部分中文Exelon胶囊处方资料（仅供参考）

酒石酸卡巴拉汀(RIVASTIGMINE TARTRATE)
药物毒理
阿尔茨海默病的病理改变主要累及前脑基底部发出至大脑皮质和海马的胆碱能神经通路。已知这些通路与注意力、学习能力、记忆力及其它认知过程有关。重酒石酸卡巴拉汀是一种氨基甲酸类，脑选择性乙酰胆碱酯酶抑制剂，通过延缓功能完整的胆碱能神经元对释放乙酰胆碱的降解，而促进胆碱能神经传导。动物实验结果表明，重酒石酸卡巴拉汀能选择性增强脑皮质和海马等部位乙酰胆碱的效应。所以，本品可以改善阿尔茨海默病患者胆碱能介导的认知功能障碍。另外，胆碱酯酶抑制剂可以减慢淀粉样蛋白β-淀粉样前体蛋白(APP)片段的形成。淀粉样斑块是阿尔茨海默病的重酒石酸卡巴拉汀通过与靶酶结合成共价复合物而使后者暂时丧失活性。人体服用3mg后约1.5小时内，脑脊液(CSF)乙酰胆碱酯酶活性下降近40%。药物达到最大抑制作用后，该酶活性恢复至基础水平约需9小时。阿尔茨海默病患者CSF中重酒石酸卡巴拉汀对乙酰胆碱酯酶的抑制作用呈剂量依赖性，最高试验剂量为6mg，每日2次。

药代动力学 　　
1．吸收：重酒石酸卡巴拉汀完全迅速吸收，约1小时达到血浆峰浓度。因其与靶酶相互作用，所以药物增加的生物利用度超过其增加剂量预计值约1.5倍。服用3mg的绝对生物利用度约36%。重酒石酸卡巴拉汀与食物同服可使其吸收tmax延长90分钟，使其Cmax降低，AUC增加近30%。
2．分布：重酒石酸卡巴拉汀与血浆蛋白结合力较弱(约40%)。它容易通过血脑屏障，体表分布容积为1.8~2.7L/kg。
3．代谢：重酒石酸卡巴拉汀主要通过胆碱酯酶介导的水解作用而迅速、广泛地代谢，血浆半衰期约1小时。体外实验结果表明，这种代谢物仅有微弱的胆碱酯酶抑制作用(小于10%)。体外和动物实验结果表明，大部分细胞色素P450同功酶很少参与重酒石酸卡巴拉汀代谢。体内实验亦证实重酒石酸卡巴拉汀不与细胞色素P450存在相互作用。
4．排泄：尿中未发现重酒石酸卡巴拉汀药物原形，其主要以代谢物通过肾脏排泄。同位素14C标记的重酒石酸卡巴拉汀服用24小时内，大部分经肾脏迅速排泄(大于90%)，仅有小于1%的药物经粪便排泄。阿尔茨海默病患者体内未见重酒石酸卡巴拉汀或其代谢物蓄积。
5．老年受试者：尽管老年人重酒石酸卡巴拉汀生物利用度高于年轻健康志愿者，但对50~92岁阿尔茨海默病患者试验后结果表明，其重酒石酸卡巴拉汀生物利用度不随年龄增加而变化。

适应症
治疗轻、中度阿尔茨海默型痴呆，即可疑阿尔茨海默病或阿尔茨海默病。

用法用量
服药方法：每日2次，与早、晚餐同服。
起始剂量：1.5 mg，每日2次。
递增剂量：推荐起始剂量为1.5 mg，每日2次；如患者服用至少4周以后对此剂量耐受良好，可将剂量增至3 mg，每日2次；当患者继续服用至少4周以后对此剂量耐受良好，可逐渐增加剂量至4.5 mg，以至6 mg，每日2次。
倘若治疗中出现副作用(如恶心、呕吐、腹痛或食欲减退等)或体重下降，应将每日剂量减至患者能够耐受的剂量为止。
维持剂量：1.5-6 mg/次，每日2次。获得最佳疗效的患者应维持其最高的、且耐受良好的剂量。
最高推荐剂量：6 mg/次，每日2次。
肾或肝功能减退患者：肾或肝功能减退患者服药不必调整剂量。
任何疑问，请遵医嘱！

