The Xyrem Patient Success Program^Ò includes detailed information about the safe and proper use of sodium oxybate, as well as information to help the patient prevent accidental use or abuse of sodium oxybate by others. Patients must read and/or understand the materials before initiating therapy. Prescribers will discuss dosing (including the procedure for preparing the dose to be administered) prior to the initiation of treatment. Patients should also be informed that they should be seen by the prescriber frequently during the course of their treatment to review dose titration, symptom response and adverse reactions. Food significantly decreases the bioavailability of sodium oxybate (see Pharmacokinetics). Whether sodium oxybate is taken in the fed or fasted state may affect both the efficacy and safety of sodium oxybate for a given patient. Patients should be made aware of this and try to take the first dose several hours after a meal. Patients should be informed that sodium oxybate is associated with urinary and, less frequently, fecal incontinence. As a safety precaution, patients should be instructed to lie down and sleep after each dose of sodium oxybate, and not to take sodium oxybate at any time other than at night, immediately before bedtime and again 2.5 to 4 hours later. Patients should be instructed that they should not take alcohol or other sedative hypnotics with sodium oxybate.

For additional information, patients should see the Medication Guide for Xyrem.

MEDICATION GUIDE

Xyrem^Ò (Z E-rem) oral solution
(sodium oxybate)
C III

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^Ò (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 knownif 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 ²Directions for using Xyrem² 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 ²Directions for Use² 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).

Figure 1

Step 2

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

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.

Figure 3

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).

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).

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 (60 mL, ¼ cup, or 4 tablespoons) to each cup (See Figure 6).

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.

Figure 7

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).

Figure 8

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

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.

XYREM^Ò RISK MANAGEMENT PROGRAM

I. AS A CONDITION OF APPROVAL, THE REQUIREMENTS OF YOUR RISK MANAGEMENT PROGRAM INCLUDE THE FOLLOWING, WITH THE DETAILS OF THE PROGRAM SET OUT BELOW IN III.

· Implementation of a restricted distribution program for Xyrem
· Implementation of a program to educate physicians and patients about the risks and benefits of Xyrem, including support via ongoing contact with patients and a toll-free Helpline
· Filling of the initial prescription only after the prescriber has received and read the educational materials
· Upon receipt of the initial prescription, the pharmacy will verify that patient education and materials have been provided by the physician. If not, the pharmacy will provide verbal education and supply patient education material with the first prescription.
· Maintain patient and prescribing physician registries

II. YOU HAVE ALSO AGREED TO THE FOLLOWING:

· The bulk drug will be manufactured only at FDA-approved site(s).
· The drug product will be manufactured only at FDA-approved site(s).
· Following manufacture the drug product will be stored at facilities compliant with Schedule III regulations, where a consignment inventory will be maintained.
· Xyrem will be distributed and dispensed through a central pharmacy contracted to fulfill this function. There may also be a designated back-up distributor. Xyrem will NOT be stocked in retail pharmacy outlets.

III. RISK MANAGEMENT PROGRAM DETAILS

A. Dispensing

You will ensure that Xyrem is dispensed in the following manner:

