英文药名: Depakene(Valproic Acid Capsules) 中文药名: 丙戊酸胶囊 生产厂家: Abbott 药品名称 【别名】二丙基乙酸钠; 抗癫灵; 乙-丙基戊酸钠, 丙戊酸钠, 敌百痉, 二丙二乙酸钠, α-丙基戊酸钠, 德巴金 【外文名】Sodium Valproate, Depakene, Depakin,Epilim, Leptilan, Labazene, Valproic 药理作用 抗癫痫作用机理尚未阐明，可能与脑内抑制性神经递质γ-氨基丁酸(GABA)的浓度升高有关。一般GABA的升高是通过代谢的降低或重吸收来达到。另外丙戊酸作用于突触后感受器部位模拟或加强着GABA的抑制作用，对神经膜的作用则尚未完全阐明，可能直接作用于对钾传导有关的膜活动。 药动学 口服从胃肠道迅速吸收，胶囊剂与普通片约经1—4小时血药浓度可达峰值，肠溶片则需3—4小时，饭后服用延迟吸收。缓释片在胃内可有少量释放，在肠道亦缓慢吸收，因此达峰时间较长，峰浓度较低，可以避免一天内血药浓度的过大波动，其生物利用度与肠溶片相同。各种剂型的生物利用度近100％。T1／2为7—10小时。有效血药浓度为50—100µg／ml。血浆蛋白结合率高，约80～94％，随着血药浓度的增高，游离部分逐渐增多，从而增加进入脑组织的梯度；尿毒症和肝硬化时则降低。在肝中代谢，包括葡糖醛酸化和某些氧化过程。主要由肾排泄，少量随粪便排出。妊娠早期丙戊酸与血浆蛋白结合可减少到74％。半减期为5～20h。本药与多种抗癫痫药物合用时半减期可缩短。丙戊酸可通过胎盘，并从乳汁中少量分泌。 适应症 用于其它抗癫痫药无效的各型癫痫病人，尤以小发作者最佳。 用法用量 口服：成人每次２００～４００ｍｇ，每日２～３次，儿童每日３０～６０ｍｇ，分次给药。一般宜从小量开始。如原服用其他抗癫痫药者，可合并应用，也可逐渐减少原药量，视情况而定。 任何疑问，请遵医嘱！ 不良反应 最常见副反应是胃肠功能紊乱，其中以丙戊酸半钠的反应最小。如果反应严重时。可将药物与食物同服或逐渐加量或减少剂量。 少见副反应有食欲和体重增力、嗜睡和共济失调、头昏和头痛，造血系统方面有出血时间延长、血小板减少，白细胞减少或骨髓抑制、血小板减性紫癜。少数患者治疗初期时有肝功能损害，甚至高血氨症和Reye综合征。岩有肝功能损害时，应早期停药以免肝昏迷。偶有高血糖症发现和血清锌含量卜降。 妊娠期用丙戊酸盐，胎儿有神经管发育缺陷的危险，脊柱裂发中率为1％，为一般人患此病的20倍。在男性中应用本组药游离睾酮的血浓度降低。本组药也可产生Vonwinebrand病相类似的症状。本药可产生强直和震颤、颈和脊柱张力障碍的锥体外系症状，也有木僵状态伴有脑电图异常。偶有胰腺炎，可在疗程的任何时间产生。有胰腺症状出现时应即停药，以免造成死亡。 少许患者有皮疹、血管炎(皮肤)、暂时性脱发。有烟酸缺乏症的赖皮病表现。 约有1％～7％儿童用药后有夜尿，可能本组药影响睡眠周期之故，减药或停药后好转。 注意事项 (1)本药能透过胎盘屏障，动物试验有致畸的报道，人类尚未能证实。孕妇应用时需权衡利弊得失。 (2)丙戊酸可经乳腺分泌入乳汁，浓度为母体血药浓度的1—10％，哺乳期妇女应予注意。 (3)有肝病或明显肝功能损害时禁用。有血液病、肝病史、肾功能损害、器质性脑病时慎用。 ①于进餐后立即服用，以减少药物对胃部的刺激。 ②用药期间避免饮酒。 ③如拟停药，应逐渐减量，以防再次出现发作；当取代其他抗惊厥药物时，丙戊酸(钠)用量应逐渐增加，而被取代的药物应逐渐减少，以维持对发作的控制。 ④外科手术或其他急症治疗时应考虑可能遇到的出血时间延长或中枢神经抑制药作用的增强。用药前和用药期间应作血细胞包括血小板计数，肝、肾功能检查，肝功能在最初半年内最好每1—2月复查一次，半年后复查间隔酌量延长。 药物相互作用 (1)饮酒可加重镇静作用。 (2)全麻药或中枢神经抑制药与丙成酸合用，前者的临床效应可更明显。 (3)与抗凝药如华法林或肝素等，以及溶血栓药合用，可能增加抗凝药的效应；丙戊酸可引起低凝血酶原症和抑制血小板凝聚作用，给予抗凝药或溶血栓药，出血的危险性增加。 (4)与阿司匹林或双嘧达莫合用，可由于减少血小板凝聚而延长出血时间。 (5)与苯巴比妥类药合用，后者的代谢减慢，血药浓度上升，因而增加镇静作用而导致嗜睡。 (6)与扑米酮合用，也可引起血药浓度升高，导致中毒，必要时需减少扑米酮的用量。 (7)与氯硝西泮合用防治失神发作时，曾有报道少数病例反而诱发失神状态。 (8)与苯妥英合用时，因与蛋白结合的竞争可使两者的血药浓度发生改变，由于苯妥英浓度变化较大，需经常测定，但是否需要调整剂量应视临床情况与血药浓度而定。 (9)与卡马西平合用，由于肝酶的诱导而致药物代谢加速，可使二者的血药浓度和半衰期降低，故需监测血药浓度以决定是否需要调整用量。 (10)与对肝脏有毒性的药物合用时，潜在着肝脏中毒的危险。有肝病史者长期应用需经常检查肝功能。 (11)与氟哌啶醇、洛沙平(loxapine)、马普替林(maprotiline)、单胺氧化酶抑制药、吩噻嗪、噻吨和三环类抗抑郁药合用，可以增加中枢神经系统的抑制，降低惊厥阈和丙戊酸的效应，需及时调整用量以控制发作。 规格 丙戊酸胶囊250mg.500mg; 丙戊酸肠溶胶囊 500mg; 丙戊酸糖浆250mg/5ml X 450ml。 Brand name: Depakene Generic name: Valproic acid Why is Depakene prescribed? Depakene, an epilepsy medicine, is used to treat certain types of seizures and convulsions. It may be prescribed alone or with other anticonvulsant medications. Most important fact about Depakene Depakene can cause serious, even fatal, liver damage, especially during the first 6 months of treatment. Children under 2 years of age are the most vulnerable, especially if they are also taking other anticonvulsant medicines and have certain other disorders such as mental retardation. The risk of liver damage decreases with age; but you should always be alert for the following symptoms: loss of