不良反应
总体来说，该药可以出现轻至中度的副作用，通常不予处理即可自行消失。副作用发生的频率及程度常随服药剂量的递增而增多或加重。在欧洲、北美、南非、澳大利亚和日本等地区和国家进行II期和III期临床试验时，所报告的副作用发生率总计为5%或略高，但与本品关系不明显。
一般情况异常：意外创伤7%，疲劳7%，虚弱6%。
中枢和周围神经系统异常：眩晕19%，头痛15%，困倦5%。
胃肠系统异常：恶心38%，呕吐23%，腹泻15%，食欲减退11%，消化不良6%。
精神异常：激动8%，失眠8%，精神错乱6%，抑郁5%。
防御机制异常：上呼吸道感染7%，泌尿道感染5%。
另外，下列副作用在服用本品患者中的发生率至少高出给予安慰剂者2%：出汗增多、全身不适、体重下降、震颤。女性患者对恶心、呕吐、食欲减退和体重下降更为敏感。
本品不引起任何实验室检查项目的改变，包括肝功能或心电图，因此不需进行特殊监护。

禁忌
已知对重酒石酸卡巴拉汀、其它氨基甲酸衍生物或剂型成分过敏的患者禁用。

注意事项
本品对心血管系统不产生副作用。同其它拟胆碱药一样，对病窦综合征或伴严重心律失常患者应慎用。胆碱能样刺激作用可引起胃酸分泌增加。尽管无临床研究资料表明本品能明显加重溃疡病患者的症状，但治疗时该类患者应小心用药。有呼吸系统疾病病史或正在发病的患者服用本品治疗后能产生异常临床表现，或使原来症状和体征加重的临床经验不多，但同其它拟胆碱药一样，对这类患者应慎用。急性支气管哮喘患者服用本品的临床经验尚待进一步研究。拟胆碱药可以加重尿道梗阻和痉挛。虽然在治疗中未发现这种病例，但对此类患者应小心服用本品。
孕妇及哺乳期妇女用药

妊娠期：动物实验表明，重酒石酸卡巴拉汀无致畸作用。妊娠时服用本品的安全性迄今未明。该药仅在对胎儿的益处超过危害时才能应用于妊娠妇女。
哺乳期：本品能否从人体乳汁中分泌目前尚不清楚，服用本品的患者应停止哺乳喂养。

儿童用药
不推荐使用。

老年用药
应在医生指导下使用。

药物相互作用
重酒石酸卡巴拉汀主要通过胆碱酯酶水解代谢，多数细胞色素P450的同功酶很少参与其代谢。因此，本品与由这些酶代谢的其它药物间不存在药代动力学的相互作用。对健康志愿者研究发现，本品与地高辛、华法令、安定或氟西汀间无药代动力学相互作用。华法令所致凝血酶原时间延长不受本品影响。地高辛与本品合用后，没有对心脏传导产生不良的影响。在阿尔茨海默氏病联合药物治疗中，如抗酸药、止吐药、抗糖尿病药、作用于中枢的降血压药(β-阻滞剂、钙通道阻滞剂)、影响肌收缩力药、抗心绞痛药、非甾体抗炎药、雌激素、止痛药、安定、抗组胺药等，均未产生本品的药代动力学改变，以及使临床有关的不利因素增加。由于本品具有影响抗胆碱药物活性的药效学作用特点，所以它不应与其它拟胆碱药合用。作为胆碱酯酶抑制剂，本品可以增强肌肉松弛药镇痛时的肌肉松弛效果。

药物过量
症状：多数意外发生用药过量的病例并未表现出任何临床症状或体征，而且几乎所有过量患者仍可继续使用本品。一旦出现症状，包括恶心、呕吐和腹泻，多数情况下不需给予处理。1例患者摄入药量达46 mg后接受保守治疗，24小时内完全恢复正常。
治疗：因重酒石酸卡巴拉汀的血浆半衰期约1小时，乙酰胆碱酯酶抑制作用周期约9小时。故推荐在随后的24小时内对无症状用药过量患者不应继续使用本品。对用药过量且出现严重恶心、呕吐的患者应考虑使用止吐药。必要时对不良反应给予对症治疗。对严重用药过量的患者可使用阿托品。阿托品硫酸盐初始推荐剂量为0.03 mg/kg，静脉注射，随后可根据其临床疗效调整使用剂量。不推荐东莨菪碱作为解毒药使用。