· Prescriptions will be communicated by facsimile or other convenient method by the physician, or the physicians office, to the central pharmacy.
· Upon receipt of a prescription the central pharmacy will contact the prescribing physician and/or the physicians office and
· Identify physicians name, and DEA and state license numbers
· Verify the prescription
· Obtain patient insurance information
· The central pharmacy will then verify that the physician is eligible to prescribe Xyrem by validation of DEA registration via an appropriate database, including confirmation that the physician has an active DEA number, and determine whether any actions are pending against the physician.
· The central pharmacy will ship the Xyrem Physician Success Program^Ò materials to first time prescribers when needed.
· If a patient has prescription drug coverage, the central pharmacy will then contact the patients insurance company to determine coverage, and will notify the patient of his/her approval status.
· All patient registry information will be verified before the initial prescription can be filled.
· Comprehensive printed and video materials (see Xyrem Patient Success Program^Ò
below) that contain information regarding the proper handling of the drug with an outline of precautions to be taken against diversion will be provided to the patient either in advance of or with the first shipment.
· Prior to an initial Xyrem shipment to a patient, the central pharmacy will do one of the following:
· Confirm with the patient by telephone that the patient has read the educational materials contained in the Xyrem Patient Success Program. That confirmation will be recorded by the central pharmacy; or
· Review the educational materials with the patient by telephone to complete the required education. Education over the phone will be documented by the central pharmacy.
· Once approval has been established, the central pharmacy will verify the patients home address and availability for shipping, and arrange shipment through Federal Express or a similar carrier.
· The patient may provide the name of a designee to the central pharmacy who is authorized to accept shipment of Xyrem when the patient is unable to do so. This designee must be 18 years of age or older.
· Receipt of the initial drug shipment will be ensured through the couriers own tracking service for shipments. If the courier tracking service were to indicate a discrepancy from either the patients or designees name, the pharmacy will contact the patient directly by phone to ensure delivery
· The package will be sent under condition that if the patient or his/her designee is unavailable to accept a shipment of Xyrem and execute the required receipt after two delivery attempts, the package will be returned to the pharmacy.
· If a shipment is lost, an investigation will be launched to find it.
· The product may be shipped by the central pharmacy to another pharmacy for patient pickup. The sponsor anticipates that this will be an unusual occurrence, and has a mechanism for verifying the second pharmacys ability to protect against diversion of sodium oxybate before shipping the drug.
· Prescription refills will be permitted in the number specified in the original prescription. In addition, you have agreed that:
· If a prescription refill is requested by the patient prior to the anticipated due date, such refills will be questioned by the pharmacist.
· A lost, stolen, destroyed, or spilled prescription/supply will be documented and the prescription replaced to the extent necessary to honor the original prescription (e.g., a destroyed or spilled bottle will reduce the prescription refill amount). The pharmacist has the discretion to grant or not grant refill requests under those circumstances and at a minimum will contact the prescribing physician to determine if the physician has any special concerns in regard to that refill request. New supplies of Xyrem will be sent to the patient only if the pharmacist and physician are in agreement.
· Repeat instances of lost, stolen, destroyed, or spilled prescriptions/supplies will be flagged for monitoring and future instances thoroughly questioned.
· The first prescription shipment will be limited to a one months supply of Xyrem.
· Following further contact between the pharmacy and patient, and verification that the patient understands the material in the Xyrem Patient Success Program, supplies of Xyrem that are intended to last longer than a month may be shipped.
· The quantity of drug shipped to the patient with each refill may also be regulated based on the requirements of the patients health insurance plan and the terms of the prescription itself.
· It is anticipated that the majority of patients will receive only one months shipment at a time.
· Patients will never receive more than 3 months supply of Xyrem per shipment.
· Physicians are urged to rewrite prescriptions for Xyrem at least every 3 months

B. Registries

· Every patient and prescribing physician will be registered with the central pharmacy in a secure database. The database will contain the physicians name, address, telephone and facsimile numbers, DEA and state license numbers and prescribing frequency. The database will be made available for review by federal and state agencies upon request. From this database it will be possible to obtain the following information:
· Prescriptions by patient name
· Prescriptions by volume (frequency)
· Prescriptions by dose

C. Drug Product Shipments to Patients

Every prescription of Xyrem shipped to the patient will contain all the items below:

· The drug product, a clear solution, in a 180 mL amber bottle with a closure mechanism that is child-resistant.
· The Press-In-Bottle-Adapter (PIBA Well) which will be inserted into the bottle by the pharmacist or has been manufactured with the PIBA in place.
· An Exacta-Med Dispenser^Ò which allows the patient to withdraw the appropriate dose of drug.
· Two dosing cups with child-resistant caps per shipment, one for each of two nightly doses.
· A Medication Guide.

E. Education Materials

1. Xyrem Physician Success Program

This program consists of printed material(s) to educate physicians about the features of Xyrem. When a physician prescribes the drug for the first time, the physician must verify that he/she has read these materials before the medication will be sent to the patient.

2. Xyrem Patient Success Program

This program consists of a videotape and printed educational material, which patients will receive from their physician or the pharmacy, prior to or together with the first shipment of drug. In addition, patients will be educated by either their physician or the pharmacy staff. The pharmacy will confirm that the patient has read and/or understood the educational materials.

Rev. 11/05

Xyrem^Ò (sodium oxybate)
CIII oral solution
SUCCESS PROGRAM^Ò for physicians

TABLE OF CONTENTS

Prescribing Xyrem ¾ A Brief Guide...............................................................................
Physician Registration Form..........................................................................................
Patient Prescription and Enrollment Form.....................................................................
Suggested Guidelines for Titrating Xyrem.....................................................................
Information You Need To Know About Xyrem................................................................
Success Program Contact Information..........................................................................

Package Insert and Medication Guide also included.

Please see full prescribing information for Xyrem (sodium oxybate) oral solution.

