Risk Evaluation and Mitigation Strategy (REMS) Document
`
`XYWAV (calcium, magnesium, potassium, and sodium oxybates)
`and XYREM (sodium oxybate) REMS Program
`
`I. Administrative Information
`
`Application Numbers: NDA 21196; NDA 212690
`Application Holder: Jazz Pharmaceuticals, Inc (NDA 21196); Jazz Pharmaceuticals Ireland, Ltd. (NDA
`212690)
`Initial REMS Approval: 02/2015
`Most Recent REMS Update: [07/2020]
`
`II. REMS Goal
`
`The goal of the XYWAV and XYREM REMS is to mitigate the risks of serious adverse outcomes resulting
`from inappropriate prescribing, misuse, abuse, and diversion of XYWAV and XYREM by:
`
`1. Informing prescribers, pharmacists, and patients of:
`
`a. The risk of significant CNS and respiratory depression associated with XYWAV and XYREM
`
`b. The contraindication of use of XYWAV and XYREM with sedative hypnotics and alcohol
`
`c. The potential for abuse, misuse, and overdose associated with XYWAV and XYREM
`
`d. The safe use, handling, and storage of XYWAV and XYREM
`
`2. Ensuring that pharmacy controls exist prior to filling prescriptions for XYWAV and XYREM that:
`
`a. Screen for concomitant use of sedative hypnotics and other potentially interacting agents
`
`b. Monitor for inappropriate prescribing, misuse, abuse, and diversion of XYWAV and XYREM
`
`c. Notify prescribers when patients are receiving concomitant contraindicated medications or
`there are signs of potential abuse, misuse, or diversion
`
`III. REMS Requirements
`
`Jazz Pharmaceuticals must ensure that healthcare providers, patients, and the pharmacy
`comply with the following requirements:
`
`1. Healthcare providers who prescribe XYWAV and XYREM must:
`
`To become
`certified to
`prescribe
`
`1. Review the XYWAV and XYREM Prescribing Information.
`
`2. Review the following: Prescriber Brochure.
`
`3. Enroll in the REMS by completing the Prescriber Enrollment Form and
`submitting it to the REMS Program.
`
`Before treatment
`initiation (first
`dose)
`
`4. Assess the patient’s health status to determine if XYWAV or XYREM is
`medically appropriate by screening for history of alcohol or substance abuse,
`sleep-related breathing disorders, compromised respiratory function, and
`depression or suicidality.
`
`Reference ID: 4644289
`
`Page 1 of 9
`
`

`

`1. Healthcare providers who prescribe XYWAV and XYREM must:
`
`5. Assess the patient’s health status to determine if XYWAV or XYREM is
`medically appropriate by screening for concomitant use of sedative hypnotics,
`other CNS depressants, or other potentially interacting agents. Document and
`submit to the REMS Program using the product-specific Prescription Form.
`
`6. Counsel the patient on the serious risks associated with XYWAV and XYREM
`safe use, handling, and storage using the XYWAV Patient Quick Start Guide,
`XYREM Patient Quick Start Guide, XYWAV Brochure for Pediatric Patients and
`their Caregivers, or XYREM Brochure for Pediatric Patients and their
`Caregivers.
`
`7. Enroll the patient by completing and submitting the Patient Enrollment Form
`to the REMS Program.
`
`8. Order the prescription using either the XYWAV Prescription Form or XYREM
`Prescription Form and submit it to the REMS Program.
`
`Before treatment
`re-initiation
`
`9. For patients dis-enrolled for suspicion of abuse, misuse or diversion:
`communicate with the pharmacy and agree it is appropriate to re-enroll the
`patient.
`
`During treatment;
`within the first 3
`months of starting
`treatment and
`recommended
`every 3 months
`thereafter
`
`At all times
`
`10. For patients with a lapse in treatment of 6 months or longer: order the
`prescription using either the XYWAV Prescription Form or XYREM Prescription
`Form and submit it to the REMS program.
`
`11. Assess the patient for: concomitant use of sedative hypnotics, other CNS
`depressants, or potentially interacting agents; serious adverse events; and
`signs of abuse and misuse including an increase in dose or frequency of
`dosing, reports of lost, stolen, or spilled medication, and drug-seeking
`behavior.
`
`12. Report all potential serious adverse events, including CNS depression,
`respiratory depression, loss of consciousness, coma, and death, and any cases
`of suspected abuse, misuse, or diversion to Jazz Pharmaceuticals.
`
`Reference ID: 4644289
`
`Page 2 of 9
`
`