Exelon
(rivastigmine tartrate) Capsules and Oral Solution

DRUG DESCRIPTION
Exelon (rivastigmine tartrate) is a reversible cholinesterase inhibitor and is known chemically as (S)-N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate hydrogen-(2R,3R)-tartrate. Rivastigmine tartrate is commonly referred to in the pharmacological literature as SDZ ENA 713 or ENA 713. It has an empirical formula of C14H22N2O2?C4H6O6 (hydrogen tartrate salt - hta salt) and a molecular weight of 400.43 (hta salt). Rivastigmine tartrate is a white to off-white, fine crystalline powder that is very soluble in water, soluble in ethanol and acetonitrile, slightly soluble in n-octanol and very slightly soluble in ethyl acetate. The distribution coefficient at 37°C in n- octanol/phosphate buffer solution pH 7 is 3.0.

Exelon Capsules contain rivastigmine tartrate, equivalent to 1.5, 3, 4.5 and 6 mg of rivastigmine base for oral administration. Inactive ingredients are hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, and silicon dioxide. Each hard-gelatin capsule contains gelatin, titanium dioxide and red and/or yellow iron oxides.

Exelon Oral Solution is supplied as a solution containing rivastigmine tartrate, equivalent to 2 mg/mL of rivastigmine base for oral administration. Inactive ingredients are citric acid, D&C yellow #10, purified water, sodium benzoate and sodium citrate.
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INDICATIONS
Exelon? (rivastigmine tartrate) is indicated for the treatment of mild to moderate dementia of the Alzheimer's type.

Exelon? (rivastigmine tartrate) is indicated for the treatment of mild to moderate dementia associated with Parkinson's disease.

The dementia of Parkinson's disease is purportedly characterized by impairments in executive function, memory retrieval, and attention, in patients with an established diagnosis of Parkinson's disease. The diagnosis of the dementia of Parkinson's disease, however, can reliably be made in patients in whom a progressive dementia syndrome occurs (without the necessity to document the specific deficits described above) at least 2 years after a diagnosis of Parkinson's disease has been made, and in whom other causes of dementia have been ruled out (see CLINICAL PHARMACOLOGY, Clinical Trial Data).
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DOSAGE AND ADMINISTRATION
Dementia of the Alzheimer's type
The dosage of Exelon? (rivastigmine tartrate) shown to be effective in controlled clinical trials in Alzheimer's Disease is 6-12 mg/day, given as twice-a-day dosing (daily doses of 3 to 6 mg BID). There is evidence from the clinical trials that doses at the higher end of this range may be more beneficial.

The starting dose of Exelon is 1.5 mg twice a day (BID). If this dose is well tolerated, after a minimum of 2 weeks of treatment, the dose may be increased to 3 mg BID. Subsequent increases to 4.5 mg BID and 6 mg BID should be attempted after a minimum of 2 weeks at the previous dose. If adverse effects (e.g., nausea, vomiting, abdominal pain, loss of appetite) cause intolerance during treatment, the patient should be instructed to discontinue treatment for several doses and then restart at the same or next lower dose level. If treatment is interrupted for longer than several days, treatment should be reinitiated with the lowest daily dose and titrated as described above (see WARNINGS). The maximum dose is 6 mg BID (12 mg/day).

Dementia associated with Parkinson's Disease
The dosage of Exelon? shown to be effective in the single controlled clinical trial conducted in dementia associated with Parkinson's Disease is 3 to 12 mg/day, given as twice-a-day dosing (daily doses of 1.5 to 6 mg BID). In that medical condition, the starting dose of Exelon? is 1.5 mg BID; subsequently, the dose may be increased to 3 mg BID and further to 4.5 mg BID and 6 mg BID, based on tolerability, with a minimum of 4 weeks at each dose.

Exelon should be taken with meals in divided doses in the morning and evening.

Recommendations for Administration: Caregivers should be instructed in the correct procedure for administering Exelon Oral Solution. In addition, they should be directed to the Instruction Sheet (included with the product) describing how the solution is to be administered. Caregivers should direct questions about the administration of the solution to either their physician or pharmacist (see PRECAUTIONS: Information for Patients and Caregivers).