PRESCRIBING XYREM ¾ A BRIEF GUIDE

The procedure for writing and dispensing Xyrem prescriptions is outlined below. The central pharmacy with the Xyrem Success Program is always available at 1-866-XYREM88 (1-866-997-3688) to support you, your staff and your patients, and to answer any questions you might have.

Before Prescribing Xyrem

· Prescribing Xyrem requires entry into a physician registry.
· To do so, complete the enclosed Physician Registration Form and return it to the pharmacy.

Prescribing Requirements

· Confirm that each patient for whom you prescribe Xyrem has been educated with respect to Xyrem preparation, dosing and scheduling, and whether you have given the patient a copy of the patient education materials.
· Since optimal patient response often requires dose titration, you should evaluate your patients frequently during the early stages of treatment.
· The recommended starting dose is 4.5 grams nightly taken in equally-divided doses of 2.25 grams. Each patients dose may be titrated within the effective dose range of 6 to 9 grams/night.
· Once stable dosage is established, patients should be evaluated and prescriptions rewritten every 3 months

Prescription Form

· Fax the completed Xyrem Patient Prescription and Enrollment Form and all subsequent prescriptions to the pharmacy at 1-866-470-1744.
· Patients are entered in a registry maintained at the pharmacy

Central Pharmacys Role

Following receipt of your prescription, the pharmacy will:

· Send confirmation of each prescription received to your office.
· Request additional information or clarification if necessary.
· Contact the patients insurance provider to verify benefits and eligibility.
· Contact the patient to:
· confirm that you have educated the patient regarding the Xyrem Patient Success Program, and given the patient a copy of the education materials. If not, the pharmacy will educate the patient.
· confirm Xyrem delivery details.
· review preparation, administration and storage instructions.
· Dispense and ship Xyrem by overnight courier to the patient or his/her designee.
· Send Xyrem Patient Success Program materials to the patient with the first Xyrem shipment, if you have not already provided them.
· Maintain a patient and prescriber registry.

If you have any questions please call the Xyrem Physician Success Program at 1-866-XYREM88 (1-866-997-3688)

Please see full prescribing information for Xyrem (sodium oxybate) oral solution.

PHYSICIAN REGISTRATION FORM

XYREM^Ò SUCCESS PROGRAM PHYSICIAN REGISTRATION

Please check each box:

I have read the materials in the Xyrem Physician Success Program^Ò .

I understand that Xyrem^Ò (sodium oxybate) oral solution is approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy, and that safety or efficacy has not been established for any other indication.

I understand that the safety of doses greater than 9 g/day has not been established.

Please print clearly and fill out completely.

________________________________________________________________________
Prescribers Name                                          Prof. Designation (MD, DO, etc.) ________________________________________________________________________
Street Address 1

________________________________________________________________________
Street Address 2

________________________________________________________________________
City                                                                 State                                 Zip

________________________________________________________________________
Phone                                                              Fax

________________________________________________________________________
DEA Number                                                 Office Contact

Jazz Pharmaceuticals, Inc.

Rev 11/05

Xyrem^Ò (sodium oxybate) oral solution CIII
SUCCESS PROGRAM^Ò
Patient Prescription and Enrollment Form

Prescriber Information

Prescribers Name: _________________________             Office Contact: _____________________________
Street Address: ________________________________________________________________________
City: ____________________________________            State: __________________           Zip: ____________
Phone: ___________________________________           Fax: _____________________________________
License Number: ___________________________           DEA Number: ______________________________

Prescription Form

Patient Name: _____________________________            SS#: _____________           DOB: _______           Sex: M/F
Address:______________________________________________________________________________
City: _____________________________________          State: __________________           Zip: ____________
Rx: Xyrem^Ò Oral Solution (500 mg/mL)                               Quantity: _______ months supply
Total Nightly Dose: __________ gms

Sig: Take _____ mLs (_____ gms) p.o. diluted in 60 mL water at h.s. and then take _____ mLs (_____ gms) p.o. diluted in 60 mL water again 2 ½ to 4 hours later.

Conversion Table: 4.5 g = 4.5 mL twice nightly, 6 g = 6 mL twice nightly, etc.

Xyrem is medically appropriate for this patient.

Refills (circle one): 0 1 2 3 4 5

_________________________________________            Date: _____ / _____ / _____
Prescribers Signature

Please check each box To be completed at initial prescription only

I verify that the patient has been educated with respect to Xyrem preparation, dosing and scheduling.

I verify that the patient has received his/her own copy of the Patient Success Program materials (optional).

