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盐酸多奈哌齐含片（Donepezil Hydrochloride OD film）

2014-05-08 11:01:23 作者：新特药房来源：互联网浏览次数：154 文字大小：【大】【中】【小】

简介： 英文药名：Donepezil Hydrochloride OD film 中文药名：盐酸多奈哌齐含片生产厂家：日本救急薬品药品介绍药理作用本药是多奈哌齐的盐酸盐，为第二代胆碱酯酶抑制药，是一种长效的阿尔茨海默病(AD ...

关键字：盐酸多奈哌齐含片 Donepezil Hydrochloride OD film 轻至中度认知障碍的阿尔茨海默病

英文药名：Donepezil Hydrochloride OD film

中文药名：盐酸多奈哌齐含片

生产厂家：日本救急薬品
药品介绍
药理作用
本药是多奈哌齐的盐酸盐，为第二代胆碱酯酶抑制药，是一种长效的阿尔茨海默病(AD)的对症治疗药物。近30年的研究表明：AD胆碱能神经元的进行性蜕变是记忆力减退、定向力丧失、行为和个性改变的原因，这种胆碱能理论已被组织学研究证实。本药作用机制是可逆性地抑制乙酰胆碱酯酶(AchE)，使乙酰胆碱水解减少，增加受体部位的乙酰胆碱含量。可能还有其他机制，包括对肽的作用、对神经递质受体或Ca2＋通道的直接作用。
药动学
口服后吸收良好，相对生物利用度为100%，达峰时间为3～4h。每天口服1～10mg，血药浓度与剂量呈线性相关。在多剂量服药后，血浆中浓度蓄积4～7倍，在连服14天后达到稳态。进食和服药时间均不影响药物的吸收程度。血浆蛋白结合率为96%，血药浓度达稳态时分布容积为12L/kg。药物基本上以代谢产物形式从尿中排出，部分代谢产物仍具有胆碱酯酶抑制活性。以14C标记的药物动力学研究表明，服药后10天内，57%从尿中排出，15%从粪便排出，但有28%仍未排出。此后可发现约17%以原药形式从尿中排出。半衰期约为70h，平均血浆清除率为每小时0.13L/kg。
适应证
适用于轻至中度认知障碍的阿尔茨海默病的治疗。
禁忌证
1.对本药或哌啶衍生物高度敏感的患者；
2.哺乳期妇女。
注意事项
1.慎用：
(1)胃肠道疾病活动期或有溃疡病史的患者；
(2)接受非甾体类抗炎药治疗的患者；
(3)哮喘或阻塞性肺病患者；
(4)病窦综合征或室上性心脏传导阻滞患者(本药可能引起心动过缓)；
(5)有癫痫发作史者；
(6)外科大手术患者(多奈哌齐可以增加氯琥珀胆碱型肌肉的松弛)；
(7)妊娠妇女。
2.过量会引起胆碱能危象，重者危及生命，当出现明显中毒反应时静推阿托品1～2mg。
不良反应
最常见的是腹泻、恶心和失眠，通常是轻微和短暂的，无需停药，在1～2天内可缓解。
用法用量
口服给药：每次5mg或10mg，每天1次，睡前服用。3～6个月为一个疗程。
药物相应作用
1.与拟胆碱药(如氨甲酰甲基胆碱)和其他胆碱酯酶抑制药有协同作用。
2.酮康唑、伊曲康唑、奎尼丁可抑制本药代谢，升高其血药浓度。
3.与氯琥珀胆碱类肌松药、抗胆碱药有拮抗作用，故不能合用。
4.苯妥英、苯巴比妥、卡马西平、地塞米松、利福平等药物，可增加本药的清除率，降低本药的血药浓度。5.与洋地黄、华法林联用时，要注意调节剂量。
专家点评
本品为第二代胆碱酯酶抑制剂。抑制乙酰胆碱酯酶活性的强度是抑制丁酰胆碱酯酶的570倍，具有较高的选择性。而且只对脑内胆碱酯酶产生抑制作用，因此是一种长效的阿尔茨海默病(AD)的对症治疗药物。
Donepezil Hydrochloride OD film 3mg 「EE」
Original release：Elmed Eisai co.,ltd.（Prescription drug）
Dosage form：Film・light yellowish white
Active ingredient：Donepezil Hydrochloride
Net weight：1sheet×14packs（14sheets）
Donepezil Hydrochloride OD film 5mg 「EE」
Original release：Elmed Eisai co.,ltd.（Prescription drug）
Dosage form：Film・white
Active ingredient：Donepezil Hydrochloride
Net weight：1sheet×14packs×4（56sheets）
Donepezil Hydrochloride OD film 10mg 「EE」
Original release：Elmed Eisai co.,ltd.（Prescription drug）
Dosage form：Film・pink
Active ingredient：Donepezil Hydrochloride
Net weight：1sheet×14packs×4（56sheets）
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Donepezil Hydrochloride (Tablet, Film Coated)
Description: Donepezil hydrochloride is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (��)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020. Donepezil hydrochloride is a white powder and is freely soluble in water, soluble in chloroform, sparingly soluble in glacial acetic acid and in ethanol, slightly soluble in acetonitrile, very slightly soluble in ethyl acetate and insoluble in n-hexane. CHNOHCl M.W. 415.96 Donepezil hydrochloride is available for oral administration in film-coated tablets containing 5 or 10 mg of donepezil hydrochloride. Inactive ingredients are hypromellose, lactose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol-part. hydrolyzed, pregelatinized starch, talc, and titanium dioxide. Additionally, 10 mg tablets contain iron oxide yellow.
Indication:
Donepezil hydrochloride tablets are indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild to moderate Alzheimer's Disease.
Contraindication:
Donepezil hydrochloride tablets are contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.
Non-proprietary / generic name: Donepezil Hydrochloride
Adverse Outcome:
Mild to Moderate Alzheimer's Disease:
