近日，美国食品和药物管理局（FDA）批准Xywav（calcium, magnesium, potassium, and sodium oxybates.中文译名：羟丁酸钙镁钾钠,JZP-258 ）口服溶液，用于治疗7岁及以上发作性睡病（narcolepsy，嗜睡症）患者的猝倒或过度日间嗜睡（EDS）。
发作性睡病（嗜睡症）是一种无法治愈的慢性神经系统疾病，随着时间的推移，疾病负担会对患者的健康产生深远影响。许多患者在得到正确诊断之前可能会经历数年的时间，这对他们的日常生活会产生重大影响。该病是一种终生的疾病，因此有新的选择来帮助治疗EDS和猝倒非常重要。
Xywav（calcium, magnesium, potassium, and sodium oxybates）是一种羟丁酸盐产品，具有一种独特的阳离子组分（钙镁钾钠），与推荐剂量范围6-9克的羟丁酸钠相比，具有相同的羟丁酸浓度，但可减少92%的钠，或约1000-1500mg/夜。虽然Xywav的确切作用机制尚不清楚，但Xywav对猝倒和EDS的治疗作用被认为是通过睡眠时对去甲肾上腺素能和多巴胺能神经元以及丘脑皮质神经元的GABAB作用所介导的。
批准日期：2020年07月22日 公司：Jazz制药
XYWAV（羟丁酸钙镁钾钠[calcium, magnesium, potassium, and sodium oxybates]）口服溶液，CIII
美国初次批准：2002年
警告：中央神经系统（CNS）抑郁症和滥用与滥用。
有关完整的框内警告，请参阅完整的处方信息。
中枢神经系统抑郁症
•XYWAV是一种中枢神经系统抑制剂，使用XYWAV可能会导致呼吸抑制。
滥用与滥用
•XYWAV的活性部分是羟丁酸酯或γ-羟基丁酸酯（GHB）。滥用或滥用非法GHB与CNS不良反应有关，包括癫痫发作，呼吸抑制，意识减退，昏迷和死亡。
XYWAV仅可通过名为XYWAV和XYREM REMS的受限制程序使用。
作用机理
XYWAV是中枢神经系统抑制剂。XYWAV治疗narcolepsyis的确切作用机理未知。XYWAV是羟丁酸钙，羟丁酸镁，羟丁酸钾和羟丁酸钠（γ-羟丁酸）的混合物。γ-羟基丁酸酯（GHB）是神经递质GABA的内源性化合物和代谢产物。假设XYWAV对多发性多巴胺能神经元以及丘脑皮质神经元在睡眠期间的GABA B作用介导了对分解代谢和白天过度嗜睡的治疗作用。
适应症和用途
XYWAV是一种中枢神经系统抑制剂，可用于治疗7岁及以上发作性睡病的患者瘫痪或白天过度嗜睡（EDS）。
剂量和给药
成人患者的剂量
•以每晚4.5g的口服剂量开始，分为两剂。
•滴定剂每周最多可增加1.5克。
•推荐剂量范围：每晚口服6g至9g。
每晚总剂量   就寝时间    2.5至4小时后
每晚4.5g      2.25克       2.25克
每晚6克       3克          3克
每晚7.5克     3.75克       3.75克
每晚9克       4.5克        4.5克
•有些患者在不等剂量的情况下可能获得更好的反应就寝时间和2.5至4小时后。
儿科患者（7岁及以上）的剂量
•建议的起始剂量，滴定方案和最大总夜间剂量基于体重。
重要行政信息
•睡前准备两个剂量；在药房提供的容器中，用大约1/4杯水稀释每个剂量。
•进食后至少2小时服用夜间首剂XYWAV。
•卧床服用，服药后躺下。
对于从Xyrem转换为XYWAV的患者：以与Xyrem相同的剂量和方案开始（克为克）。根据功效和耐受性进行滴定。
肝功能不全患者
推荐的起始剂量是每晚口服原始剂量的一半，分为两个剂量。
剂量形式和强度
口服溶液：0.5g/mL总盐（相当于0.413g/mL的羟丁酸酯）。
禁忌症
•与镇静催眠药或酒精合用。
•琥珀酸半醛脱氢酶缺乏症。
警告和注意事项
•CNS抑郁症：考虑将XYWAV与其他CNS抑制剂同时使用时要格外小心。
•在给药的前6个小时内或首次开始治疗后，警告患者避免需要完全的心理咨询或运动协调的危险活动，直到确定XYWAV不会对患者产生不利影响。
•抑郁和自杀：监测患者的抑郁和自杀倾向。
•困惑/焦虑：监测运动/认知功能受损。
•妄想症：评估梦游的发作次数。
不良反应
在成年人中（≥5％），最常见的不良反应是头痛，恶心，头晕，食欲下降，失眠，腹泻，多汗症，焦虑症和呕吐。
在含羟丁酸钠（活性成分与XYWAV相同）的儿科研究中，最常见的不良反应（≥5％）为遗尿，恶心，头痛，呕吐，体重减轻，食欲下降和头晕。
要报告可疑的不良反应，请致电1-800-520-5568联系JazzPharmaceuticals，Inc.，或致电1-800-FDA-1088与FDA联系，或访问www.fda.gov/Medwatch。
药物相互作用
•与双丙戊酸钠同时使用：建议将XYWAV初始剂量减少至少20％。
在特定人群中的使用
•怀孕：根据动物数据，可能会造成胎儿伤害。
•老年患者：服用XYWAV时监测运动和/或认知功能是否受损。
包装供应/存储和处理方式
供应方式
XYWAV是透明至微乳白色的口服溶液。每张处方包括一瓶XYWAV，并带有压入式瓶转接器，口腔测量装置（塑料注射器）和药物指南。每次XYWAV运送时，药房都会提供两个带有防儿童漏液盖的空容器。
每个琥珀色瓶均含有浓度为0.5g/mL的XYWAV口服溶液，并带有防止儿童进入的瓶盖。
一瓶180mL：NDC 68727-150-01
存储
请将本品放在儿童不能接触的地方。
XYWAV应存储在20°C至25°C（68°F至77°F）之间;在15°C至30°C（59°F至86°F）之间允许的偏移（请参阅USP控制的室温）。
分配在密闭的容器中。
稀释后制备的溶液应在24小时内食用。
处理与处置
XYWAV是《管制物质法》规定的附表III药物。XYWAV应按照州和联邦法规进行处理。将XYWAV放在下水道下是安全的。
提示：本品属[政府]管制药，不供个人，仅供研发单位！
完整说明资料附件：
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212690s000lbl.pdf
U.S. FDA Approval of Xywav(TM)(calcium, magnesium, potassium, and sodium oxybates) Oral Solution for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy
Xywav is the first FDA approved new treatment option indicated for both cataplexy and excessive daytime sleepiness in people living with narcolepsy in more than 15 years Xywav contains 92 percent less sodium per nightly dose than sodium oxybate, a current standard of care for this patient population as designated by the American Academy of Sleep Medicine Guidelines Narcolepsy is a chronic sleep disorder and is associated with an increased preva lence of certain comorbid conditions, including hypertension and cardiovascular disease.
Important Safety Information
WARNING: Taking XYWAV with other central nervous system(CNS)depressants such as medicines used to make you or your child fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol, or street drugs, may cause serious medical problems, including trouble breathing (respiratory depression), low blood pressure(hypotension), changes in alertness(drowsiness), fainting (syncope), and death.
