药品名称
【通用名】：丙戊酸钠
【商品名】：德巴金
【英文名】：Compound Sodium Valproate and Valproic Acid SR Tablets
【成份】: 丙戊酸钠。
【药品介绍】
FDA批准了缓释片剂Depakote（双丙戊酸钠divalproex sodium）的通用名药，该药已获准用于治疗癫痫、双向情感障碍和偏头痛。 　　
有FDA官员就此表示，对通用名类药物的审批程序及其严格、科学，以保证药物在质量、安全性和疗效等各方面达到其专利药的水平。此次Depakote通用名的获准给患者又增加了一种可选的治疗药。 　　
通用名双丙戊酸钠的用药安全提示将与Depakote相同，其中包括一个特别的警示信息，即使用该药后有可能导致肝脏损害（肝中毒）和胰腺炎，甚至有致命危险。而且，使用这种药物治疗还会增加胎儿出现缺陷的几率，其中包括神经管畸形。 　　
获准产销双丙戊酸钠的企业包括：印度太阳制药公司、加拿大Genpharm、加拿大Nu-Pharm、美国Upsher-Smith、美国TEVA、美国Sandoz、印度Dr. Reddy和印度Lupin。

【药理毒理】
本品系广谱抗癫痫药物，主要作用于中枢神经系统。对动物的药理研究发现本品对各种癫痫的实验模型（全身性和部分性）均有抗惊厥作用。同样本品被发现对人的各种类型癫痫发作有抑制作用。其主要的作用机理可能与增加氨基丁酸的浓度有关。

【药代动力学】
本品口服，其生物利用度接近100％。分布的范围主要限于血液，并迅速交换到细胞外液，脑脊液中的丙戊酸钠的浓度与游离血浆浓度接近。本品能通过胎盘。哺乳期妇女用药时，在乳汁中本品分泌的浓度很低（血清总浓度在1％－10％）。口服后，本品可迅速（3－4天）达到稳态血浆浓度；静脉注射后，几分钟内可达到稳态血浓度，然后可继续静脉滴注维持。本品与血浆蛋白高度结合，与蛋白结合的量呈剂量依赖性，且有饱和现象。丙戊酸分子可以滤出，但仅限游离型（大约10％）。与其它抗癫痫药不同，本品不会增加其降解，也不降解其它药物，如黄体酮，这是由于参与细胞色素P450诱导作用的酶缺乏所致。半衰期约8－20小时，在儿童通常较短。本品通过葡萄糖醛酸化和－氧化代谢，并主要经尿液排泄。

【适应症】
用于治疗全身性及部分发作性癫痫，以及特殊类型的综合症。
全身性癫痫适用于：失神发作、肌阵挛发作、强直阵挛发作、失张力发作及混合型发作。
部分性癫痫适用于：简单部分发作；复杂部分性发作；部分继发全身性发作。特殊类型综合症：West，Lenn0x-Gastaut综合症。

【用法用量】
每日剂量应根据病人年龄及体重来定，而且，应考虑到对丙戊酸的广泛个体敏感性差异。每日剂量、血清浓度和疗效之间相互关系尚未建立。最佳剂量需根据临床反应来确定：当发作不能控制或怀疑有副作用发生时，除临床监测外，要考虑做丙戊酸钠血浆浓度水平的测定，已报导有效范围为40－100mg/l（300－700μm0l/l）。
初始治疗给药方法（口服）：在没有接受其它抗癫痫药的病人，每2－3天间隔增加药物剂量，1周内达到最佳剂量。在以前已接受其它抗癫痫药物的病人，本品要缓慢增加剂量，在2周内达到最佳剂量，其它治疗逐渐减少至停用。如需加用其它抗癫痫药物，应逐渐加入（见药物相互作用）。
推荐用法剂量：最初每日剂量通常为10－50mg/kg，然后剂量调整到最佳剂量（见德巴金初始治疗）。一般剂量为20－30mg/kg，但是，当用此剂量范围不能控制发作时，可进一步增加至足够剂量。如果病人每日用量超过50mg/kg，应对病人仔细监测（见注意事项）。
儿童：通常剂量每日300mg。
成人：通常剂量为20－30mg/kg/d。
老年人：尽管本品的药代动力学有所变化，临床意义不大，但要根据控制发作来决定剂量。
任何疑问，请遵医嘱！

【不良反应】
罕有肝功能损害（见注意事项）致畸胎危险（见妊娠）神经病学障碍：在本品治疗期间，少数患者出现昏睡或木僵，并导致一过性昏迷（脑病），治疗过程中，可单独出现或和癫痫发作同时出现。当剂量减少或停用时，这些症状会减少，这些病例常发现在联合治疗特别是用苯巴比妥或突然增加丙戊酸剂量之后。消化道紊乱（恶心、胃痛）多出现在治疗开始时，但是不需停止治疗，症状通常可在数天内消失。
短暂的和/或与剂量相关的不良反应常有报导：脱发，轻度姿势性震颤和嗜睡。已有报导单纯纤维蛋白原减少或出血时间延长，通常不伴有临床体征，此多发生于大剂量时（丙戊酸钠对血小板聚集第二期有抑制作用）（见妊娠）。
