英文药名: Aricept ODT(Donepezil Rapidly Disintegrating Tablets)

中文药名: 安理申多奈哌齐口腔崩解片（快速崩解）

生产厂家: Eisai Inc.

药品名称和成分

商品名：安理申
通用名：盐酸多奈哌齐片
成分: 本品主要成分为盐酸多奈哌齐。本药的无活性成分有单水乳糖、玉米淀粉、微晶纤维素、羟丙基纤维素和硬酯酸镁。
药理作用

药效学: 盐酸多奈哌齐为特异的可逆性乙酰胆碱酯酶抑制剂，此酶主要存在于脑部。盐酸多奈哌齐在活体外实验对乙酰胆碱酯酶的抑制作用比对丁酰胆碱酯酶的抑制作用强1252倍，后者主要存在于中枢神经系统以外。临床试验中，阿尔茨海默型痴呆病人一日一次口服本药5 mg或10 mg ，服药后稳态时乙酰胆碱酶活性测定（红细胞膜）分别被抑制63.6%和77.3%。
盐酸多奈哌齐抑制红细胞乙酰胆碱酯酶活性（AChE）的作用与其ADAS-cog量表的变化有关，这个量表是一个检查认知功能某些方面的敏感量表。尚没有对盐酸多奈哌齐改变疾病的原发神经病理过程的潜力进行过研究。
临床前安全资料：广泛的动物试验表明，该药除了有胆碱能神经兴奋的药理作用以外，其它作用很少。在细菌Ames回复突变实验或小鼠体外淋巴瘤正向突变实验中，未发现盐酸多奈哌齐有致畸作用。体外实验中观察到药物有某些致畸作用，但仅在对细胞有明显毒性的浓度，及在临床试验病人稳态浓度3000倍以上的浓度时才有此作用。在小鼠体内微核模型中，盐酸多奈哌齐无致畸作用。在对大鼠和家兔的长期致癌研究中，没有证据表明有致癌的可能。盐酸多奈哌齐对大鼠生殖功能无影响，在大鼠和家兔中无致畸性，但当给妊娠大鼠50倍人用剂量时，对死胎和仔鼠的早期存活有轻微影响。
药代动力学

药动学 吸收 ：口服本药后3-4小时达血浆峰浓度，血浆浓度和药时曲线下面积与剂量成正比。消除半衰期约70小时，所以，多次每日单剂量给药将缓慢达到稳态。治疗开始后3周内达稳态，稳态后，血浆盐酸多奈哌齐浓度和相应的药效学活性在一日中变化很小。饮食对盐酸多奈哌齐的吸收无影响。
分布 ：约95%的盐酸多奈哌齐与人血浆蛋白结合。有活性的代谢产物6-O-desmethyl donepezil的血浆蛋白结合情况尚不清楚。盐酸多奈哌齐在不同组织中的分布尚未明确研究。但是，在健康成年男性志愿者做的放射性质量平衡研究中，给予单剂14C-标记的盐酸多奈哌齐240小时后，仍有28%的标记物未被回收，表明盐酸多奈哌齐和（或）其代谢物在体内存在10天以上。
代谢/排泄 ：盐酸多奈哌齐以原型由尿排泄，或由细胞色素P450系统代谢为多种代谢产物，其中某些尚未确定。服用单剂14C-标记的盐酸多奈哌齐5 mg后，血浆放射性（以服用剂量的百分比表示），主要为盐酸多奈哌齐原型（30%），6-O-desmethyl donepezil（11%，唯一具有盐酸多奈哌齐相似活性的代谢物），denepezil-cis-N-oxide(9%)，5-O-desmethyl donepezil(7%)和5-O-desmethyl donepezi的葡萄糖醛酸结合物(3%)。约见57%的总放射物从尿中回收(有17%是没有转化的多奈哌齐)，14.5%从粪便中回收，提示生物转化和尿排泄为消除的主要途径。尚无证据表明盐酸多奈哌齐和（或）其代谢产物有肝肠循环。血浆中多奈哌齐浓度以半衰期70小时下降。性别、种族和吸烟史对血浆盐酸多奈哌齐浓度的影响在临床上无显著差异。多奈哌齐的药代动力学还没有在健康的老年人或阿尔茨海默病病人中进行过正式的研究，但是，病人的平均血浆浓度与年轻的健康志愿者的数值相近。
适应症

