around. Tizanidine is a short-acting muscle relaxant that works by blocking certain nerve signals from the spine to the brain (alpha adrenergic agonist).

How to use Zanaflex Oral
Take this medication by mouth as directed. When you start this medication, your dosage will probably need to be increased slowly by your doctor to reduce side effects, especially dizziness and/or drowsiness. Ask your doctor or pharmacist how to use this medication correctly, and follow all instructions carefully. This medication usually starts to work in 1 to 2 hours and wears off after 6 to 8 hours. Tizanidine can be taken every 6 to 8 hours, but you should not take more than 36 milligrams a day or more than 3 doses in 24 hours. The dosage is based on your medical condition and response to therapy.

Your body will absorb this medication differently depending on whether you take it as a tablet or capsule, whether you take it with food or on an empty stomach, or if you sprinkle the contents of the capsule on food. Be sure to discuss this with your doctor to determine the best way to take your dose, especially when changes to your dose are being considered or if your doctor prescribes a different form of tizanidine (e.g., tablet or capsule).

This medication may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as anxiety, tremor, increased blood pressure, heart rate and muscle tenseness) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Zanaflex Oral Side Effects
Constipation, dry mouth, drowsiness, dizziness, weakness and fatigue may occur. If any of these effects persist or worsen, contact your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fainting, mental/mood changes including seeing things that aren't there, frequent/burning urination, hearing or vision changes such as blurred vision.

Tell your doctor immediately if any of these rare but very serious side effects occur: black stool, slow or irregular heartbeat.

Tizanidine rarely has caused very serious (possibly fatal) liver disease. Tell your doctor immediately if you develop symptoms of liver disease, including persistent nausea, stomach/abdominal pain, dark urine, yellowing eyes/skin.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Zanaflex Oral Precautions
Before taking tizanidine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure or heart disease, kidney disease, liver disease.

This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Avoid alcoholic beverages.

To minimize dizziness, stand up slowly when arising from a sitting or lying position.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness and drowsiness.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug is excreted into human milk. Consult your doctor before breast-feeding.

Zanaflex Oral Interactions
Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: ciprofloxacin, fluvoxamine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting tizanidine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antiarrhythmics (e.g., amiodarone, mexiletine, propafenone, verapamil), birth control pills, blood pressure drugs (e.g., ACE inhibitors such as lisinopril, beta blockers such as propranolol, clonidine, methyldopa, guanabenz, guanfacine), cimetidine, drugs affecting liver enzymes that remove tizanidine from your body (e.g., zileuton, ticlopidine, acyclovir, fluoroquinolone antibiotics such as norfloxacin), "water pills" (e.g., furosemide, thiazides).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., carbamazepine), medicine for sleep (e.g., sedatives), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines such as chlorpromazine, or tricyclics such as amitriptyline), tranquilizers. Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

Do not use non-prescription medications that contain cimetidine for relief of upset stomach or heartburn.

Do not start or stop any medicine without doctor or pharmacist approval.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

Zanaflex Oral Overdose
If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include severe drowsiness, fainting, trouble breathing, and unconsciousness.

NOTES:
Laboratory and/or medical tests (e.g., blood pressure, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Do not share this medication with others.

MISSED DOSE:
If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE:
Store away from light and moisture at room temperature at 77 degrees F (25 degrees C). Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep this and all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.