血液系统：多为血小板减少，罕有贫血、白细胞减少或全血细胞减少。偶有胰腺炎的报导，有时导致死亡。有脉管炎的报导无肝功能异常的单纯和轻度高氨血症时有出现，但不需要停止治疗体重增加，闭经及月经紊乱也有报导。偶有报导可逆或不可逆的听力丧失，但其因果关系尚末明确。丙戊酸可引起皮肤反应，如皮疹。在某些病例有毒性上皮坏死溶解，Steven-J0hns0综合征，多形性细斑也有报导。有单独报导，伴随丙戊酸治疗出现可逆性Fanc0ni氏综合征，但其作用机理未明。
【禁忌】
急性肝炎慢性肝炎个人或家族有严重肝炎史，特别是药物所致肝炎对丙戊酸钠过敏者卟啉症。
【注意事项】
肝功能异常发生时情况：极个别有报导严重肝损害甚至死亡。最高危的病人，特别是接受多种癫痫药治疗者，有严重癫痫发作的婴儿和3岁以下的儿童。尤其是那些伴有脑损害，精神迟滞和或遗传代谢或退化性疾病者。3岁以后，发生率明显下降，并随年龄增长而进一步下降。在大多数病例，肝损害在治疗头六个月里出现。
可疑症状：临床症状是早期诊断的依据。特别是黄疸出现之前，出现下列症状应考虑到肝脏功能损害的可能，特别是那些高危病人。
非特异性症状：通常突然出现，如乏力、厌食、嗜睡、思睡，有时伴有反复呕吐和腹痛。癫痫复发。应告诫病人（或患儿家属），当有上述症状出现时，应及时报告医生，并立即进行临床检查及肝功能检查。
观察：在治疗前应进行肝功能检查，在治疗头6个月内也应定期作肝功能监测。在一般检查中，反映蛋白合成的试验，特别是凝血酶原率最为相关。当确定在异常的低凝血酶原率，特别是伴有其它生化异常（纤维蛋白原和凝血因子明显降低，胆红素增加和转氨酶升高）需要停止本品治疗。作为预防措施，如病人同时服用水杨酸盐也应停用，因为这些药物的代谢途径是相同的。在治疗开始之前或手术前和自发性挫伤或出血时应查血常规，血细胞计数，包括血小板计数，出血时间和凝血时间（见不良反应）。在肾功能不全的病人，由于游离血清丙戊酸水平增高，因而需要减少本品的剂量。偶有报导应用德巴金时常出现免疫功能异常，在系统性红班狼疮的病人使用时，需要权衡本品的利弊。偶有胰腺炎报导。因此当服用本品病人患急性腹疼时，应查血清淀粉酶。
【孕妇及哺乳期妇女用药】
妊娠癫痫妇女在妊娠期间接受丙戊酸治疗时伴随出现的危险如下：伴随癫痫和癫痫药出现的危险在接受抗癫痫治疗的母亲所生下的婴儿畸形的总发生率已证明高于一般孕妇（3％）的2－3倍，虽然有报导在多种药物治疗时，婴儿畸形率增高。但是（与畸形有关的）治疗与疾病关系尚未正式确定。最常见的畸形为唇裂和心血管畸形。突然中断抗癫痫药物治疗可能引起母亲病情加重和引起对胎儿的不利作用。伴随本品出现的危险在动物，已证实对小鼠、大鼠及兔有致畸胎作用。在人类，接受本品治疗的妇女。在怀孕期前三个月出现畸形的总危险性并不高于其它抗癫痫药。已有复合畸形报告特别是肢体畸形的病例。那些作用的发生率尚未完全确定。
本品有引起神经管缺损的倾向：脊髓脑膜膨出，脊柱裂鼓等。这些不良反应的发生率估计为1－2％。纵观上述数据如果妇女计划怀孕，要复习抗癫痫治疗的指征，应考虑补充叶酸盐。在妊娠期，丙戊酸抗癫痫治疗如果有效则不应停止，建议单药治疗；应使用每日最小有效剂量，分次服用。应进行特殊的产前检查监测，以检出可能发生的神经管缺损或其它畸形新生儿危险性。有报导妊娠母亲应用丙戊酸钠，新生儿出现出血综合征。此种出血综合征与血纤维蛋白过少有关；已有报告低纤维蛋白血症且可能是致命的。低纤维蛋白血症可能伴随凝血因子减少而出现、这种综合征要与维生素K依赖因子减少鉴别，后者是由苯巴比妥和酶诱导剂诱导所致。哺乳期本品在母乳内分泌量是低的。大约为母亲血清水平的1－10％。至今，新生儿期母乳喂养的婴幼儿尚未发现临床上的副作用。
【药物相互作用】
丙戊酸钠对其他药物的作用神经阻滞剂、单胺氧化酶抑制剂、抗抑郁药和苯并二氮卓类。本品可以增强其它精神系统药物的作用，如上述药。因此应进行临床监测并按需要调整剂量。
苯巴比妥：本品增加苯巴比妥的血浆浓度（由于抑制了肝脏分解代谢）导致镇静作用，尤其是儿童。因此，在联合用药的最初15天内要进行临床监测、如出现镇静情况，应及时减少苯巴比妥的剂量，必要时测定血浆苯巴比妥的水平。
