英文药名: Campral EC(acamprosate calcium)

中文药名: 坎普拉尔（阿坎酸钙缓释片）

生产厂家: 德国 Merck Serono
药品介绍
英 文 名：Acamprosate Calcium
中 文 名：阿坎酸钙
商 品 名：CAMPRAL
研发厂家：Forest Laboratories, Inc
药理毒理
阿坎酸钙的分子结构与神经递质高牛磺酸（ｈｏｍｏｔａｕｒｉｎｅ）相似，是γ－氨基丁酸（ＧＡＢＡ）和牛磺酸的类似物，属于中枢神经系统的神经调节剂。虽然本药作用机制仍不清楚，但临床试验提示本药可能是通过直接抑制ＧＡＢＡ和大脑伏核（Ｎａｃｃ）中的谷氨酸能受体来发挥其药理作用。
药代动力学
阿坎酸钙口服生物利用度为11%。当患者口服本药666mg，每天3次时，可在5天内达到稳态血药浓度。虽然进食可降低阿坎酸钙口服生物利用度，但这种影响没有临床意义。本药不在体内代谢，直接随尿液经肾脏排泄。
适应症
阿坎酸钙（结合社会心理治疗）有助于酒精依赖性患者在酒精解毒之后继续维持戒酒状态。本药在临床上常常与阿片受体部分拮抗剂纳曲酮合用。
用法用量
本药为缓释片剂，规格为333ng。临床有效剂量为666mg，每天3次，进食时服用。建议患者在出现急性酒精戒断症状后立即服用本药，以防病情复发和达到最佳疗效。中度肾功能损害患者应减量至333mg，每天3次。
任何疑问，请遵医嘱！
不良反应
在临床试验中，受试者对本药耐受良好；不良反应情况在大多数情况下与安慰剂相似。本药最常见的不良反应为消化道反应（包括腹泻），发生率为１０％～１７％（安慰剂组为０．７％）。发生率超过１％的不良反应还包括头痛、腹痛、背痛和寒战。其他类型的不良反应还有心悸、晕厥、外周性水肿和体重增加。此外，在参与临床试验的总数为４４６１名受试者中，还发现了３例原因未明的急性肾功能衰竭病例。
禁　忌
严重肾功能损害患者（肌酸酐清除率≤３０ｍｌ／ｍｉｎ）禁用本药。
注意事项
本药不能减轻急性酒精戒断症候群。事实上，所有参与临床试验的受试者在试验过程中都没有继续饮酒，因此，现实生活中那些持续饮酒的酗酒者在应用本药时有可能达不到所预期的治疗效果。中度肾功能损害患者（肌酸酐清除率为３０～５０ｍｌ／ｍｉｎ）应慎用本药。
药物相互作用
欧洲一项研究发现，虽然建议患者在服用本药过程中完全戒酒，但饮酒并不会影响本药的药代动力学。本药不会与苯二氮类卓药物、抗焦虑药、镇静药、安眠药或者非阿片类镇痛药产生相互作用。 阿坎酸钙（Ａｃａｍｐｒｏｓａｔｅ Ｃａｌｃｉｕｍ），即乙酰高牛磺酸钙，是一种用于治疗酒精依赖性的新药，不过，在欧洲本药已有多年的用药历史。阿坎酸钙一般不会产生滥用，长期用药通常不会出现耐受性或依赖性。
应告知患者从家庭、朋友和精神辅导人员处得到社会心理支持的重要性。在服用本药过程中，患者应避免操作重型机械、驾驶或其他任何需要技巧和协调性的行为，因为本药可能暂时性影响这些功能。
包装规格
333mg*84 片（土耳其Merck 生产）
333mg*168 片（德国 Merck Serono）

Campral EC
1. Name of the medicinal product
Campral EC
2. Qualitative and quantitative composition
Each tablet contains acamprosate (I.N.N.) calcium 333.0 mg as the active ingredient. For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Enterocoated tablets.
4. Clinical particulars
4.1 Therapeutic indications
Acamprosate is indicated as therapy to maintain abstinence in alcohol-dependent patients. It should be combined with counselling.
4.2 Posology and method of administration
Posology
Adults within the age range 18-65 years:
- 2 tablets three times daily with meals (2 tablets morning, noon and night) in subjects weighing 60kg or more.