轻度或中度阿尔茨海默型痴呆症状的治疗。
用法用量

成年/老年人 ：初始治疗用量5 mg/天，1日1次于晚上睡前口服。5 mg/天的剂量应至少维持1个月，以评价早期的临床反应，及达到盐酸多奈哌齐稳态血药浓度。用5 mg/天治疗1个月，并做出临床评估后，可以将本药的剂量增加到10 mg/天，1日1次。推荐最大剂量为10 mg，大于10 mg/天的剂量未做过临床试验。停止治疗后，本药的疗效逐渐减退，中止治疗无反跳现象。
肾功能及轻中度肝功能损害受损者 ： 盐酸多奈哌齐的消除不受影响，因此这些病人可使用相似剂量方案。
儿童 ：不推荐将本药用于儿童。
任何疑问，请遵医嘱！
不良反应

最常见的不良反应（发生率≥ (greater than or equal to) 5%，并且是安慰剂组的2倍）为腹泻、肌肉痉挛、乏力、恶心、呕吐和失眠。其它常见的不良反应（发生率≥ (greater than or equal to) 5%并且≥ (greater than or equal to) 安慰剂组）为头痛、疼痛、意外伤害、普通感冒、腹部器官机能紊乱和头晕。晕厥、心动过缓和少见的窦房传导阻滞、房室传导阻滞和癫痫也有报道。几乎没有报道过包括肝炎的肝功能退化。如果出现不能解释的肝功能退化，应当考虑停用本品。有包括幻觉、易激怒和攻击行为的精神紊乱的报告。解决的办法是减量或停止治疗。也有一些关于厌食，胃、十二指肠溃疡和胃肠道出血的报告。可见血肌酸激酶浓度的轻微增高。
禁忌症

对盐酸多奈哌齐、哌啶衍生物或制剂中赋形剂过敏的病人禁用。妊娠妇女禁用。
注意事项

应当由在阿尔茨海默型痴呆的诊断和治疗方面有经验的医师开始并监督本品的治疗。通过公认的标准来诊断，只有当患者有可靠的照料者，并能够经常监控病人服药时才能开始多奈哌齐的治疗。治疗可以一直持续，只要对病人的益处一直存在。每个病人对多奈哌齐的反应是不能被预估的。对于那些严重的阿尔茨海默型痴呆病人，其它类型的痴呆或其它类型的记忆损伤（例如与年龄相关的认知功能退化）病人应用本品的效果还未全面观察。
麻醉 本药为胆碱酯酶抑制剂，麻醉时可能会增强琥珀酰胆碱型药物的肌肉松弛作用。
心血管系统 胆碱酯酶抑制剂因其药理作用可对心率产生迷走样作用（如心动过缓），患有病窦综合征或其它室上性心脏传导疾病患者需尤其注意。曾有晕厥和癫痫发生的报道。需特别注意观察那些患有心脏传导阻滞或长期窦性间隙的病人。
消化系统 对于患溃疡病的危险性增大的病人，如有溃疡病史或合用非甾体抗炎药物的病人应监测其症状。但在本药的临床试验中，与安慰剂相比，消化性溃疡或胃肠道出血的发病率未见增加。泌尿生殖系统 拟胆碱药物可引起膀胱排出受阻，但在本药临床试验中未见此作用。
神经系统 拟胆碱作用可能引起癫痫大发作，但癫痫也可能是阿尔茨海默病的表现之一。呼吸系统 因其拟胆碱作用， 有哮喘史或阻塞性肺疾病史的病人应慎用胆碱酯酶抑制剂。服用本品时，应避免合用其他乙酰胆碱酯酶抑制剂，胆碱能系统的激动或拮抗剂。
对驾驶及机械操作能力的影响 阿尔茨海默型痴呆本身可能会影响驾驶或操作机器的能力。另外，多奈哌齐可以引起乏力、头晕和肌肉痉挛，主要是开始服用药物或增加药物剂量时。应当根据患者的病情决定其能否继续驾驶及操作复杂机器。
孕妇及哺乳期妇女用药

以约80倍人用剂量在妊娠大鼠和50倍人用剂量在家兔中做的致畸实验结果未发现有致畸性。但以50倍人用剂量在妊娠大鼠所做的实验中，从孕17天至产后20天给药，死产轻微增多。产后4天仔鼠存活率轻度下降，但在约15倍人用剂量的下一个低剂量时，未发现异常作用。多奈哌齐不应在孕期使用。还不清楚盐酸多奈哌齐是否通过妇女乳汁分泌，未在哺乳期妇女中做过试验。因此，服用多奈哌齐的妇女不能哺乳。
药物相互作用