脱氧苯比妥（扑痫酮）：本品增高血浆脱氧苯巴比妥的水平，加重其副作用（如镇静），当长期治疗时，副作用会消失。在联合用药开始时，应进行临床观察，需要时应调整剂量。
苯妥英钠：本品增高苯妥英钠的总血浆浓度，另外本品增加游离苯妥英钠可能引起过量的症状（丙戊酸把苯妥英钠从它的血浆蛋白结合点置换出来，同时减少了苯妥英钠的肝脏分解代谢）。因此，应进行临床监测，当测定血浆苯妥英钠水平后，还应再测定游离苯妥英钠。
卡马西平：本品与卡马西平联合应用时，已有报导其临床毒性即丙戊酸可增加卡马西平的毒性作用。在联合用药开始时，应进行临床观察，需要时应调整剂量。
拉莫三嗪：丙戊酸能减少拉莫三嗪代谢，需要时应调整剂量（减少拉莫三嗪剂量）。
迭氮胸苷：丙戊酸钠可提高血浆迭氮胸苷浓度导致迭氮胸苷毒性的增加。其它药物对本品的影响有酶诱导作用的抗癫痫药（包括苯妥英钠，苯巴比妥，卡马西平），能减低血清丙戊酸浓度。当联合治疗时，应根据血药浓度来调整剂量。FELBAMATE和丙戊酸联合应用时，可增高血清丙戊酸浓度，丙戊酸剂量应予监测。甲氟喹增加丙戊酸代谢并有引起惊厥作用。因此，在联合治疗时可能出现癫痫发作。当本品与对蛋白结合力高的药物（如阿斯匹林）同时应用时，血清游离丙戊酸水平可能增高。当与甲氰咪呱或红霉素同时应用时，血清丙戊酸水平可以增高（由于肝脏代谢等降低的结果）。其它相互作用丙戊酸通常没有酶诱导作用，因此丙戊酸不会减低使用避孕药妇女的雌黄体酮激素的的效果。同时应用维生素K依赖性因素抗凝剂时，应严密监测凝血酶原率。
【药物过量】
服用本品急性过量在临床中的表现为或深或浅的昏迷，伴随有肌张力减退，全身水肿，缩瞳症和呼吸自主性减退等。曾有报导一些病例发生伴有脑水肿的颅内高压。对服药过量的病人医院应采取以下救助措施：消化道排空、并保证有效的排尿和心脏呼吸检测。对非常严重的病人，必要时应对其进行体外透析。尽管曾报导有部分病例死于过量服药，但一般此类中毒反应不至于威胁生命。
【原产地英文商品名】VALPROIC ACID SYRUP(DEPAKOTE GENERIC)250mg/5ml 480mls/bottle
【原产地英文药品名】VALPROATE SODIUM
【中文参考商品译名】
注：以下产品是不同规格和不同的价格，购买时请以电话咨询为准
·双丙戊酸钠SPRINKLE胶囊剂(德巴金SPRINKLES仿制药)125毫克/胶囊 100胶囊/盒
·丙戊酸胶囊剂(德巴金仿制药)250毫克/胶囊 100胶囊/盒
·双丙戊酸钠ER片剂(德巴金ER仿制药)500毫克/片 30片/盒
·双丙戊酸钠ER片剂(德巴金ER仿制药)250毫克/片 30片/盒
·双丙戊酸钠肠溶缓释片(德巴金仿制药)125毫克/片 30片/盒
·丙戊酸糖浆(德巴金仿制药)250毫克/5毫升 480毫升/瓶
【中文参考药品译名】丙戊酸钠

Depakote
Generic Name: divalproex sodium (dye val PRO ex)
Brand Names: Depakote, Depakote ER, Depakote Sprinkles
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What is Depakote?
Depakote affects chemicals in the body that may be involved in causing seizures.
Depakote is used to treat various types of seizure disorders. It is sometimes used together with other seizure medications. It is also used to treat the manic phase of bipolar disorders (manic-depressive illness), and to prevent migraine headaches.
Depakote may also be used for other purposes not listed in this medication guide.
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Important information about Depakote
