FDA批准Jazz公司生产的羟丁酸钠口服液（sodium oxybate，Xyrem）用于治疗嗜睡症患者的白天睡眠过多(EDS)。

羟丁酸钠是γ-氨基丁酸（GABA）的的代谢物，γ-羟基丁酸的钠盐，特别用来治疗深眠型障碍，另外，因为有研究显示，纤维肌痛病患一般有深眠障碍，科学家推测此药物可能有助于治疗此状况的症状。

以前的概念验证研究提供的证据认为，相较于安慰剂，羟丁酸钠可以减少疼痛和疲累，也可使纤维肌痛病患睡眠时的多频生理检查侦测有所改善。

目前的第3期随机双盲研究则评估对548名有此状况之病患的治疗。

病患被指派接受每晚4.5克羟丁酸钠，每晚6.0克羟丁酸钠或安慰剂，给药时间为就寝时与之后2.5至4小时，整个疗程为14周。

完成研究的334名病患报告指出，在研究的第一周疼痛就有减少。使用4.5克羟丁酸钠和6.0克羟丁酸钠的病患，疼痛减少30％以上者比安慰剂组多（分别是54.2％与58.5％，安慰剂组为35.2％，P <.001）。

使用羟丁酸钠者中，报告疼痛减少50％以上者也比安慰剂组多（分别是44.7％与43.3％，安慰剂组为22.7％，P小于0.001）。

整个研究期间，相较于安慰剂组，4.5克羟丁酸钠组和6.0克羟丁酸钠组的平均疲累分数也显著降低，研究开始的第一周的P值小于0.01，研究结束时，分别是-27.94与-30.02，安慰剂组为-17.57; P小于0.001。

研究结束时，相较于安慰剂组，4.5克羟丁酸钠组和6.0克羟丁酸钠组报告指出整体评估分数变化为“不错”或“好很多”的百分比也显著较多（分别是48.3％与45.4 ％，安慰剂组为27.2％，P小于0.001）。

最常见的副作用是头痛（4.5克组有15％;6.0克组有23％），恶心（4.5克组有14％;6.0克组有21％），以及头昏眼花（4.5克组有13％ ;6.0克组有17％）。

主要研究者，加州圣巴巴拉，萨姆松诊所的神经科专家维克托罗森菲尔德医师表示，机转和睡眠没有直接关联，美国目前核准的三种纤维肌痛药物 - 度洛西汀与米那普仑普瑞巴林 - 可能不符合此状况的特征。

他表示，事实上，纤维肌痛病患的调查显示，疼痛是最常发生的抱怨的第4名。睡眠问题，疲累，认知功能不佳是此类病患最主要的抱怨，所以我们知道，纤维肌痛不只有疼痛问题而已。

这项研究强调的是如何治疗睡眠问题，藉由目前尚不清楚的机转而有助于减少疼痛。

他表示，该研究不只显示羟丁酸钠治疗可改善病患的睡眠和疲累，更有趣的是，他们的疼痛也有相当程度的改善。

他表示，就减少疼痛的资料看来，这个安眠药物的止痛效果优于目前其他美国FDA核准的纤维肌痛药物。

密西根大学风湿科医学教授丹尼尔J Clauw医师表示，他认为羟丁酸钠代表一个令人振奋的纤维肌痛新疗法，提出其他治疗方法未着眼的，有关于脑部的重要部份。

他表示，这独一无二的药物或许不只因为改善睡眠，因为其他药物，如三环抗忧郁药和加巴喷丁/普瑞巴林，作用也是改善睡眠。更令人振奋的性质是，此药可能可以提高GABA的值，使它因而有独特性，因为其他已经核准或习于用来治疗纤维肌痛的药物，都没有这个作用于神经传导物质的性质，而这个物质是脑中关键的抑制型神经传导物之一。

这个药物的优点之一是，恶心这个副作用的风险比度洛西汀少，但缺点是，因为羟丁酸钠是一个强力中枢神经系统抑制剂，可能会有滥用风险。但是Clauw医师表示，就处置而言，可接受它为治疗纤维肌痛的有用方法。

他表示，我认为，这有助于此药获得核准用于纤维肌痛。多数医师，包括我自己，一开始可能不会处方它，因为它是受严格管制的物质，不过它已经被睡眠症医师处方用于治疗猝睡症，这些医师也可能乐于用它来治疗纤维肌痛，所以，它可以先用来治疗难治型的纤维肌痛。

本研究接受爵士制药公司公司的资金。罗森菲尔德医师报告接受爵士制药公司公司的研究支持。Clauw医师报告担任多家研究纤维肌痛的药厂的顾问。

Xyrem^® (ZĪE-rem) oral solution(sodium oxybate) CIII

It is very important that you carefully read and follow all instructions before using Xyrem. Read this information carefully before you begin treatment. Read the information you get with each refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment or being familiar with the other patient education materials. Your doctor must instruct you about the safe and effective use of Xyrem. If you have any questions about Xyrem, ask your doctor or call the central pharmacy at the toll free number 1‑866‑XYREM88^® (1‑866‑997‑3688). Do not throw away this Medication Guide. You may need to refer to it again later.