Patient Information

Best time to contact patient: Day Evening

Day #: __________________________________             Evening #: ________________________________
Insurance Company Name: __________________              Phone #: __________________________________
Insureds Name: __________________________              Relationship to Patient: ______________________
Identification Number: ______________________              Policy/Group Number: _______________________
Prescription Card: No Yes            If Yes, Carrier: ____________            Policy #: ___________            Group: ______

Please attach copies of patients insurance cards

Fax completed form to Xyrem Success Program (toll-free) 1-866-470-1744

For information, call the Xyrem Team (toll-free) at 1-866-XYREM88 (1-866-997-3688)

PS-XYR 58

Rev 11/05

SUGGESTED GUIDELINES FOR TITRATING XYREM

Xyrem (sodium oxybate) oral solution is indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.

Xyrem Dosing Considerations:

· It is a concentrated liquid that must be diluted with water (approximately 60 mL, 2 oz, ¼ cup, or 4 tablespoons).
· It is taken nightly in 2 equal doses.
· Both doses are prepared before bedtime in the provided dosing cups.
· Patients should be instructed to take their first Xyrem dose at bedtime.
· On awakening, 2½ ¾ 4 hours later, the second dose of Xyrem is taken before continuing sleep.
· Both doses should be taken when seated in bed.

Recommended Xyrem Titration

· The recommended starting dose is 4.5 grams per night (4.5 g = 9 mL total dose = two nightly doses of 4.5 mL each).

· Clinical trials have determined that Xyrem is effective in the dose range of 6 to 9 grams per night. Xyrem should be titrated in increments of 1.5 grams per night at one to two week intervals. If adverse effects occur, decrease dose by 1.5 grams per night.

· Dose titration may be required up to 9 grams per night.

· It is recommended that each dose titration not exceed 1.5 grams per night.

· It is recommended that review of dose response take place at one to two-week intervals until a stable dose is achieved.

· The maximum approved dose is 9 grams per night.

· Improvement may be expected during the first weeks of therapy. Titration to optimal dose may take up to 8 weeks.

NOTE: INSERT FLOWCHART

Please see full prescribing information for Xyrem (sodium oxybate) oral solution.

INFORMATION YOU NEED TO KNOW ABOUT XYREM

· Be diagnostically accurate. Confirm patients diagnosis of narcolepsy with cataplexy and/or excessive daytime sleepiness, particularly those patients new to you and/or your practice.

· Be judicious when deciding to increase a dose. Make sure the indicators are there for increasing or altering a dose.

· Be suspicious of a pattern of excuses for refills or repeated requests for refills on an emergency basis.

· Be vigilant. Recognize that there is potential for patients to abuse Xyrem.

Xyrem has been placed in a bifurcated Federal schedule. Xyrem is a Schedule III controlled substance when used for legitimate medical purposes, as prescribed. However, like all forms of GHB, Xyrem is classified as a Schedule I controlled substance when used for any other reason or by anyone other than for whom it was prescribed. Your patients should be informed that Federal law prohibits the transfer of Xyrem to any persons other than the patient for whom it was prescribed. If you have questions about this, please call the pharmacy at 1-866-XYREM88 (1-866-997-3688).

Please see full prescribing information for Xyrem (sodium oxybate) oral solution.

SUCCESS PROGRAM CONTACT INFORMATION

1-866-XYREM88 (1-866-997-3688)
Fax prescriptions to 1-866-470-1744

Xyrem^Ò(sodium oxybate) oral solution CIII
SUCCESS PROGRAM^Ò for physicians

Xyrem Success Program

For medical information, insurance reimbursement, prescription information, and any other questions, call the Xyrem Physician Success Program.

1-866-XYREM88^Ò
(1-866-997-3688)

Xyrem^Ò(sodium oxybate) CIII oral solution
SUCCESS PROGRAM^Ò for physicians

Dear Doctor:

Enclosed please find information regarding Xyrem (sodium oxybate) oral solution and the Xyrem Success Program. These materials are necessary to initiate Xyrem therapy for your patients.

First approved in July 2002, Xyrem is now indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. The active ingredient in Xyrem, sodium oxybate, is the sodium salt of gamma hydroxybutyrate (GHB). The use of illicit GHB has been associated with a number of serious central nervous system adverse clinical events, including seizures, respiratory depression, decreases in level of consciousness, confusion, and psychotic events. Because of these events, Xyrem has been approved for marketing under a risk management program that was developed in agreement with the Food & Drug Administration; this program is intended to educate physicians and patients and to prevent diversion. The Xyrem Success Program includes:

Patient Support

· Pharmacy services are provided by a central pharmacy, which handles all insurance coverage, product dispensing, mail order delivery and patient counseling.
· Patients are entered in a registry maintained at the pharmacy.
· Patients are educated prior to receiving their first Xyrem shipment.