Adverse Events Leading to Discontinuation: The rates of discontinuation from controlled clinical trials of donepezil hydrochloride due to adverse events for the donepezil hydrochloride 5 mg/day treatment groups were comparable to those of placebo-treatment groups at approximately 5%. The rate of discontinuation of patients who received 7 day escalations from 5 mg/day to 10 mg/day, was higher at 13%. The most common adverse events leading to discontinuation, defined as those occurring in at least 2% of patients and at twice the incidence seen in placebo patients, are shown in Table 1.
Most Frequent Adverse Clinical Events Seen in Association with the Use of Donepezil Hydrochloride: The most common adverse events, defined as those occurring at a frequency of at least 5% in patients receiving 10 mg/day and twice the placebo rate, are largely predicted by donepezil hydrochloride's cholinomimetic effects. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia. These adverse events were often of mild intensity and transient, resolving during continued donepezil hydrochloride treatment without the need for dose modification. There is evidence to suggest that the frequency of these common adverse events may be affected by the rate of titration. An open-label study was conducted with 269 patients who received placebo in the 15 and 30 week studies. These patients were titrated to a dose of 10 mg/day over a 6 week period. The rates of common adverse events were lower than those seen in patients titrated to 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day. See Table 2 for a comparison of the most common adverse events following one and six week titration regimens.
Adverse Events Reported in Controlled Trials: The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. Table 3 lists treatment emergent signs and symptoms that were reported in at least 2% of patients in placebo-controlled trials who received donepezil hydrochloride and for which the rate of occurrence was greater for donepezil hydrochloride assigned than placebo assigned patients. In general, adverse events occurred more frequently in female patients and with advancing age.
Other Adverse Events Observed During Clinical Trials: Donepezil hydrochloride has been administered to over 1700 individuals during clinical trials worldwide. Approximately 1200 of these patients have been treated for at least 3 months and more than 1000 patients have been treated for at least 6 months. Controlled and uncontrolled trials in the United States included approximately 900 patients. In regards to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months and 116 patients treated for over 1 year. The range of patient exposure is from 1 to 1214 days. Treatment emergent signs and symptoms that occurred during 3 controlled clinical trials and two open-label trials in the United States were recorded as adverse events by the clinical investigators using terminology of their own choosing. To provide an overall estimate of the proportion of individuals having similar types of events, the events were grouped into a smaller number of standardized categories using a modified COSTART dictionary and event frequencies were calculated across all studies. These categories are used in the listing below. The frequencies represent the proportion of 900 patients from these trials who experienced that event while receiving donepezil hydrochloride. All adverse events occurring at least twice are included, except for those already listed in Tables 2 or 3, COSTART terms too general to be informative, or events less likely to be drug caused. Events are classified by body system and listed using the following definitions: frequent adverse events - those occurring in at least 1/100 patients; infrequent adverse events - those occurring in 1/100 to 1/1000 patients. These adverse events are not necessarily related to donepezilhydrochloride treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies. No important additional adverse events were seen in studies conducted outside the United States. Body as a Whole:Frequent: influenza, chest pain, toothache; Infrequent: fever, edema face, periorbital edema, hernia hiatal, abscess, cellulitis, chills, generalized coldness, head fullness, listlessness. Cardiovascular System:Frequent: hypertension, vasodilation, atrial fibrillation, hot flashes, hypotension; Infrequent: angina pectoris, postural hypotension, myocardial infarction, AV block (first degree), congestive heart failure, arteritis, bradycardia, peripheral vascular disease, supraventricular tachycardia, deep vein thrombosis. Digestive System:Frequent: fecal incontinence, gastrointestinal bleeding, bloating, epigastric pain; Infrequent: eructation, gingivitis, increased appetite, flatulence, periodontal abscess, cholelithiasis, diverticulitis, drooling, dry mouth, fever sore, gastritis, irritable colon, tongue edema, epigastric distress, gastroenteritis, increased transaminases, hemorrhoids, ileus, increased thirst, jaundice, melena, polydipsia, duodenal ulcer, stomach ulcer. Endocrine System:Infrequent: diabetes mellitus, goiter. Hemic and Lymphatic System:Infrequent: anemia, thrombocythemia, thrombocytopenia, eosinophilia, erythrocytopenia. Metabolic and Nutritional Disorders:Frequent: dehydration; Infrequent: gout, hypokalemia, increased creatine kinase, hyperglycemia, weight increase, increased lactate dehydrogenase. Musculoskeletal System:Frequent: bone fracture; Infrequent: muscle weakness, muscle fasciculation. Nervous System:Frequent: delusions, tremor, irritability, paresthesia, aggression, vertigo, ataxia, increased libido, restlessness, abnormal crying, nervousness, aphasia; Infrequent: cerebrovascular accident, intracranial hemorrhage, transient ischemic attack, emotional lability, neuralgia, coldness (localized), muscle spasm, dysphoria, gait abnormality, hypertonia, hypokinesia, neurodermatitis, numbness (localized), paranoia, dysarthria, dysphasia, hostility, decreased libido, melancholia, emotional withdrawal, nystagmus, pacing. Respiratory System:Frequent: dyspnea, sore throat, bronchitis; Infrequent: epistaxis, post nasal drip, pneumonia, hyperventilation, pulmonary congestion, wheezing, hypoxia, pharyngitis, pleurisy, pulmonary collapse, sleep apnea, snoring. Skin and Appendages:Frequent: pruritus, diaphoresis, urticaria; Infrequent: dermatitis, erythema, skin discoloration, hyperkeratosis, alopecia, fungal dermatitis, herpes zoster, hirsutism, skin striae, night sweats, skin ulcer. Special Senses:Frequent: cataract, eye irritation, vision blurred; Infrequent: dry eyes, glaucoma, earache, tinnitus, blepharitis, decreased hearing, retinal hemorrhage, otitis externa, otitis media, bad taste, conjunctival hemorrhage, ear buzzing, motion sickness, spots before eyes. Urogenital System:Frequent: urinary incontinence, nocturia; Infrequent: dysuria, hematuria, urinary urgency, metrorrhagia, cystitis, enuresis, prostate hypertrophy, pyelonephritis, inability to empty bladder, breast fibroadenosis, fibrocystic breast, mastitis, pyuria, renal failure, vaginitis.
Postintroduction Reports: Voluntary reports of adverse events temporally associated with donepezil hydrochloride that have been received since market introduction that are not listed above, and that there is inadequate data to determine the causal relationship with the drug include the following: abdominal pain, agitation, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, and rash.
ドネペジル塩酸塩ODフィルム3mg/5mg/10mg「EE」
单位容量：
3mg
14枚（1枚×14）