应用多奈哌齐的临床经验目前有限，因为这个原因，可能还没有记录到所有可能出现的相互作用，所以可能会发生新的、未知的与多奈哌齐的相互作用。
盐酸多奈哌齐和（或）其任一代谢产物都不抑制茶碱、华法令、西米替丁或地高辛在人体内的代谢。盐酸多奈哌齐的代谢不被同时服用地高辛或西米替丁所影响。
活体外试验显示，细胞色素酶P450系统的同功酶3A4和很小限度参与的同功酶2D6与多奈哌齐的代谢有关。活体外的药物间相互作用研究显示，酮康唑和奎宁丁，分别是CYP3A4和2D6的抑制剂，抑制多奈哌齐的代谢。因此，这些药物和其它CYP3A4的抑制剂，如伊曲康唑和红霉素，以及CYP2D6的抑制剂，如氟西汀能够抑制多奈哌齐的代谢。在对健康志愿者进行的研究中，酮康唑增加多奈哌齐的平均浓度大约30%。酶的诱导剂，如利福平、苯妥英钠、卡马西平和酒精可能降低多奈哌齐的浓度。因为抑制或者诱导作用的程度还不知道，类似药物的联合应用应当非常谨慎。
盐酸多奈哌齐有与抗胆碱能药物相互作用的可能，也有与共同治疗的药物，如琥珀酰胆碱、其它神经-肌肉阻滞剂、胆碱能激动剂或β-受体阻滞剂（其影响心肌的传导）等有协同作用的可能。
 
药物过量

小鼠及大鼠一次口服单剂盐酸多奈哌齐的半数致死量分别为45和32 mg/kg，或分别为推荐的人用最大剂量10 mg/天的225和160倍。在动物中观察到的与剂量相关的胆碱能兴奋症状包括 ：自发运动减弱、俯卧位、蹒跚步态、流泪、阵挛状惊厥、呼吸抑制、流涎、缩瞳、肌束震颠及体表温度降低。
过量使用胆碱酯酶抑制剂会引起胆碱能危象，表现为严重的恶心、呕吐、流涎、出汗、心动过缓、低血压、呼吸抑制、虚脱和惊厥，可能会有进行性肌无力，如累及呼吸肌可致死。
治疗用药过量的病人，应使用一般支持疗法，给予叔胺型抗胆碱药如阿托品作解毒剂。建议根据反应使用静脉给予的硫酸阿托品，首剂静脉给1 mg和2 mg，然后根据临床表现给药。有报道合用其它拟胆碱药，如与季胺型抗胆碱药格隆溴胺（Glycopyrrolate）合用时，血压和心率反应不典型，尚不清楚盐酸多奈哌齐和（或）其代谢物能否由透析清除（血液透析、腹膜透析或血液过滤）。