Physician Support

· If you are prescribing Xyrem for the first time, you need to register with the Success Program. On the enclosed Physician Registration Form, please confirm that: 1) you have read the enclosed materials; 2) you understand Xyrem is approved for the treatment excessive daytime sleepiness and cataplexy in patients with narcolepsy; and 3) you understand that the safety of doses greater than 9 g/day has not been established.
· Xyrem prescriptions for new patients are to be written on the enclosed prescription form. This form should be filled out completely to ensure timely fulfillment of your patients prescription by the pharmacy.
· Be sure that you have provided Xyrem dosing, preparation, and administration counseling to each patient. You should also provide each patient with the Xyrem Patient

Success Program^Ò materials.

· It is also important for you to know that, just like all pharmacies that dispense controlled substances, the central pharmacy will maintain records about who is prescribing Xyrem. These records will be made available to any state or federal agency that requests them.
· Since optimal patient response often requires dose titration, we encourage you to evaluate your patients frequently during the early stages of treatment.
· Once stable dosage is established, we recommend patients be evaluated and prescriptions rewritten every 3 months. Note: the patients first Xyrem shipment will be limited to a 1-month supply and future shipments a 3-month supply.
· As with all prescription medications, we urge you to submit reports of all serious adverse reactions to the company.

If you require any additional assistance, please call the Xyrem Physician Success Program at 1-866-XYREM88 (1-866-997-3688).

Sincerely,

Philip Perera, M.D.
Chief Medical Officer
Vice President Clinical Research and Medical Affairs
Jazz Pharmaceuticals, Inc.

Please see full prescribing information for Xyrem (sodium oxybate) oral solution.

PHYSICIAN REGISTRATION FORM

XYREM^Ò SUCCESS PROGRAM PHYSICIAN REGISTRATION

Please check each box:

I have read the materials in the Xyrem Physician Success Program^Ò .

I understand that Xyrem^Ò (sodium oxybate) oral solution is approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy, and that safety or efficacy has not been established for any other indication.

I understand that the safety of doses greater than 9 g/day has not been established.

Please print clearly and fill out completely.

________________________________________________________________________
Prescribers Name                                           Prof. Designation (MD, DO, etc.)

________________________________________________________________________
Street Address 1

________________________________________________________________________
Street Address 2

________________________________________________________________________
City                                                                  State                                 Zip

________________________________________________________________________
Phone                                                               Fax

________________________________________________________________________
DEA Number                                                 Office Contact

Xyrem^Ò (sodium oxybate) CIII oral solution
SUCCESS PROGRAM for patients

Any questions? Please call 1-866-XYREM88 (1-866-997-3688) Xyrem Patient Success Program

Please see FDA-approved medication guide for more detailed information.>

Your doctor has prescribed Xyrem (sodium oxybate) oral solution.

Frequently asked questions about the use and safe handling of Xyrem

WHAT YOU WILL FIND IN THIS BOOKLET

Xyrem contains sodium oxybate, which has been shown to improve excessive daytime sleepiness and reduce the number of cataplexy attacks in patients with narcolepsy. This booklet answers important questions about obtaining, using, and storing Xyrem and precautions to be considered when doing so.

FILLING YOUR XYREM PRESCRIPTION....................................................................

How is my Xyrem prescription filled? ........................................................................................
What does the central pharmacy do?.......................................................................................
What will I receive with my shipment of Xyrem?.......................................................................
Can my local pharmacy provide Xyrem?....................................................................................
What does it mean that Xyrem is a controlled substance? ...................................................

INSURANCE COVERAGE...............................................................................................

Will insurance pay for Xyrem?....................................................................................................
What is the pharmacys role with my insurance?.....................................................................

HOW DO I TAKE XYREM?..............................................................................................

Preparing your doses..................................................................................................................
Taking your doses........................................................................................................................
What do I do if I miss a Xyrem dose?........................................................................................
How soon will I see a change in my symptoms?......................................................................
Are there side effects with Xyrem?............................................................................................
Are there any precautions that I should take while on Xyrem?..............................................
Can I take other medications with Xyrem?................................................................................
How often should my doctor check my progress with Xyrem? ...............................................

STORAGE AND SAFETY TIPS AT HOME......................................................................

Storage.......................................................................................................................................
Disposal......................................................................................................................................
Refills...........................................................................................................................................
Problems.....................................................................................................................................

TRAVELING TIPS.............................................................................................................