seizure control, weakness, dizziness, drowsiness, a general feeling of ill health, facial swelling, loss of appetite, vomiting, and yellowing of the skin and eyes. If you suspect a liver problem, call your doctor immediately. Note too that Depakene has been known to cause rare cases of life-threatening damage to the pancreas. This problem can develop at any time, even after years of treatment. Call your doctor immediately if any of the following warning signs appear: abdominal pain, loss of appetite, nausea, and vomiting. How should you take Depakene? If Depakene irritates your digestive system, take it with food. To avoid irritating your mouth and throat, swallow Depakene capsules whole; do not chew them. If you miss a dose... If you take 1 dose a day, take the dose you missed as soon as you remember. If you do not remember until the next day, skip the dose you missed and go back to your regular schedule. If you take more than 1 dose a day and you remember the missed dose within 6 hours of the scheduled time, take it immediately. Take the rest of the doses for that day at equally spaced intervals. Never take 2 doses at once. Storage instructions... Store at room temperature. What side effects may occur? Side effects are more likely if you are taking more than one epilepsy medication, and when you are taking higher doses of Depakene. Indigestion, nausea, and vomiting are the most common side effects when you first start taking this drug. If any side effects develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Depakene. Side effects may include: Abdominal cramps, amnesia, breathing difficulty, depression, diarrhea, dimmed or blurred vision, drowsiness, hair loss, indigestion, infection, involuntary eye movements, loss or increase in appetite, nausea, nervousness, ringing in the ears, sleeplessness, swelling of the arms and legs due to fluid retention, throat inflammation, tremors, vomiting Why should Depakene not be prescribed? You should not take this drug if you have liver disease or your liver is not functioning properly, or if you have had an allergic reaction to it. Special warnings about Depakene Remember that liver failure is possible when taking Depakene (see "Most important fact about this drug"). Your doctor should test your liver function at regular intervals. Also keep in mind the threat of damage to the pancreas (see "Most important fact about this drug"). This problem can develop rapidly, so contact your doctor immediately if you experience any symptoms. In people with a rare set of genetic abnormalities called urea cycle disorders, Depakene may adversely effect the brain. Signs of a developing problem include lack of energy, repeated attacks of vomiting, and mental changes. If you suspect a problem, see your doctor immediately. Depakene may have to be discontinued. Depakene has also been known to cause a very rare but potentially fatal skin condition. Contact