The active ingredient of XYWAVisa form of gamma hydroxybutyrate(GHB).Abuse or misuse of illegal GHB alone or with other drugs that cause changes in alertness (or consciousness) has caused serious side effects. These effects include seizures, trouble breathing(respiratory depression), changes in alertness(drowsiness), coma, and death. Call your doctor right away if you or your child has any of these serious side effects.
Becauseof these risks, you have to go through the XYWAV and XYREMREMS Program to have your or your child's prescription for XYWAV filled.
Do not take XYWAV if you take or your child takes other sleep medicines or sedatives(medicines that cause sleepiness), drinks alcohol, or has a rare problem called succinic semialdehyde dehydrogenase deficiency.Keep XYWAV in a safe place to prevent abuse and misuse. Selling or giving away XYWAV may harm others, and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.
Anyone who takes XYWAV should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane, for at least 6 hours after taking XYWAV. Those activities should not be done until you know how XYWAV affects you or your child.
XYWAV can cause serious side effects, including the following:
Breathingproblems,including slower breathing, trouble breathing, and/or short periods of not breathing while sleeping(sleep apnea).People who already have breathing or lung problems have a higher chance of having breathing problems when they use XYWAV.
Mental health problems, including confusion, seeing or hearing things that are not real (hallucinations), unusual or disturbing thoughts(abnormal thinking), feeling anxious or upset, depression, thoughts of killing yourself or trying to kill yourself, increased tiredness, feelings of guilt or worthlessness, or difficulty concentrating. Tell your doctor if you or your child have or had depression or have tried to harm yourself or themselves. Call your doctor right away if you have or your child has symptoms of mental health problems or a change in weight or appetite.
Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you or your child starts sleepwalking. Your doctor should check you or your child.
The most common side effects of XYWAV in adults include headache, nausea, dizziness, decreased appetite, parasomnia(a sleep disorder that can include abnormal dreams, abnormal rapid eye movement (REM) sleep, sleep paralysis, sleep talking, sleep terror, sleep-related eating disorder, sleep walking, and other abnormal sleep-related events), diarrhea, excessive sweating (hyperhidrosis), anxiety and vomiting
The most common side effects of XYWAV in children include bedwetting, nausea, headache, vomiting, weight decrease, decreased appetite, and dizziness.
XYWAV can cause physical dependence and craving for the medicine when it is not taken as directed.These are not all the possible side effects of XYWAV.
About Narcolepsy
Narcolepsy is a chronic, debilitating neurological disorder characterized by EDS and the inability to regulate sleep-wake cycles normally.
 It affects an estimated one in 2,000 people in the United States, with symptoms typically appearing in childhood or adolescence.
Studies have shown it may take 10 years or more for people with narcolepsy to receive a diagnosis.
There are five main symptoms of narcolepsy, including EDS, cataplexy, disrupted nighttime sleep, sleep-related hallucinations, and sleep paralysis.
While all people with narcolepsy experience EDS, not all individuals with narcolepsy experience all five symptoms.
EDS is the primary symptom of narcolepsy and is present in all people with the disorder.
EDS is characterized by the inability to stay awake and alert during the day resulting in drowsiness and unplanned lapses into sleep.
Narcolepsy is associated with an increased preva lence of cardiometabolic comorbidities, including obesity, hypertension, diabetes and hypercholesterolemia.