Patients should be instructed to remove the oral dosing syringe provided in its protective case, and using the provided syringe, withdraw the prescribed amount of Exelon Oral Solution from the container. Each dose of Exelon Oral Solution may be swallowed directly from the syringe or first mixed with a small glass of water, cold fruit juice or soda. Patients should be instructed to stir and drink the mixture.

Exelon Oral Solution and Exelon Capsules may be interchanged at equal doses.
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HOW SUPPLIED
Exelon? (rivastigmine tartrate) Capsules equivalent to 1.5 mg, 3 mg, 4.5 mg, or 6 mg of rivastigmine base are available as follows:

1.5 mg Capsule - yellow, "Exelon 1,5 mg" is printed in red on the body of the capsule.
Bottles of 60....................................................................NDC 0078-0323-44
Bottles of 500..................................................................NDC 0078-0323-08
Unit Dose (blister pack) Box of 100 (strips of 10)............NDC 0078-0323-06
Unit Dose Blister Card of 30............................................NDC 0078-0323-15

3 mg Capsule - orange, "Exelon 3 mg" is printed in red on the body of the capsule.
Bottles of 60...................................................................NDC 0078-0324-44
Bottles of 500................................................................ NDC 0078-0324- 08
Unit Dose (blister pack) Box of 100 (strips of 10)............NDC 0078-0324-06
Unit Dose Blister Card of 30...................................NDC 0078-0324-15

4.5 mg Capsule - red, "Exelon 4,5 mg" is printed in white on the body of the capsule.
Bottles of 60....................................................................NDC 0078-0325-44
Bottles of 500..................................................................NDC 0078-0325-08
Unit Dose (blister pack) Box of 100 (strips of 10).............NDC 0078-0325-06
Unit Dose Blister Card of 30............................................NDC 0078-0325-15

6 mg Capsule - orange and red, "Exelon 6 mg" is printed in red on the body of the capsule.
Bottles of 60....................................................................NDC 0078-0326-44
Bottles of 500..................................................................NDC 0078-0326- 08
Unit Dose (blister pack) Box of 100 (strips of 10).............NDC 0078-0326-06
Unit Dose Blister Card of 30.............................................NDC 0078-0326-15
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Store in a tight container.

Exelon? (rivastigmine tartrate) Oral Solution is supplied as 120 mL of a clear, yellow solution (2 mg/mL base) in a 4-ounce USP Type III amber glass bottle with a child-resistant 28-mm cap, 0.5-mm foam liner, dip tube and self- aligning plug. The oral solution is packaged with a dispenser set which consists of an assembled oral dosing syringe that allows dispensing a maximum volume of 3 mL corresponding to a 6-mg dose, with a plastic tube container.
Bottles of 120 mL...............................................................NDC 0078-0339-31

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Store in an upright position and protect from freezing.

When Exelon Oral Solution is combined with cold fruit juice or soda, the mixture is stable at room temperature for up to 4 hours.

Exelon? (rivastigmine tartrate) Oral Solution Instructions for Use
1. Remove oral dosing syringe from its protective case. Push down and twist child resistant closure to open bottle.
2. Insert tip of syringe into opening of white stopper.
3. While holding the syringe, pull the plunger up to the level (see markings on side of syringe) that equals the dose prescribed by your doctor.
4. Before removing syringe containing prescribed dose from bottle, push out large bubbles by moving plunger up and down a few times. After the large bubbles are gone, pull the plunger again to the level that equals the dose prescribed by your doctor. Do not worry about a few tiny bubbles. This will not affect your dose in any way.
Remove the syringe from the bottle.
5. You may swallow Exelon Oral Solution directly from the syringe or mix with a small glass of water, cold fruit juice or soda. If mixing with water, juice or soda, be sure to stir completely and to drink the entire mixture. DO NOT MIX WITH OTHER LIQUIDS.
6. After use, wipe outside of syringe with a clean tissue and put it back into its case.
Close bottle using child resistant closure.