包装规格：

·10mg *28快速崩解片
·10mg *84 快速崩解片
·5mg *28 快速崩解片

ARICEPT ODT-donepezil hydrochloride tablet, orally disintegrating 
Eisai Inc.
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HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed to use ARICEPT safely and effectively. See full prescribing information for ARICEPT Tablets and ARICEPT Orally Disintegrating Tablets (ODT).
ARICEPT® (donepezil hydrochloride) tablets
Initial U.S. Approval: 1996
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RECENT MAJOR CHANGES
Addition of new dosage strength: ARICEPT 23 mg
INDICATIONS AND USAGE
ARICEPT is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease (1.0).
DOSAGE AND ADMINISTRATION
Mild to Moderate Alzheimer's Disease - 5 mg or 10 mg administered once daily (2.1)
Moderate to Severe Alzheimer's Disease - 10 mg or 23 mg administered once daily (2.2)
A dose of 10 mg once daily can be administered once patients have been on a daily dose of 5 mg for 4 to 6 weeks. A dose of 23 mg once daily can be administered once patients have been on a dose of 10 mg once daily for at least 3 months (2.3).
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg, 10 mg and 23 mg (3)
Orally Disintegrating Tablets (ODT): 5 mg and 10 mg (3)
CONTRAINDICATIONS
Patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives (4)
WARNINGS AND PRECAUTIONS
Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia (5.1).
Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block (5.2).
ARICEPT can cause vomiting. Patients should be observed closely at initiation of treatment and after dose increases (5.3).
Patients should be monitored closely for symptoms of active or occult gastrointestinal (GI) bleeding, especially those at increased risk for developing ulcers (5.4).
The use of ARICEPT in a dose of 23 mg once daily is associated with weight loss (5.5).
Cholinomimetics may cause bladder outflow obstructions (5.6).
Cholinomimetics are believed to have some potential to cause generalized convulsions (5.7).
Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease (5.8).
ADVERSE REACTIONS
The most common adverse reactions in clinical studies of ARICEPT are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia (6.1).
DRUG INTERACTIONS
Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications (7.3).
A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists (7.4).
USE IN SPECIFIC POPULATIONS
Based on animal data, ARICEPT may cause fetal harm (8.1).
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 
Revised: 11/2010 
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What is Aricept ODT (Donepezil)?
Donepezil improves the function of nerve cells in the brain. It works by preventing the breakdown of a chemical called acetylcholine (ah see til KO leen). People with dementia usually have lower levels of this chemical, which is important for the processes of memory, thinking, and reasoning.
Donepezil is used to treat mild to moderate dementia caused by Alzheimer’s disease.
Donepezil may also be used for other purposes not listed in this medication guide.
What is the most important information I should know about Aricept ODT (Donepezil)?
Before taking donepezil, tell your doctor if you have a heart rhythm disorder such as “sick sinus syndrome” (slow heartbeats), an enlarged prostate, urination problems, asthma, obstructive pulmonary disease, or a seizure disorder such as epilepsy.
If you need to have any type of surgery, tell the surgeon ahead of time that you are taking donepezil.
Donepezil can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.
What should I discuss with my healthcare provider before taking Aricept ODT (Donepezil)?
Do not take this medication if you are allergic to donepezil.
Before taking donepezil, tell your doctor if you are allergic to any drugs, or if you have:
a heart rhythm disorder such as “sick sinus syndrome” (slow heartbeats)
a history of stomach ulcers an enlarged prostate or urination problems
epilepsy or other seizure disorder; or asthma or chronic obstructive pulmonary disease (COPD)
If you have any of these conditions, you may need a dose adjustment or special tests to safely take donepezil.
FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.
It is not known whether donepezil passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.
Aricept ODT Side Effects
What are the possible side effects of Aricept ODT (Donepezil)?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop using donepezil and call your doctor at once if you have any of these serious side effects:
black, bloody, or tarry stools
coughing up blood or vomit that looks like blood or coffee grounds painful or difficult urination
seizure (black-out or convulsions)
Less serious side effects may include:
nausea, vomiting, diarrhea
loss of appetite
muscle cramps
tired feeling; or
sleep problems (insomnia)
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Aricept ODT Interactions
What other drugs affect Aricept ODT (Donepezil)?
Before taking donepezil, tell your doctor if you are taking any of the following medicines:
atropine (Donnatal, and others)
belladonna
carbamazepine (Tegretol)
clidinium (Quarzan)
dexamethasone (Decadron)
dicyclomine (Bentyl)
glycopyrrolate (Robinul)
hyoscyamine (Anaspaz, Cystospaz, Levsin, and others)
mepenzolate (Cantil)
methantheline (Provocholine)
methscopolamine (Pamine), scopolamine (Transderm-Scop)
phenobarbital (Luminal, Solfoton)
phenytoin (Dilantin)
propantheline (Pro-Banthine)
quinidine (Cardioquin, Quinidex, Quinaglute, others)
rifampin (Rifadin, Rifamate, Rifater)
a fungal antibiotic such as ketoconazole (Nizoral), fluconazole (Diflucan), or itraconazole (Sporanox); or aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), diflunisal (Dolobid), etodolac (Lodine), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis), ketorolac (Toradol), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), piroxicam (Feldene), and others This list is not complete and there may be other drugs that can interact with donepezil. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
What should I avoid while taking Aricept ODT (Donepezil)?
Donepezil can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.
Aricept ODT Dosage
How should I take Aricept ODT (Donepezil)?
Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
If you need to have any type of surgery, tell the surgeon ahead of time that you are taking donepezil. You may need to stop using the medicine for a short time.
Donepezil can be taken with or without food or milk.
Take the donepezil regular tablets with a full glass of water.
To take donepezil orally disintegrating tablet (Aricept ODT):
Keep the tablet in its blister pack until you are ready to take the medicine. Open the package and peel or cut the backing from the tablet blister. Do not push a tablet through the backing or you may damage the tablet Using dry hands, remove the tablet and place it in your mouth. It will begin to dissolve right away
Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing Swallow several times as the tablet dissolves. After the tablet dissolves completely, drink a glass of water Donepezil is usually taken at bedtime. Follow your doctor’s instructions.
Store donepezil at room temperature away from moisture and heat.
What happens if I overdose on Aricept ODT (Donepezil)?
Seek emergency medical attention if you think you have used too much of this medicine.
Overdose symptoms may include severe nausea, vomiting, drooling, sweating, blurred vision, feeling light-headed, slow heartbeat, shallow breathing, muscle weakness, fainting, or seizure (convulsions).
What happens if I miss a dose of Aricept ODT (Donepezil)?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.