盐酸美金刚口服溶液说明书

 
通用名称：盐酸美金刚口服溶液 
英文名称：Memantine Hydrochloride Oral Solution 

【适应症】 
        治疗中重度至重度阿尔茨海默型痴呆。 

【不良反应】 
        盐酸美金刚口服溶液的不良事件总发生率与安慰剂水平相当，且所发生的不良事件通常为轻中度。盐酸美金刚口服溶液的常见不良反应（发生率低于2%）有幻觉、意识混沌、头晕、头痛和疲倦。少见的不良反应（发生率为0.1-1%）有焦虑、肌张力增高、呕吐、膀胱炎和性欲增加。根据自发报告，有癫痫发作的报告，多发生在有惊厥病史的患者。 

【禁忌】 
        对于癫痫患者、有惊厥病史、或癫痫乙肝体质患者使用美金刚时应慎重。妊娠期不应服用，哺乳期服用应停止哺乳。 

【注意事项】 
        1.肾功能损害患者：对于肾功能轻度损害（血清肌酐水平不超过130 μmol/L）患者，无需调整剂量。对于中度肾功能损害（肌酐清除率40-60 mL/min/1.73 m2）患者，应将盐酸美金刚口服溶液剂量减至每日10 mg。目前尚无盐酸美金刚口服溶液用于严重肾功能损害（肌酐清除率小于9 mL/min/1.73 m2）患者的资料，因此不推荐在这种患者中使用盐酸美金刚口服溶液。 

        2.肝功能损害患者：目前尚无美金刚应用于肝功能损害患者的资料。 

        3.癫痫患者、有惊厥病史、或癫痫易感体质的患者应用美金刚时应慎重。 

        4.尿液pH值升高的患者服用盐酸美金刚口服溶液时必须进行密切监测。 

        5.心肌梗塞、失代偿性充血性心力衰竭和未有效控制的高血压患者应用美金刚的资料有限，因此这些患者服用盐酸美金刚口服溶液时应密切观察。 

        6.中重度至重度阿尔茨海默型痴呆病通常会导致驾驶和机械操作能力的损害，而且盐酸美金刚口服溶液可能改变患者的反应能力，因此服用盐酸美金刚口服溶液的患者在驾车或操作机械时要特别小心。 

【特殊人群用药】 
        妊娠与哺乳期注意事项： 
        妊娠期不应服用，哺乳期服用应停止哺乳。 

【药物相互作用】 
        根据盐酸美金刚口服溶液的药理作用和作用机制，可能有下列相互作用： 

        在合并使用NMDA拮抗剂时，左旋多巴，多巴胺受体激动剂和抗胆碱能药物的作用可能会增强，巴比妥类和神经阻滞剂的作用有可能减弱。美金刚与抗痉挛药物（如丹曲洛林或巴氯芬）合用时可以改变这些药物的作用效果，因此需要进行剂量调整。 

        因为美金刚与金刚烷胺在化学结构上都是NMDA拮抗剂，因此应避免合用，以免发生药物中毒性精神病。同样道理，也不应将美金刚与氯胺酮或右美沙芬合用。在已发表的一个报道中，美金刚与苯妥英合用可能风险增加。 

        由于其它药物（如西咪替丁，雷尼替丁，普鲁卡因酰胺，奎尼丁、奎宁以及尼古丁）与金刚烷胺共用相同的肾脏阳离子转运系统，因此也有可能与美金刚产生相互作用，导致血浆水平升高的潜在风险。 

        美金刚与双氢克尿噻或任何一个含双氢克尿噻的复方制剂合并应用时有可能使双氢克尿噻的血清水平降低。 　 

        美金刚在离体条件下不抑制细胞色素酶(CYP1A2、2A6、2C9、2D6、2E1、3A)、环氧化物水解酶和硫酸化以及含单氧化酶的黄素的活性。 

【药理作用】 
        盐酸美金刚是谷氨酸受体拮抗剂，可以阻断谷氨酸浓度病理性升高导致的神经元损伤，主要用于中重度AD患者。由于作用机制不同，盐酸美金刚可与胆碱酯酶抑制剂合用，增加疗效。越来越多的证据显示谷氨酸能神经递质功能障碍(尤其是NMDA受体功能损害时)会表现出神经退行性痴呆的临床症状和疾病进展。美金刚是一种电压依赖性、中等程度亲和力的非竞争性NMDA受体拮抗剂。它可以阻断谷氨酸浓度病理性升高导致的神经元损伤。 

Ebixa

Active Substance: memantine hydrochloride 
Common Name: memantine 
ATC Code: N06DX01
Marketing Authorisation Holder: H. Lundbeck A/S
Active Substance: memantine hydrochloride 
Status: Authorised
Authorisation Date: 2002-05-15
Therapeutic Area: Alzheimer Disease
Pharmacotherapeutic Group: Other antidementia drugs

Therapeutic Indication

Treatment of patients with moderate to severe Alzheimer's disease.