Store Exelon Oral Solution at room temperature below 25°C (77°F) in an upright position. Do not place in freezer.
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SIDE EFFECTS
Dementia of the Alzheimer's type
Adverse Events Leading to Discontinuation
The rate of discontinuation due to adverse events in controlled clinical trials of Exelon? (rivastigmine tartrate) was 15% for patients receiving 6-12 mg/day compared to 5% for patients on placebo during forced weekly dose titration. While on a maintenance dose, the rates were 6% for patients on Exelon compared to 4% for those on placebo.

Most Frequent Adverse Clinical Events Seen in Association with the Use of Exelon
The most common adverse events, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by Exelon's cholinergic effects. These include nausea, vomiting, anorexia, dyspepsia, and asthenia.

Gastrointestinal Adverse Reactions
Exelon use is associated with significant nausea, vomiting, and weight loss (see WARNINGS).

Adverse Events Reported in Controlled Trials
Table 2 lists treatment-emergent signs and symptoms that were reported in at least 2% of patients in placebo-controlled trials and for which the rate of occurrence was greater for patients treated with Exelon doses of 6-12 mg/day than for those treated with placebo. The prescriber should be aware that these figures cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis by which to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

In general, adverse reactions were less frequent later in the course of treatment.

No systematic effect of race or age could be determined from the incidence of adverse events in the controlled studies. Nausea, vomiting and weight loss were more frequent in women than men.

Other adverse events observed at a rate of 2% or more on Exelon 6-12 mg/day but at a greater or equal rate on placebo were chest pain, peripheral edema, vertigo, back pain, arthralgia, pain, bone fracture, agitation, nervousness, delusion, paranoid reaction, upper respiratory tract infection, infection (general), coughing, pharyngitis, bronchitis, rash (general), urinary incontinence.

Dementia Associated with Parkinson's disease
Adverse Events leading to discontinuation
The rate of discontinuation due to adverse events in the single controlled trial of Exelon? (rivastigmine tartrate) was 18.2% for patients receiving 3-12 mg/day compared to 11.2% for patients on placebo during the 24 week study.

The most frequent adverse events that led to discontinuation from this study, defined as those occurring in at least 1% of patients receiving Exelon and more frequent than those receiving placebo, were nausea (3.6% Exelon vs. 0.6% placebo), vomiting (1.9% Exelon vs 0.6% placebo), and tremor (1.7% Exelon vs. 0.0% placebo).

Most Frequent Adverse Clinical Events Seen in Association with the Use of Exelon
The most common adverse events, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by Exelon's cholinergic effects. These include nausea, vomiting, tremor, anorexia, and dizziness.

Adverse Events Reported in Controlled Trials
Table 3 lists treatment emergent signs and symptoms that were reported in at least 2% of patients in placebo-controlled trials and for which the rate of occurrence was greater for patients treated with Exelon doses of 3-12 mg/day than for those treated with placebo. The prescriber should be aware that these figures cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis by which to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.
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DRUG INTERACTIONS
Drug-Drug Interactions
Effect of Exelon on the Metabolism of Other Drugs: Rivastigmine is primarily metabolized through hydrolysis by esterases. Minimal metabolism occurs via the major cytochrome P450 isoenzymes. Based on in vitro studies, no pharmacokinetic drug interactions with drugs metabolized by the following isoenzyme systems are expected: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, CYP2C9, CYP2C8, or CYP2C19.

No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam, or fluoxetine in studies in healthy volunteers. The elevation of prothrombin time induced by warfarin is not affected by administration of Exelon.

Effect of Other Drugs on the Metabolism of Exelon: Drugs that induce or inhibit CYP450 metabolism are not expected to alter the metabolism of rivastigmine. Single dose pharmacokinetic studies demonstrated that the metabolism of rivastigmine is not significantly affected by concurrent administration of digoxin, warfarin, diazepam, or fluoxetine.

Population PK analysis with a database of 625 patients showed that the pharmacokinetics of rivastigmine were not influenced by commonly prescribed medications such as antacids (n=77), antihypertensives (n=72), β-blockers (n=42), calcium channel blockers (n=75), antidiabetics (n=21), nonsteroidal antiinflammatory drugs (n=79), estrogens (n=70), salicylate analgesics (n=177), antianginals (n=35), and antihistamines (n=15).

Use with Anticholinergics: Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications.