Before your trip..........................................................................................................................
During your trip..........................................................................................................................
Problems.....................................................................................................................................

NOTES..............................................................................................................................

GETTING MORE INFORMATION....................................................................................

Where can I get more information on Xyrem, narcolepsy, and other sleep disorders?.........The following organizations offer information on a wide range of sleep disorders..................... Medication Guide also included.

FILLING YOUR XYREM PRESCRIPTION

How is my prescription filled?

All Xyrem prescriptions are filled by a central, mail order pharmacy.

What does the central pharmacy do?.

· Your doctor sends the Xyrem prescription directly to the pharmacy.

· A team member from the pharmacy will contact you within 48 hours of receiving your prescription to review insurance information. For more information, see the section titled ²Insurance Coverage.²

· The pharmacy will confirm that you have received and/or understood this educational booklet. If your physician did not provide these materials to you, the pharmacy will review them with you before sending your first shipment of Xyrem.

· The pharmacy will always confirm where and when you would like Xyrem delivered and who will sign for the shipment. Xyrem will be shipped via an overnight courier. When the courier arrives you, or someone you designate, must sign for your Xyrem delivery.

What will I receive with my shipment of Xyrem?

With each shipment you receive, there will be 1 or more bottles of Xyrem, a liquid measuring device, 2 dosing cups with child-resistant caps and a printed medication guide.

Can my local pharmacy provide Xyrem?

No, but in some cases, you may be able to have the courier deliver Xyrem to your local pharmacy for later pickup.

What does it mean that Xyrem is a controlled substance?

The active ingredient of Xyrem, known as GHB, has been a target for persons who abuse drugs. Because Xyrem is a controlled substance, it is illegal for you to sell or give your Xyrem to anyone else, or to use your Xyrem for purposes other than it was prescribed. As with all controlled substances, failure to adhere to these rules may result in penalties as defined in the Controlled Substances Act.

Therefore, your Xyrem must be:

· used only by you.
· used only as directed by your physician.
· stored in a safe and secure place.

INSURANCE COVERAGE

Will insurance pay for my Xyrem?

In most cases, YES. A team member from the pharmacy will contact you and your insurance plan to coordinate your coverage for Xyrem.

What is the pharmacys role with my insurance?

An experienced Reimbursement Specialist will:

· call you to review your benefits and eligibility.

· inform you of your co-pay responsibility, if applicable.

· obtain prior authorization from your insurance company, if needed.

· file appropriate appeals on your behalf. assist with obtaining alternate funding that may be available to you.

· support you with all aspects of insurance.

The pharmacys attempt to obtain coverage from a patients third-party payer does not constitute or guarantee success.

HOW DO I TAKE XYREM?

Xyrem is to be taken only as directed by your doctor.

Xyrem should be taken twice nightly: the first dose is taken at bedtime and the second dose is taken 2½ to 4 hours later. Both doses should be taken while seated in bed.

Preparing your doses

Before going to bed, draw up each of your Xyrem doses with the provided measuring device and empty into the two dosing cups. Dilute each dose with about 2 oz of water (about 60mL, ¼ cup, or 4 tablespoons). Then place the child-resistant caps onto the dosing cups and put them in a safe place by your bed, out of the reach of children and pets.

Taking your doses

· Food will decrease the amount of Xyrem that is absorbed. Therefore, you should allow about two hours after a meal before taking your first dose of Xyrem.
· Xyrem is a medicine that produces sleepiness; therefore, as a safety precaution, it is best to be in bed when you take your first dose. As with any medicine that causes sleepiness, if you continue evening activities after taking your dose, such as watching television or walking around, you may experience light-headedness, dizziness, nausea, confusion or other unpleasant feelings.
· 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 hours, turn off your alarm and take your second dose.

What do I do if I miss a Xyrem dose?

· Never take 2 doses of Xyrem at once to make up for a missed dose.
· Leave a minimum of 2½ hours between each nightly dose.
· Remember not to engage in activities requiring mental alertness within 6 hours of dosing.

How soon will I see a change in my symptoms?

You can expect to see some improvement in your symptoms shortly after beginning Xyrem therapy. If you are not experiencing any change in your symptoms, contact your doctor for assessment and possible dose adjustment. Individual symptom response may vary and it may take several weeks to achieve the maximum beneficial effect of Xyrem.

You and your doctor will discuss your response to treatment, and your doctor may increase or decrease your dose as a result. NEVER CHANGE THE DOSE OF XYREM YOURSELF.

Are there side effects with Xyrem?

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

If you experience the following side effects while using Xyrem, you should promptly call your doctor: confusion, vomiting, sleep walking, breathing problems (at night), depression or abnormal thinking.