- In subjects weighing less than 60kg, 4 tablets divided into three daily doses with meals (2 tablets in the morning, 1 at noon and 1 at night).
Older people
Acamprosate should not be used in older people
Paediatric population
Acamprosate should not be used in children
The recommended treatment period is one year. Treatment with acamprosate should be initiated as soon as possible after the withdrawal period and should be maintained if the patient relapses.
Acamprosate does not prevent the harmful effects of continuous alcohol abuse. Continued alcohol abuse negates the therapeutic benefit, therefore acamprosate treatment should only be initiated after weaning therapy, once the patient is abstinent from alcohol.
4.3 Contraindications
− Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
− Lactating women (see section 4.6)
− In cases of renal insufficiency (serum creatinine >120 micromol/L)
4.4 Special warnings and precautions for use
The safety and efficacy of Campral has not been established in patients younger than 18 years or older than 65 years. Campral is therefore not recommended for use in these populations.
The safety and efficacy of Campral has not been established in patients with severe liver insufficiency (Childs-Pugh Classification C).
Because the interrelationship between alcohol dependence, depression and suicidality is well-recognised and complex, it is recommended that alcohol-dependent patients, including those treated with acamprosate, be monitored for such symptoms.
Abuse and dependence
Non-clinical studies suggest that acamprosate has little or no abuse potential. No evidence of dependence on acamprosate was found in any clinical study thus demonstrating that acamprosate has no significant dependence potential.
4.5 Interaction with other medicinal products and other forms of interaction
The concomitant intake of alcohol and acamprosate does not affect the pharmacokinetics of either alcohol or acamprosate. Administering acamprosate with food diminishes the bioavailability of the drug compared with its administration in the fasting state.
In clinical trials, acamprosate has been safely administered in combination with antidepressants, anxiolytics, hypnotics and sedatives, and non-opioid analgesics
Pharmacokinetic studies have been completed and show no interaction between acamprosate and diazepam, disulfiram, oxazepam, tetrabamate, meprobamate or imipramine.
There is no information available on the concomitant administration of acamprosate with diuretics.
4.6 Fertility, pregnancy and lactation
Pregnancy
There is no adequate data from the use of Campral in pregnant women. Animal studies do not indicate any evidence of foetotoxicity or tetragenicity. Campral must therefore only be used during pregnancy after a careful benefit/risk assessment, when the patient cannot abstain from drinking alcohol without being treated with acamprosate and when there is consequently a risk of foetotoxicity or teratogenicity due to alcohol.
Breast-feeding
It is known that Campral is excreted in the milk of lactating animals. It is not known whether acamprosate is excreted in human milk. There are no adequate data from the use of acamprosate in infants. Campral must therefore not be used in breastfeeding women.
If a breastfeeding woman cannot abstain from drinking alcohol without being treated with acamprosate, a decision must be made whether to discontinue nursing or to discontinue Campral, taking into account the importance of the medicinal product to the woman.
Fertility
In animal studies, no adverse effects on fertility were observed. Whether or not acamprosate affects the fertility in humans is unknown.
4.7 Effects on ability to drive and use machines
Campral has no influence on the ability to drive and use machines.
4.8 Undesirable effects
According to information collected during clinical trials and spontaneous reports since marketing authorization, the following adverse reactions may occur under treatment with Campral.
The following definitions apply to the frequency terminology used hereafter:
very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000, including isolated cases), frequency not known (cannot be estimated from the available data)
Gastrointestinal disorders:
Very common: Diarrhoea
Common: Abdominal pain, nausea, vomiting, flatulence
Skin and subcutaneous tissue disorders:
Common: Pruritus, maculo-papular rash
Not known: Vesiculo-bullous eruptions
Immune system disorders:
Very rare: Hypersensitivity reactions including urticaria, angio-oedema or anaphylactic reactions.
Reproductive system and breast disorders:
Common: Frigidity or impotence.
Psychiatric disorders:
Common: Decreased libido
Uncommon: Increased libido
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
4.9 Overdose
Acute overdose is usually mild. In the reported cases, the only symptom, which can be reasonably related to overdose is diarrhoea. No case of hypercalcaemia has ever been reported. Treatment of overdose is directed to symptoms.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Acamprosate (calcium acetylhomotaurinate) has a chemical structure similar to that of amino acid neuromediators, such as taurine or gamma-amino-butyric acid (GABA), including an acetylation to permit passage across the blood brain barrier. Acamprosate may act by stimulating GABAergic inhibitory neurotransmission and antagonising excitatory amino-acids, particularly glutamate. Animal experimental studies have demonstrated that acamprosate affects alcohol dependence in rats, decreasing the voluntary intake of alcohol without affecting food and total fluid intake.
