苯基丁酸钠片说明书

药品英文名
Sodium Phenylbutyrate
药品别名
苯基丁酸钠、Ammonaps、Buphenyl
药物剂型
片剂：500mg
药理作用
本药为乙酸苯酯的前体药物，主要用于尿素循环障碍的附加治疗。通过调整饮食中氮摄入量及使用本类药物以排泄体内的废氮产物，可以减少尿素循环障碍患者的尿素合成。其具体作用机制如下：本药在体内经β-氧化代谢成乙酸苯酯，乙酸苯酯继而与谷氨酰氨共轭生成苯乙酰谷氨酰氨，上述2步反应均较快而完全。苯乙酰谷氨酰氨作为尿素的替代废氮产物，可通过肾脏排泄，与尿素在摩尔水平上相比，两者每摩尔均含有2摩尔氮(即1摩尔本药也可以清除2摩尔氨基酸来源的氮)。据报道，使用本药治疗尿素循环障碍患者(联合控制饮食氮摄入量)，血氨及血谷氨酸水平可有降低甚至达正常水平。
药动学
本药片剂及粉剂口服后达峰时间分别为1.35h及1h，静脉注射达峰时间为30～60min。女性的苯丁酸及乙酸苯酯的血药浓度峰值及曲线下面积(AUC)高于男性(高30%～50%)，苯乙酰谷氨酰胺药动学未见明显性别差异。表观分布容积为0.2L/kg。主要经肝脏及肾脏迅速代谢为乙酸苯酯及苯乙酰谷氨酰氨。绝大部分药物可在24h内以苯乙酰谷氨酰氨的形式从尿中排泄，少量以药物本体及乙酸苯酯形式排泄(少于口服剂量的1%)。总体清除率为18mg/(kg·h)，母体化合物的消除半衰期为0.8h，乙酸苯酯的消除半衰期为1.2h。
适应证
用于尿素循环障碍的治疗。
禁忌证
1.对本药或乙酸苯酯过敏者。
2.禁用于急性高氨血症的紧急处理。
3.重度高血压、心力衰竭、肾功能不全者。
注意事项
1.本药片剂或粉剂应在进餐时服用，配方粉剂应与食物(固体或液体)混匀服用，并避免与酸性饮料同服。本药自身无臭，但经体内代谢的产物可引起身体异味，影响本药服药依从性(尤其是成人患者)。本药片剂适用于成人及体重20kg以上儿童。配方粉剂可用于口服、经胃造瘘术后、鼻饲。本药应为终身服用，除非通过肝移植进行治疗。
2.慎用：
(1)轻、中度高血压、心力衰竭、肾功能不全者或其他与钠潴留有关的水肿状态。(2)肝功能不全者。
(3)肥胖患者。
3.药物对儿童的影响：有报道儿童服用本药可产生无法预知的不良反应；儿童用药，其自身严重症状及脑损伤仍可能继续加剧。
4.药物对妊娠的影响：国内尚无孕妇用药相关资料，美国药品和食品管理局(FDA)对本药的妊娠安全性分级为C级。
5.药物对哺乳的影响：哺乳妇女用药研究尚不充分，应权衡利弊后用药。
6.用药前后及用药时应当检查或监测：
(1)常规应监测血清蛋白及血浆中氨、谷氨酸、精氨酸水平。
(2)必要时应监测肝肾功、血清白蛋白、总蛋白、动脉血气分析、血电解质浓度，白细胞分类及计数，血小板计数、尿液分析。
7. 贮法：避光，室温保存。
不良反应
常见呼吸频率改变、情绪变化、肌肉疼痛或痉挛、恶心、呕吐、神经过敏或烦躁、踝部及外周水肿等。
国外不良反应参考：
1.心血管系统：可致踝部及外周水肿，血压改变较少见，罕见心律失常及昏厥。2.精神神经系统：可致头痛及抑郁。
3.代谢/内分泌系统：可引起低白蛋白血症(约10%)、代谢性酸中毒(14%)、碱中毒(7%)、高氯血症(7%)，也可致高尿酸血症、低钾血症、低磷血症、高磷血症、高钠血症(发生率低于6%)。
4.泌尿生殖系统：常引起女性月经周期不规则，甚至停经(发生率约23%)。罕见本药引起肾小管酸中毒。
5.肝脏：可引起血清氨基转移酶、胆红素、碱性磷酸酶水平升高，尚无本药致肝毒性的报道。
6.胃肠道：常见食欲缺乏(约4%)，还可引起味觉不佳、腹痛、恶心、呕吐、胃炎，罕见本药引起消化性溃疡、直肠出血、便秘、胰腺炎。
7.血液：可能引起贫血(包括再生障碍性贫血)、白细胞减少或增多、血小板减少，罕见本药引起血小板增多。
8.皮肤：偶有皮疹。
9.其他：本药服用后，可能引起身体异味。
用法用量
成人常规剂量：口服给药：通常每日给药4～6次，进餐时服用，每日给药总量低于20g。一天给药总量超过20g的安全性及有效性尚未确定。儿童常规剂量：口服给药：体重小于20kg儿童，一天450～600mg/kg，分4～6次给药，进餐时服用，每天给药总量低于20g。推荐服用苯丁酸钠粉，不推荐服用苯丁酸钠片。体重大于20kg者，用量同成人。国外用法用量参考：成人常规剂量：口服给药：一天9.9～13g/m2，一天总量超过20g的安全性及有效性尚未确定。肝功能不全时剂量：有实验表明，未患尿素循环障碍的肝功能不全者，本药的代谢及排泄不受影响，尚无资料建议肝功能不全者需调整剂量，但有待进一步研究。儿童常规剂量：口服给药：体重小于20kg儿童，一天450～600mg/kg；体重大于20k者，用量同成人。
药物相应作用
1.与氟哌啶醇、丙戊酸盐、皮质类固醇类药物合用，可能导致高氨血症，合用时应谨慎。
2.与丙磺舒合用可影响苯丁酸盐代谢产物的肾脏排泄，合用时应谨慎。