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

Are there any precautions I should take while on Xyrem?

· While taking Xyrem, you should not drink alcoholic beverages or take medications that cause drowsiness.
· Do not drive a car, operate heavy machinery or perform any activity that is dangerous or requires mental alertness, for at least 6 hours after taking Xyrem. When you first start taking Xyrem, use extreme care while performing these activities until you know whether it makes you sleepy the next day.
· Before starting Xyrem, tell your healthcare provider if you are pregnant, breast-feeding or plan to become pregnant. It is not known whether Xyrem can pass through your milk.
· Keep your Xyrem in a secure location, out of the reach of children. Xyrem does not require refrigeration.

Can I take other medications with Xyrem?

Xyrem should not be used in combination with alcohol or medications that can cause drowsiness. You should tell your doctors and pharmacist about any other medicines you are currently taking, including non-prescription medicines and any vitamins or herbal, nutritional or dietary supplements.

It is also important to tell other health care providers that you are taking Xyrem before starting or changing any medications.

How often should my doctor check my progress with Xyrem?

When you first start taking Xyrem, you may need to talk to your doctor frequently until he or she has determined the best dose for you. You can expect that your dose may need to be adjusted. After your dose has been established, your doctor should check your progress at least every 3 months while you are taking Xyrem.

STORAGE AND SAFETY TIPS AT HOME

Storage

· Always keep Xyrem in its original container.

· Xyrem can be stored at room temperature.

· Like all medications, Xyrem should be kept in a secure location out of the reach of children and pets. In case of accidental ingestion, call the poison center at 1-800-222-1222 or dial 911.

Disposal

· When you can no longer draw medication out of the bottle with the measuring device, it is time to throw the bottle away. Pour any unused Xyrem down the drain. Scribble over the label with a marker before putting it in the trash so someone else cannot use it for illegal purposes.

Refills

· Remember to reorder your Xyrem when you have only a 7-day supply remaining. Call the pharmacy at 1-866-997-3688 to request a refill.

Problems

· If your supply of Xyrem is lost or stolen, please report the incident immediately to the local police and the pharmacy.

· Use only as directed. Remember that use of your Xyrem by others is illegal.

· If you have questions, concerns, or need advice regarding Xyrem, call your doctor or the pharmacy.

TRAVELING TIPS¼

Before your trip

· When packing for your trip, be sure to take enough Xyrem for the length of time you will be away.

· Always travel with Xyrem in its original container, with the pharmacy label on it.

· Take only the number of bottles of Xyrem needed for your stay away from home. Be sure that any Xyrem bottles left behind are in a secure place before you leave home.

During your trip

· Do not pack your Xyrem in a suitcase that will be checked baggage. Keep it in a secure location when it is not in your possession.

· Remember to take your dispensing device and the dosing cups with child-resistant caps when traveling. In an unfamiliar environment, it is especially important that your second nightly dose of Xyrem is not left in an unsecured place or within the reach of children or pets.

· When you pack to return home, do not forget your Xyrem.

· If you should forget your Xyrem while traveling within the United States or need more due to an extended stay, call the pharmacy at 1-866-997-3688.

· If traveling internationally, be aware that Xyrem may be subject to different regulations in other countries. Always travel with Xyrem in its original container, with the pharmacy label on it.

Problems

· If your supply of Xyrem is lost or stolen while traveling, please report the incident immediately to the local police and the pharmacy.

If you have questions, concerns, or need advice regarding Xyrem while traveling, call the pharmacy.

Xyrem Success Program Contact Information

1-866-XYREM88 (1-866-997-3688)

FAX 1-866-470-1744

For international access call the pharmacy at + 314-918-6600

NOTES¼

GETTING MORE INFORMATION¼

Where can I get more information on Xyrem, narcolepsy, and other sleep disorders?

For more information on Xyrem, please call your help line at 1-866-XYREM88 (1-866-997-3688) or visit the Xyrem Web site at http://www.xyrem.info.