`

`2. Patients who are prescribed XYWAV and XYREM:
`
`Before treatment
`initiation
`
`1. Review the XYWAV Patient Quick Start Guide, XYREM Patient Quick Start
`Guide, XYWAV Brochure for Pediatric Patients and their Caregivers, or XYREM
`Brochure for Pediatric Patients and their Caregivers.
`
`2. Receive counseling from the prescriber on the serious risks associated with
`XYWAV and XYREM and safe use, handling, and storage of XYWAV and XYREM
`using the XYWAV Patient Quick Start Guide, XYREM Patient Quick Start Guide,
`XYWAV Brochure for Pediatric Patients and their Caregivers, or XYREM
`Brochure for Pediatric Patients and their Caregivers.
`
`3. Enroll in the REMS Program by completing the Patient Enrollment Form with
`the prescriber. Enrollment information will be provided to the REMS Program.
`
`4. Complete the Patient Counseling Checklist with the pharmacist.
`
`During treatment
`
`5. Adhere to the safe use conditions described in the XYWAV Patient Quick Start
`Guide, XYREM Patient Quick Start Guide, XYWAV Brochure for Pediatric
`Patients and their Caregivers, or XYREM Brochure for Pediatric Patients and
`their Caregivers.
`
`6. Complete the Patient Counseling Checklist with the pharmacist based on
`changes in your medication and/or medical history.
`
`During treatment;
`within the first 3
`months of
`starting treatment and
`recommended every 3
`months thereafter
`
`7. Be monitored for concomitant use of sedative hypnotics, other CNS
`depressants, or potentially interacting agents; serious adverse events; signs of
`abuse and misuse including an increase in dose or frequency of dosing; reports
`of lost, stolen, or spilled medication; and drug-seeking behavior.
`
`Before treatment re-
`initiation,
`after lapse in
`treatment for 6
`months or longer
`
`At all times
`
`8. Complete the Patient Counseling Checklist with the pharmacist.
`
`9.
`
`Inform your prescriber and the pharmacy about any new medications you may
`be taking or medical conditions you may have.
`
`Reference ID: 4644289
`
`Page 3 of 9
`
`

`

`3.The pharmacy that dispenses XYWAV and XYREM must:
`
`To become certified
`to dispense
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`For all relevant staff involved in dispensing: review the Pharmacy Training
`Program – Module A.
`
`For all relevant staff involved in dispensing: successfully complete the
`Module A Knowledge Assessment and submit it to the REMS Program.
`
`For all pharmacists involved in dispensing: review the Pharmacy Training
`Program – Module A and B.
`
`For all pharmacists involved in dispensing: successfully complete the
`Module A Knowledge Assessment and Module B Knowledge Assessment
`and submit it to the REMS Program.
`
`Train all pharmacists involved in dispensing per the requirements of the
`Pharmacy Training Program – Module B.
`
`Establish processes and procedures to verify the following: the patient and
`prescriber are enrolled, the patient has no other active XYWAV or XYREM
`prescriptions.
`
`Establish processes and procedures to verify all the prescription
`information including patient name and two additional identifiers,
`prescriber name and information, dose, titration information (if
`applicable), number of refills, dosing directions, total quantity (days’
`supply), and concomitant medications.
`
`Establish processes and procedures to assess the patient’s concomitant
`use of sedative hypnotics, other CNS depressants, or other potentially
`interacting agents that either are unknown to the prescriber or pose a
`high risk of serious interaction.
`
`Establish processes and procedures to provide 24-7 toll-free access to a
`XYWAV and XYREM REMS Program pharmacist; to dispense no more than
`a one-month supply for the initial shipment and no more than a three-
`month supply for subsequent shipments; and to ship, track, and verify
`receipt of XYWAV and XYREM to the patient or patient-authorized adult
`designee using an overnight service.
`
`Reference ID: 4644289
`
`Page 4 of 9
`
`