What is the most important information I should know about Xyrem?

• Xyrem is a federally controlled substance. This means that if you sell, distribute, or give your Xyrem to anyone else, or if you use your Xyrem for purposes other than what it was prescribed for, you may be punished under federal and state law by jail and fines.
• It is very important to keep Xyrem out of the reach of children and pets. Get emergency medical help right away if a child drinks your Xyrem.
• Xyrem can cause serious side effects including trouble breathing while asleep, confusion, abnormal thinking, depression, and loss of consciousness. Tell your doctor if you have any of these problems while taking Xyrem.
• The active ingredient of Xyrem is gamma-hydroxybutyrate (GHB). GHB is a chemical that has been abused and misused. Abuse and misuse of Xyrem can cause serious medical problems, including seizures, loss of consciousness, coma, and death. Abuse of Xyrem can lead to dependence, craving for the medicine, and severe withdrawal symptoms.
• Xyrem can cause sleep very quickly. Therefore, take Xyrem only at bedtime and while in bed.
• Do not drive a car, operate heavy machinery, or perform any activity that is dangerous or that requires mental alertness for at least 6 hours after taking Xyrem. When you first start taking Xyrem, until you know whether it makes you sleepy the next day, use extreme care while performing these activities.
• You should not drink alcohol or take other medicines that cause sleepiness. You could have serious side effects.
• You can get Xyrem only by prescription. You must get it through the central pharmacy. Before you first receive Xyrem, your doctor or the central pharmacy will confirm that you understand how to use the drug safely and effectively.

What is Xyrem?

Xyrem is a prescription medicine used for the treatment of narcolepsy, to:

• reduce too much daytime sleepiness
• reduce cataplexy (weak or paralyzed muscles) attacks

Who should not take Xyrem?

Do not take Xyrem if you:

• Take other sleep medicines or sedatives (medicines that cause sleepiness)
• Have a rare condition called succinic semialdehyde dehydrogenase deficiency.

Tell your doctor if you:

• have or had depression or tried to harm yourself. You should be watched carefully for new symptoms of depression.
• have liver problems. Your dose may need to be adjusted.
• have sleep apnea, snoring, breathing, or lung problems. You may have a higher chance of serious breathing problems with Xyrem.
• are on a salt-restricted diet, have high blood pressure, heart failure, or kidney problems. Xyrem contains a lot of sodium (salt) and may not be right for you.
• are pregnant or plan to become pregnant. It is not known if Xyrem can harm your unborn baby.
• are breastfeeding. It is not known if Xyrem can pass through your milk. Talk to your doctor about the best way to feed your baby if you take Xyrem.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and supplements. Especially, tell your doctor if you take other medicines to help you sleep (sedatives). Sedatives should not be used with Xyrem.

How should I take Xyrem?

See “Directions for using Xyrem” at the end of this Medication Guide for detailed information about taking Xyrem.

• Take Xyrem exactly as prescribed by your doctor.
• Take Xyrem two times each night or as directed by your doctor. Follow the “Directions for Use” at the end of this Medication Guide and prepare your Xyrem doses before going to bed. Take the first dose at bedtime while in bed. Take your second dose 2 ½ (2.5) to 4 hours after the first dose. You should set an alarm clock to make sure you wake up to take the second dose. If you miss the second dose, skip that dose and do not take Xyrem again until the next night. Never take two Xyrem doses at once.
• Allow at least 2 hours after eating before taking Xyrem. Food will lower the amount of Xyrem that passes into your body.
• In case of accidental overdose, call 911.
• You should see your doctor every 3 months for a check-up while taking Xyrem. Your doctor should check your response to Xyrem treatment, including improvement in your symptoms and if you are having any side effects.

What are the possible side effects with Xyrem?

Xyrem can cause serious side effects, including:

• breathing problems. These can include decreased breathing, trouble breathing and sleep apnea (short periods of no breathing while sleeping). Patients that already have breathing or lung problems have a higher chance for breathing problems with Xyrem.