In rare cases, Depakote has caused life-threatening liver failure, especially in children younger than 2 years old. Children may be at even greater risk for liver problems if they use more than one seizure medication, if they have a metabolic disorder, or if they have a brain disease causing mental impairment (such as Creutzfeldt-Jacob disease, Huntington disease, multiple sclerosis, or a brain injury or infection). Seek emergency medical attention if the person taking this medicine has nausea, vomiting, stomach pain, or loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). These symptoms may be early signs of liver damage. Some of these symptoms may also be early signs of pancreatitis. Depakote can cause birth defects. Do not use this medication without your doctor's consent if you are pregnant. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment.
You may have thoughts about suicide while taking Depakote. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.
Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.
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Before taking Depakote
In rare cases, Depakote has caused life-threatening liver failure, especially in children younger than 2 years old. Children of this age may be at even greater risk for liver problems if they use more than one seizure medication, if they have a metabolic disorder, or if they have a brain disease causing mental impairment (such as Creutzfeldt-Jacob disease, Huntington disease, multiple sclerosis, or a brain injury or infection). Depakote has also caused rare cases of life-threatening pancreatitis (inflammation of the pancreas). Pancreatitis can come on suddenly and symptoms may start even after you have been taking Depakote for several years. Do not take Depakote if you have liver disease or a urea cycle disorder.