The following organizations offer information on a wide range of sleep disorders:

Jazz Pharmaceuticals, Inc.
3180 Porter Drive
Palo Alto, CA 94304
Phone: 1-866-XYREM88

www.advocatesforsleep.com

Advocates for Sleep
818 West 46^th Street, Suite 203
Minneapolis, MN 55419
Phone: 1-800-823-8893

www.talkaboutsleep.com

Talk About Sleep, Inc.
818 West 46^th Street, Suite 203
Minneapolis, MN 55419
Phone: 612-822-6896
Fax: 612-822-6875

www.rarediseases.org

NORD (National Organization for Rare Disorders)
55 Kenosia Avenue
P.O. Box 1968
Danbury, CT 06813-1968
Phone: 1-800-999-6673

www.sleepfoundation.org

National Sleep Foundation
1522 K Street NW, Suite 500
Washington, DC 20005
Phone: 202-347-3471

www.narcolepsynetwork.org

Narcolepsy Network, Inc.
79A Main Street
North Kingstown, RI 02852
Phone: 888-292-6522
Fax: 401-633-6567

E-mail: narnet@ narcolepsynetwork.org

Keep this booklet as a helpful reminder. If you have questions or need information, dont hesitate to contact the pharmacy with the Xyrem Success Program.

1-866-XYREM88 (1-866-997-3688)

FAX 1-866-470-1744

Xyrem^Ò (sodium oxybate) CIII oral solution
SUCCESS PROGRAM^Ò for patients

Dear Patient,

Welcome to the Xyrem Success Program. Your doctor recently prescribed Xyrem (sodium oxybate) oral solution for you. We have developed the Xyrem Patient Success Program to support you as you start your treatment. The program includes the enclosed Xyrem Patient Success Program booklet, other educational materials and a toll-free phone number: 1-866-XYREM88^Ò (1-866-997-3688). The educational materials contain important information on obtaining, using and storing Xyrem.

Xyrem is a medication that has been approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. Important information about Xyrem includes the following:

· Twice nightly dosing: the first dose is taken at bedtime and the second dose 2½ - 4 hours later
· Both doses should be taken while sitting up in bed
· Xyrem should not be taken with alcohol or other medications that cause drowsiness
· Your Xyrem prescription is filled and sent by a central, mail order pharmacy
· The active ingredient of Xyrem, known as GHB, has been a target for persons who abuse drugs. Therefore your Xyrem must be used only by you, only as directed by your physician, and stored in a safe, secure place.

A team member from the pharmacy will call you within 48 hours of receiving your prescription to review your insurance information. It is important that you take this call in order to receive your prescription. A pharmacist is also available to discuss any questions you may have.

To support you in obtaining and using Xyrem, we have developed the Xyrem Patient Success Program which includes the enclosed educational materials. We hope that you will find this information helpful.

Yours sincerely,

Philip Perera, M.D.
Chief Medical Officer

Vice President Clinical Research and Medical Affairs
Jazz Pharmaceuticals, Inc.

Xyrem^Ò (sodium oxybate) oral solution CIII
SUCCESS PROGRAM^Ò
Patient Prescription and Enrollment Form

Prescriber Information

Prescribers Name: __________________________ Office Contact: _____________________________ Street Address: ________________________________________________________________________ City: _____________________________________ State: __________________ Zip: ____________ Phone: ___________________________________ Fax: _____________________________________ License Number: ___________________________ DEA Number: ______________________________

Prescription Form

Patient Name: _____________________________ SS#: _____________ DOB: _______ Sex: M/F

Address:______________________________________________________________________________

City: _____________________________________ State: __________________ Zip: ____________

Rx: Xyrem^Ò Oral Solution (500 mg/mL) Quantity: _______ months supply

Total Nightly Dose: __________ gms

Sig: Take _____ mLs (_____ gms) p.o. diluted in 60 mL water at h.s. and then take _____ mLs (_____ gms) p.o. diluted in 60 mL water again 2 ½ to 4 hours later.

Conversion Table: 4.5 g = 4.5 mL twice nightly, 6 g = 6 mL twice nightly, etc.

Xyrem is medically appropriate for this patient.

Refills (circle one): 0 1 2 3 4 5

_________________________________________ Date: _____ / _____ / _____

Prescribers Signature

Please check each box To be completed at initial prescription only

I verify that the patient has been educated with respect to Xyrem preparation, dosing and scheduling.

I verify that the patient has received his/her own copy of the Patient Success Program materials (optional).

Patient Information

Best time to contact patient: Day Evening

Day #: ____________________________________ Evening #: ________________________________ Insurance Company Name: ___________________ Phone #: __________________________________ Insureds Name: ____________________________ Relationship to Patient: ______________________ Identification Number: _______________________ Policy/Group Number: _______________________ Prescription Card: No Yes If Yes, Carrier: ____________ Policy #: ___________ Group: ______

Please attach copies of patients insurance cards

Fax completed form to Xyrem Success Program (toll-free) 1-866-470-1744

For information, call the Xyrem^Ò Team (toll-free) at 1-866-XYREM88^Ò (1-866-997-3688)