Use with Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol.
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WARNINGS
Gastrointestinal Adverse Reactions
Exelon? (rivastigmine tartrate) use is associated with significant gastrointestinal adverse reactions, including nausea and vomiting, anorexia, and weight loss. For this reason, patients should always be started at a dose of 1.5 mg BID and titrated to their maintenance dose. If treatment is interrupted for longer than several days, treatment should be reinitiated with the lowest daily dose (see DOSAGE AND ADMINISTRATION) to reduce the possibility of severe vomiting and its potentially serious sequelae (e.g., there has been one post-marketing report of severe vomiting with esophageal rupture following inappropriate reinitiation of treatment with a 4.5-mg dose after 8 weeks of treatment interruption).

Nausea and Vomiting: In the controlled clinical trials, 47% of the patients treated with an Exelon dose in the therapeutic range of 6-12 mg/day (n=1189) developed nausea (compared with 12% in placebo). A total of 31% of Exelon-treated patients developed at least one episode of vomiting (compared with 6% for placebo). The rate of vomiting was higher during the titration phase (24% vs. 3% for placebo) than in the maintenance phase (14% vs. 3% for placebo). The rates were higher in women than men. Five percent of patients discontinued for vomiting, compared to less than 1% for patients on placebo. Vomiting was severe in 2% of Exelon-treated patients and was rated as mild or moderate each in 14% of patients. The rate of nausea was higher during the titration phase (43% vs. 9% for placebo) than in the maintenance phase (17% vs. 4% for placebo).

Weight Loss: In the controlled trials, approximately 26% of women on high doses of Exelon (greater than 9 mg/day) had weight loss equal to or greater than 7% of their baseline weight compared to 6% in the placebo-treated patients. About 18% of the males in the high-dose group experienced a similar degree of weight loss compared to 4% in placebo-treated patients. It is not clear how much of the weight loss was associated with anorexia, nausea, vomiting, and the diarrhea associated with the drug.

Anorexia: In the controlled clinical trials, of the patients treated with an Exelon dose of 6-12 mg/day, 17% developed anorexia compared to 3% of the placebo patients. Neither the time course or the severity of the anorexia is known.

Peptic Ulcers/Gastrointestinal Bleeding: Because of their pharmacological action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal antiinflammatory drugs (NSAIDs). Clinical studies of Exelon have shown no significant increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.

Anesthesia
Exelon as a cholinesterase inhibitor, is likely to exaggerate succinylcholine- type muscle relaxation during anesthesia.

Cardiovascular Conditions
Drugs that increase cholinergic activity may have vagotonic effects on heart rate (e.g., bradycardia). The potential for this action may be particularly important to patients with "sick sinus syndrome" or other supraventricular cardiac conduction conditions. In clinical trials, Exelon was not associated with any increased incidence of cardiovascular adverse events, heart rate or blood pressure changes, or ECG abnormalities. Syncopal episodes have been reported in 3% of patients receiving 6-12 mg/day of Exelon, compared to 2% of placebo patients.

Genitourinary
Although this was not observed in clinical trials of Exelon, drugs that increase cholinergic activity may cause urinary obstruction.

Neurological Conditions
Seizures: Drugs that increase cholinergic activity are believed to have some potential for causing seizures. However, seizure activity also may be a manifestation of Alzheimer's Disease.

Pulmonary Conditions
Like other drugs that increase cholinergic activity, Exelon should be used with care in patients with a history of asthma or obstructive pulmonary disease.
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PRECAUTIONS
Carcinogenesis, Mutagenesis, Impairment of Fertility
In carcinogenicity studies conducted at dose levels up to 1.1 mg- base/kg/day in rats and 1.6 mg-base/kg/day in mice, rivastigmine was not carcinogenic. These dose levels are approximately 0.9 times and 0.7 times the maximum recommended human daily dose of 12 mg/day on a mg/m2 basis.

Rivastigmine was clastogenic in two in vitro assays in the presence, but not the absence, of metabolic activation. It caused structural chromosomal aberrations in V79 Chinese hamster lung cells and both structural and numerical (polyploidy) chromosomal aberrations in human peripheral blood lymphocytes. Rivastigmine was not genotoxic in three in vitro assays: the Ames test, the unscheduled DNA synthesis (UDS) test in rat hepatocytes (a test for induction of DNA repair synthesis), and the HGPRT test in V79 Chinese hamster cells. Rivastigmine was not clastogenic in the in vivo mouse micronucleus test.