If you have any of these other conditions, you may need a dose adjustment or special tests to safely take Depakote.
a bleeding or blood clotting disorder;
a history of head injury, brain disorder, or coma;
a family history of a urea cycle disorder;
a family history of infant deaths with unknown cause; or
HIV or CMV (cytomegalovirus) infection.

You may have thoughts about suicide while taking Depakote. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.
Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.
FDA pregnancy category D. This medication can cause harm to an unborn baby. Do not use Depakote without your doctor's consent if you are pregnant. Tell your doctor if you become pregnant during treatment. Depakote can cause birth defects. Use an effective form of birth control while you are using this medication. Depakote passes into breast milk and could harm a nursing infant. Do not take this medication without telling your doctor if you are breast-feeding a baby.
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How should I take Depakote?
Take Depakote exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor.
Follow the instructions on your prescription label.
Drink plenty of water while you are taking Depakote. Your dose may need to be changed if you do not get enough fluids each day.
To be sure this medication is not causing harmful effects, your liver function will need to be tested. It is important that you not miss any scheduled visits to your doctor.
Do not stop taking Depakote even if you feel better. It is important to take this medication regularly to prevent seizures from recurring. Get your prescription refilled before you run out of medicine completely. Call your doctor promptly if this medicine does not seem to be working as well in preventing your seizures. Do not crush, chew, break, or open a delayed-release or extended-release tablet or capsule. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking or opening the pill would cause too much of the drug to be released at one time.
You may open the Depakote sprinkle capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule.
Carry an ID card or wear a medical alert bracelet stating that you are taking this medication, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are taking Depakote. Store this medication at room temperature away from moisture and heat.
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What happens if I miss a dose?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.
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What happens if I overdose?
Seek emergency medical attention if you think you have used too much of this medicine.
Overdose symptoms may include sleepiness or drowsiness, shallow breathing, weak pulse, or loss of consciousness.
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What should I avoid while taking Depakote?
Avoid drinking alcohol, which can increase some of the side effects of Depakote.
Depakote can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Depakote can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.
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Depakote side effects
Seek emergency medical attention if the person taking Depakote has nausea, vomiting, stomach pain, or loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). These symptoms may be early signs of liver damage. Some of these symptoms may also be early signs of pancreatitis.
Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.
Get emergency medical help if you have any of these signs of an allergic reaction to Depakote: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have any of these serious side effects:
unexplained weakness with vomiting and confusion or fainting;
easy bruising or bleeding, blood in your urine;
fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;
fever, chills, body aches, flu symptoms;
urinating less than usual;
hallucinations (seeing things that aren't there);
extreme drowsiness, lack of coordination; or
double vision or back-and-forth movements of the eyes.

Less serious Depakote side effects may include:
mild drowsiness or weakness;
diarrhea, constipation, upset stomach;
depression, anxiety, or other emotional changes;
changes in your menstrual periods;
enlarged breasts;
tremor (shaking);
hair loss;
weight changes;
vision changes; or
unusual or unpleasant taste in your mouth.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
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What other drugs will affect Depakote?
Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for depression or anxiety can add to sleepiness caused by Depakote. Tell your doctor if you regularly use any of these medicines, or any other seizure medication.
Before taking this medication, tell your doctor if you are using any of the following drugs:
topiramate (Topamax);
tolbutamide (Orinase);
a blood thinner such as warfarin (Coumadin);
aspirin or acetaminophen (Tylenol);
zidovudine (Retrovir);
clozapine (Clozaril, FazaClo);
diazepam (Valium);
meropenem (Merrem);
rifampin (Rifadin, Rimactane, Rifater); or
ethosuximide (Zarontin);
This list is not complete and there may be other drugs that can interact with Depakote. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
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Where can I get more information?
Your pharmacist can provide more information about Depakote.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.