What is Pheburane and what is it used for?

Pheburane is a medicine that contains the active substance sodium phenylbutyrate. It is used to treat patients who have urea-cycle disorders. These patients are not able to get rid of waste nitrogen from the body because they lack some enzymes that are usually found in the liver. In the body, waste nitrogen is in the form of ammonia, which is toxic when it accumulates, especially for the brain. Pheburane is used in patients who lack one or more of the following enzymes: carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase. It can be used in patients with the following forms of the disease:

· 'early-onset' disease in patients who show a complete lack of one or more of these enzymes within the first month of life;

· 'late-onset' disease in patients who show a partial lack of one or more of these enzymes after the age of one month and have had high blood ammonia levels that affected the brain’s activity.

Pheburane is a ‘hybrid medicine’. This means that it is similar to a ‘reference medicine’ containing the same active substance, but Pheburane granules are available at a lower strength and contain different excipients (inactive ingredients) to mask the unpleasant taste of the active substance. The reference medicine for Pheburane is Ammonaps.

How is Pheburane used?

Pheburane is available as granules (483 mg/g). It can only be obtained with a prescription and treatment should be supervised by a doctor who has experience in treating patients with urea-cycle disorders.

Pheburane is used with a special low-protein diet to reduce the intake of nitrogen. The daily dose of Pheburane is adjusted for each patient individually and depends on the patient’s diet, height and weight. Regular blood tests are needed to find the correct daily dose.

The daily dose of Pheburane should be divided into equal amounts and given with each meal. The granules can be sprinkled onto food immediately before being swallowed or placed in the mouth and swallowed immediately with a drink.

Pheburane may be a life-long treatment unless the patient has a successful liver transplant.

How does Pheburane work?

Eating protein brings nitrogen into the body, which is then transformed into ammonia. Patients with urea-cycle disorders cannot get rid of ammonia from the body, so it can reach high levels, leading to serious problems including disability, brain damage and death. The active substance in Pheburane, sodium phenylbutyrate, is converted into a substance called phenylacetate in the body. Phenylacetate combines with the amino acid glutamine, which contains nitrogen, to form a substance that can be removed from the body by the kidneys. This allows the levels of nitrogen in the body to decrease, reducing the amount of ammonia produced.

How has Pheburane been studied?

Studies in patients have been limited to tests to determine that Pheburane is bioequivalent to the reference medicine, Ammonaps. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Pheburane?

Because Pheburane is a hybrid medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine’s.

Why is Pheburane approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that Pheburane has been shown to have comparable quality and to be bioequivalent to Ammonaps. Therefore, the CHMP’s view was that, as for Ammonaps, the benefit outweighs the identified risk. The Committee recommended that Pheburane be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Pheburane?

Safety information has been included in the summary of product characteristics and the package leafletfor Pheburane, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Pheburane

The European Commission granted a marketing authorisation valid throughout the European Union for Pheburane on 31 July 2013.

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