your doctor if you notice any changes in your skin. Some side effects are more likely if you have manic episodes or suffer from migraines. Your doctor will monitor your care closely if you have one of these conditions. Because of the potential for side effects involving blood disorders, your doctor will probably test your blood before prescribing Depakene and at regular intervals while you are taking it. Bruising, hemorrhaging, or clotting disorders usually mean the dosage should be reduced or the drug should be stopped altogether. Depakene may cause drowsiness, especially in older adults. You should not drive a car, operate heavy machinery, or engage in hazardous activity until you know how you react to the drug. Do not abruptly stop taking this medicine without first consulting your doctor. A gradual reduction in dosage is usually required to prevent major seizures. This drug can also increase the effect of painkillers and anesthetics. Before any surgery or dental procedure, make sure the doctor knows you are taking Depakene. Possible food and drug interactions when taking Depakene If Depakene is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Depakene with the following: Amitriptyline Aspirin Barbiturates such as phenobarbital and secobarbital Blood-thinning drugs such as warfarin Carbamazepine Clonazepam Diazepam Ethosuximide Felbamate Lamotrigine Meropenem for injection Nortriptyline Phenytoin Primidone Rifampin Tolbutamide Zidovudine Extreme drowsiness and other serious effects may occur if Depakene is taken with alcohol or other central nervous system depressants such as alprazolam, temazepam, or triazolam. Special information if you are pregnant or breastfeeding If taken during pregnancy, Depakene may harm the baby. The drug is not recommended for pregnant women unless the benefits of therapy clearly outweigh the risks. In fact, women in their childbearing years should take Depakene only if it has been shown to be essential in the control of seizures. Since Depakene appears in breast milk, nursing mothers should use it only with caution. Recommended dosage for Depakene ADULTS AND CHILDREN 10 OR OLDER The usual starting dose is 10 to 15 milligrams per 2.2 pounds of body weight per day. Your doctor may increase the dose at weekly intervals by 5 to 10 milligrams per 2.2 pounds per day until seizures are controlled or side effects become too severe. If stomach upset develops, the dose may be increased more slowly. The daily dose should not exceed 60 milligrams per 2.2 pounds per day. OLDER ADULTS Older adults generally are prescribed reduced starting doses, and receive dosage increases more gradually than younger people. Overdosage Any medication taken in excess can have serious consequences. An overdose of Depakene can be fatal. If you suspect an overdose, seek medical help immediately. Symptoms of Depakene overdose may include: Coma, extreme drowsiness, heart problems