• mental health problems. Call your doctor right away if you have:
  • confusion
  • psychosis (seeing or hearing things that are not real)
  • abnormal thinking
  • agitation
  • depression
  • thoughts of killing yourself or try to kill yourself

• bedwetting. Call your doctor if you get this side effect. Your doctor should check you.

• sleepwalking. Sleepwalking can cause injuries. Call your doctor if you start sleepwalking. Your doctor should check you.

The most common side effects with Xyrem are nausea, dizziness, and headache, vomiting, sleepiness and bed-wetting. An increase in side effects may happen with higher doses.

These are not the only possible side effects with Xyrem. If you are concerned about any possible side effects with Xyrem, talk with your doctor.

How should I store Xyrem?

• Always store Xyrem in the original bottle in a safe and secure place, out of the reach of children and pets.
• Keep Xyrem at room temperature, between 59° and 86° F.
• When you have completed using a bottle of Xyrem, pour any unused Xyrem down the drain, cross out the label with a marker, and place the empty bottle in the trash.
• Always place your nightly doses of Xyrem safely out of the reach of children and pets.

General advice about Xyrem

Medicines are sometimes prescribed for purposes not mentioned in Medication Guides. Do not use Xyrem for a condition for which it was not prescribed. Do not give Xyrem to other people. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about Xyrem. If you want more information, talk with your doctor. You can ask your doctor for information about Xyrem that is written for health professionals. Also, you can call the central pharmacy at the toll free number 1-866-XYREM88 (1-866-997-3688).

How is my Xyrem prescription filled?

All Xyrem prescriptions are processed by a central, mail order pharmacy. The pharmacy staff provides several important services, including the following:

• Work with your insurance plan to help you get coverage for Xyrem
• Counsel you on the proper use of Xyrem
• Ship Xyrem to you
• Provide answers to your questions about Xyrem at 1‑866‑XYREM88 (1‑866‑997‑3688)

Directions for Using Xyrem

Never leave your Xyrem in a place where children or pets can get to it.

Your Xyrem shipment will contain 1 or more bottles of medicine, 2 dosing cups with child-resistant caps, a liquid measuring device and this medication guide.

Step 1

Remove the Xyrem bottle and the measuring device from the box (See Figure 1).

Step 2

Remove the measuring device from the wrapper (See Figure 2).

Step 3

Remove the bottle cap by pushing down while turning the cap counterclockwise (to the left). (See Figure 3).

After removing the cap, set the bottle upright on a tabletop.

Step 4

While holding the bottle in its upright position, insert the tip of the measuring device into the center opening on top of the bottle and press down firmly (See Figure 4).

Step 5

While holding the bottle and measuring device down with one hand, draw up the prescribed dose with the other hand by pulling on the plunger.

Note: Medicine will not flow into the measuring device unless you keep the bottle in its upright position (See Figure 5).

Step 6

Remove the measuring device from the center opening of the bottle. Empty each Xyrem dose into a dosing cup, then add about 2 ounces of water (60mL, ¼ cup, or 4 tablespoons) to each cup (See Figure 6).

Prepare both doses before bedtime. Place the caps provided on the dosing cups and turn each cap clockwise (to the right) until it clicks and locks into its child-resistant position (See Figure 7).

Recap the Xyrem bottle and store it in a safe and secure place (locked up if needed), out of the reach of children and pets. Rinse out the liquid measuring device with water.

Step 7

Right before going to sleep, place your second dose in a secure location near your bed. Set an alarm to go off 4 hours after your first dose to wake you up for your second dose. If you wake up before the alarm and it has been at least 2 ½ (2.5) hours, turn off your alarm and take your second dose.

Remove the cap from the first dosing cup by pressing down on the child-resistant locking tab (See Figure 8) and turning the cap counterclockwise (to the left).

Drink all of the first dose right before bedtime (See Figure 9).

Step 8

When you wake up 2 ½ (2.5) to 4 hours later, remove the cap from the second dosing cup. While sitting in bed, drink all of the second dose right before lying down to continue sleeping. Recap the second cup.

Rx only

NDC 68727-100-01

Federal law prohibits the transfer of this drug to any person other than the patient for whom it was prescribed.

Distributed By:Jazz Pharmaceuticals, Inc.Palo Alto, CA 94304

For questions of a medical nature or to order Xyrem call the Xyrem Patient Success Program at 1‑866‑XYREM88 (1‑866‑997‑3688).

Protected by US Patent Numbers 6780889, 6472431; additional patents pending.

PSMG-01

Rev 1105

Part No. 002982

This Medication Guide has been approved by the US Food and Drug Administration.