What is Ebixa?

Ebixa is a medicine that contains the active substance memantine hydrochloride. It is available as tablets (5 mg, 10 mg, 15 mg and 20 mg). Ebixa is also available as an oral solution, which is supplied with a pump that delivers 5 mg memantine hydrochloride with each activation.

What is Ebixa used for?

Ebixa is used to treat patients with moderate to severe Alzheimer’s disease. Alzheimer’s disease is a type of dementia (a brain disorder) that gradually affects memory, intellectual ability and behaviour.

The medicine can only be obtained with a prescription.

How is Ebixa used?

Treatment should be started and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer’s disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Ebixa by the patient.

Ebixa should be given once a day at the same time every day. To prevent side effects, the dose of Ebixa is gradually increased over the first three weeks of treatment: during the first week, the dose is 5 mg; in the second week, it is 10 mg; and during the third week, it is 15 mg. From week four onwards, the recommended maintenance dose is 20 mg once a day. The tolerance and dose should be assessed within three months after starting treatment, and from then on the benefits of continuing treatment with Ebixa should be re-assessed on a regular basis. The dose may need to be reduced in patients who have moderate or severe problems with their kidneys. If the solution is used, the dose should first be pumped onto a spoon or into a glass of water. It should not be poured or pumped directly into the mouth.

For more information, see the package leaflet.

How does Ebixa work?

The active substance in Ebixa, memantine hydrochloride, is an antidementia medicine. The cause of Alzheimer’s disease is unknown, but memory loss in the disease is believed to be due to a disturbance of message signals in the brain.

Memantine works by blocking special types of receptor called N-methyl-D-aspartate (NMDA) receptors, to which the neurotransmitter glutamate normally attaches. Neurotransmitters are chemicals in the nervous system that allow nerve cells to communicate with one another. Changes in the way glutamate transmits signals within the brain have been linked to the memory loss seen in Alzheimer’s disease. In addition, overstimulation of the NMDA receptors may result in cell damage or death. By blocking NMDA receptors, memantine improves the transmission of signals in the brain and reduces the symptoms of Alzheimer’s disease.

How has Ebixa been studied?

Ebixa has been studied in three main studies including a total of 1,125 patients with Alzheimer’s disease, some of whom had taken other medicines for their disease in the past.

The first study involved 252 patients with moderately severe to severe disease, while the other two involved a total of 873 patients with mild to moderate disease. Ebixa was compared with placebo (a dummy treatment) over 24 to 28 weeks. The main measures of effectiveness were the change in symptoms in three main areas: functional (the degree of disability), cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).

Ebixa was also studied in three additional studies including a total of 1,186 patients with mild to severe disease.

What benefit has Ebixa shown during the studies?

Ebixa was more effective than placebo at controlling the symptoms of Alzheimer’s disease. In the study of moderately severe to severe disease, patients taking Ebixa had fewer symptoms than those taking placebo after 28 weeks, as measured on both global and functional scores. In the two studies of mild to moderate disease, patients on Ebixa had less severe symptoms after 24 weeks, as measured on the global and cognitive scores. However, when these results were considered along with those of the three additional studies, it was noted that the effect of Ebixa was smaller in patients with mild disease.

What is the risk associated with Ebixa?

The most common side effects with Ebixa (seen in between 1 and 10 patients in 100) are somnolence (sleepiness), dizziness, hypertension (high blood pressure), dyspnoea (difficulty breathing), constipation, headache and drug hypersensitivity (allergy to the medicine). For the full list of all side effects reported with Ebixa, see the package leaflet.

Ebixa should not be used in people who may be hypersensitive (allergic) to memantine hydrochloride or any of the other ingredients.

Why has Ebixa been approved?

The CHMP decided that Ebixa’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Ebixa

The European Commission granted a marketing authorisation valid throughout the European Union for Ebixa on 15 May 2002.

For more information about treatment with Ebixa, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.