Rivastigmine had no effect on fertility or reproductive performance in the rat at dose levels up to 1.1 mg-base/kg/day. This dose is approximately 0.9 times the maximum recommended human daily dose of 12 mg/day on a mg/m2 basis.

Pregnancy
Pregnancy Category B: Reproduction studies conducted in pregnant rats at doses up to 2.3 mg-base/kg/day (approximately 2 times the maximum recommended human dose on a mg/m2 basis) and in pregnant rabbits at doses up to 2.3 mg-base/kg/day (approximately 4 times the maximum recommended human dose on a mg/m2 basis) revealed no evidence of teratogenicity. Studies in rats showed slightly decreased fetal/pup weights, usually at doses causing some maternal toxicity; decreased weights were seen at doses which were several fold lower than the maximum recommended human dose on a mg/m2 basis. There are no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Exelon should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers
It is not known whether rivastigmine is excreted in human breast milk. Exelon has no indication for use in nursing mothers.

Pediatric Use
There are no adequate and well-controlled trials documenting the safety and efficacy of Exelon in any illness occurring in children.
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OVERDOSE
Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug.

As Exelon? (rivastigmine tartrate) has a short plasma half-life of about one hour and a moderate duration of acetylcholinesterase inhibition of 8-10 hours, it is recommended that in cases of asymptomatic overdoses, no further dose of Exelon should be administered for the next 24 hours.

As in any case of overdose, general supportive measures should be utilized. Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions.

Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Atypical responses in blood pressure and heart rate have been reported with other drugs that increase cholinergic activity when co-administered with quaternary anticholinergics such as glycopyrrolate. Due to the short half-life of Exelon, dialysis (hemodialysis, peritoneal dialysis, or hemofiltration) would not be clinically indicated in the event of an overdose.

In overdoses accompanied by severe nausea and vomiting, the use of antiemetics should be considered. In a documented case of a 46-mg overdose with Exelon, the patient experienced vomiting, incontinence, hypertension, psychomotor retardation, and loss of consciousness. The patient fully recovered within 24 hours and conservative management was all that was required for treatment.
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CONTRAINDICATIONS
Exelon? (rivastigmine tartrate) is contraindicated in patients with known hypersensitivity to rivastigmine, other carbamate derivatives or other components of the formulation (see DESCRIPTION).
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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！
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原产地英文商品名:
EXELON 6mg/capsule 30capsules/box
原产地英文药品名:
RIVASTIGMINE TARTRATE
中文参考商品译名:
艾斯能 6毫克/胶囊 30胶囊/盒
中文参考药品译名:
酒石酸卡巴拉汀
生产厂家中文参考译名:
诺华
生产厂家英文名:
NOVARTIS

---------------------------------------------------------
原产地英文商品名:
EXELON 4.5mg/capsule 30capsules/box
原产地英文药品名:
RIVASTIGMINE TARTRATE
中文参考商品译名:
艾斯能 4.5毫克/胶囊 30胶囊/盒
中文参考药品译名:
酒石酸卡巴拉汀
生产厂家中文参考译名:
诺华
生产厂家英文名:
NOVARTIS

---------------------------------------------------------
原产地英文商品名:
EXELON 3mg/capsule 30capsules/box
原产地英文药品名:
RIVASTIGMINE TARTRATE
中文参考商品译名:
艾斯能 3毫克/胶囊 30胶囊/盒
中文参考药品译名:
酒石酸卡巴拉汀
生产厂家中文参考译名:
诺华
生产厂家英文名:
NOVARTIS
该药品相关信息网址1:
http://www.rxlist.com/exelon-drug.htm

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原产地英文商品名:
EXELON 1.5mg/capsule 30capsules/box
原产地英文药品名:
RIVASTIGMINE TARTRATE
中文参考商品译名:
艾斯能 1.5毫克/胶囊 30胶囊/盒
中文参考药品译名:
酒石酸卡巴拉汀
生产厂家中文参考译名:
诺华
生产厂家英文名:
NOVARTIS