5.2 Pharmacokinetic properties
Acamprosate absorption across the gastrointestinal tract is moderate, slow and sustained and varies substantially from person to person. Food reduces the oral absorption of acamprosate. Steady state levels of acamprosate are achieved by the seventh day of dosing. Acamprosate is not protein bound.
Oral absorption shows considerable variability and is usually less than 10% of the ingested drug in the first 24 hours. The drug is excreted in the urine and is not metabolised significantly. There is a linear relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate.
The kinetics of acamprosate are not modified in group A or B of the Child-Pugh classification of impaired liver function, a population which is likely to be part of the target population for acamprosate. This is in accordance with the absence of hepatic metabolism of the drug.
5.3 Preclinical safety data
In the preclinical studies, signs of toxicity are related to the excessive intake of calcium and not to acetylhomotaurine. Disorders of phosphorus/calcium metabolism have been observed including diarrhoea, soft tissue calcification, renal and cardiac lesions. Acamprosate had no mutagenic or carcinogenic effect, nor any teratogenic or adverse effects on the male or female reproductive systems of animals. Detailed in vitro and in vivo research on acamprosate to detect genetic and chromosomal mutations has not produced any evidence of potential genetic toxicity.
6. Pharmaceutical particulars
6.1 List of excipients
Crospovidone (KOLLIDON CL)
Microcrystalline cellulose (AVICEL PH 101)
Magnesium silicate (COMPRESSIL)
Sodium starch glycolate (EXPLOTAB)
Anhydrous colloidal silica (AEROSIL 200)
Magnesium stearate
Anionic copolymer of methacrylic and acrylic acid ethyl ester (EUDRAGIT L30 D)
Talc
Propylene glycol
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions
6.5 Nature and contents of container
Aluminium/PVC sheets of blisters presented in cartons of 168 tablets.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Merck Santé s.a.s
37 rue Saint Romain
69379 Lyon Cedex 08
France
8. Marketing authorisation number(s)
PL 13466/0001
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 18 December 1995
Date of latest renewal: 24 October 2007
10. Date of revision of the text
March 2015
FDA批准治疗酒精中毒的新药Campral（通用名：阿坎酸[acamprosate]） 
7月29日，FDA宣布批准新药Campral（商品名：坎普劳；通用名：阿坎酸[acamprosate]）用于治疗已经停止饮酒后寻求继续戒酒的酒精依赖者（alcohol dependent individuals）。Campral对于在治疗开始时仍频繁饮酒，或滥用除酒精之外的其它物质的患者，可能不具疗效。
Campral是十年来获准的第一个用于治疗酒精滥用（alcohol abuse）的新药。
酒精中毒(alcoholism)，又称酒精依赖（alcohol dependence），是一种疾病。酒精滥用（alcohol misuse）将造成严重后果，在很多情况下，甚至是威胁生命的。大量饮酒增加患某些癌症的风险，特别是肝脏、食管、咽和喉头等部位的癌症。大量饮酒也会引起肝硬化（liver cirrhosis）、免疫系统疾病、脑损害；如果在怀孕期，将对胎儿造成伤害。慢性酒精中毒（chronic alcoholism）一直以来都是一个普遍存在的消耗性疾病，在医疗保健费用（healthcare costs）、工资损失和个人身心痛苦等方面对社会造成巨大负担。
Campral的作用机制尚未完全明了，目前认为它是通过作用于与酒精滥用有关的脑通路。通过包括已放弃酒精摄入的酒精依赖患者（即，已戒酒者[detoxified]）的多重安慰剂对照临床试验，Campral被证明是安全和有效的。鉴于接受阿坎酸治疗的受试者中较大比例被评定为在整个治疗中达到持续性戒酒，证明Campral在维持戒酒（abstinence）（保持使患者不消费酒）中优于安慰剂。Campral没有成瘾性，并且在临床试验中普遍有良好的耐受性。所报告的患者最常见不良事件，包括头痛、腹泻、胃气胀和恶心。
Campral治疗应作为包括心理社会支持在内的综合治疗项目的一部分。