`

`Before dispensing
`
`10.
`
`For new patients and existing patients who restart treatment after not
`receiving XYWAV or XYREM for 6 months or longer: Counsel the patient
`using the Patient Counseling Checklist. Document and submit to the REMS
`Program using the Central Database.
`
`11.
`
`12.
`
`13.
`
`14.
`
`15.
`
`For patients who report a change in their medication use or medical
`history: document and submit to the REMS Program using the Central
`Database.
`
`Assess the patient’s concomitant use of sedative hypnotics, other CNS
`depressants, or other potentially interacting agents that either are
`unknown to the prescriber or pose a high risk of serious interaction using
`the processes and procedures established as a requirement of the REMS
`Program.
`
`Verify in the Central Database that the patient and prescriber are enrolled
`and that the patient has no other active XYWAV or XYREM prescriptions
`through the processes and procedures established as a requirement of the
`REMS Program.
`
`For patients previously dis-enrolled for suspicion of abuse, misuse or
`diversion: communicate all relevant patient history to the prescriber and
`re-enroll the patient if the prescriber and pharmacist agree.
`
`Verify the patient’s prescription information, including patient name and
`two additional identifiers, prescriber name and information, dose, titration
`information (if applicable), number of refills, dosing directions, total
`quantity (days’ supply), and concomitant medications through the
`processes and procedures established as a requirement of the REMS
`Program.
`
`16.
`
`Assess the patient’s potential for abuse, misuse, and diversion by
`reviewing the alerts and Risk Management Report history in the Central
`Database.
`
`17.
`
`For patients who request an early refill or if abuse, misuse or diversion is
`suspected: Discuss the request or concern with the prescriber.
`
`18. Dispense no more than a one months’ supply for the initial shipment.
`
`19. Dispense no more than a three months’ supply for subsequent shipments.
`
`Before Shipping
`
`20.
`
`Verify the patient’s shipping address and that the patient or patient-
`authorized adult designee will be available to receive the shipment
`through the processes and procedures established as a requirement of the
`REMS.
`
`21.
`
`22.
`
`Ship XYWAV and XYREM directly to each patient or a patient-authorized
`adult designee through the processes and procedures established as a
`requirement of the REMS.
`
`Provide the patient with the XYWAV Patient Quick Start Guide, XYREM
`Patient Quick Start Guide, XYWAV Brochure for Pediatric Patients and their
`Caregivers, or XYREM Brochure for Pediatric Patients and their Caregivers
`with the first shipment.
`
`Reference ID: 4644289
`
`Page 5 of 9
`
`

`

`After Shipping
`
`23.
`
`Track and verify receipt of each shipment of XYWAV and XYREM through
`the processes and procedures established as a requirement of the REMS.
`
`24. Document and submit the shipment and receipt dates to the Central
`Database.
`
`To Maintain
`Certification to
`Dispense, Every Year
`
`At all times
`
`25.
`
`26.
`
`27.
`
`28.
`
`For all relevant staff involved in dispensing: review the Pharmacy Training
`Program – Module A.
`
`For all relevant staff involved in dispensing: successfully complete the
`Module A Knowledge Assessment and submit it to the REMS Program.
`
`For all pharmacists involved in dispensing: review the Pharmacy Training
`Program – Modules A and B.
`
`For all pharmacists involved in dispensing: successfully complete the
`Module A Knowledge Assessment and Module B Knowledge Assessment
`and submit it to the REMS Program.
`
`29.
`
`Train all pharmacists involved in dispensing on the requirements of the
`REMS Program using Pharmacy Training Program – Module B.
`
`30.
`
`31.
`
`32.
`
`33.
`
`34.
`
`Provide 24-7 toll-free access to a XYWAV and XYREM REMS Program
`pharmacist.
`
`Ship XYWAV or XYREM directly to the patient or a patient-authorized adult
`designee using an overnight service.
`
`Document and report all potential adverse events reported by all sources,
`including any CNS depression, respiratory depression, loss of
`consciousness, coma, and death to Jazz Pharmaceuticals.
`
`Report lost, stolen, destroyed, or spilled drug to the Central Database
`using the Risk Management Report.
`
`Monitor for all instances of patient and prescriber behavior that give rise
`to a reasonable suspicion of abuse, misuse, and diversion, including all
`requests for early refills, and all reports of lost, stolen, destroyed, or
`spilled drug. Report to Jazz Pharmaceuticals by documenting into the
`Central Database using the Risk Management Report.
`
`35.
`
`Not distribute, transfer, loan, or sell XYWAV or XYREM.
`
`36.
`
`Not stock XYWAV or XYREM in retail pharmacies.
`
`37.
`
`38.
`
`Maintain records documenting staff’s completion of the Pharmacy Training
`Program.
`
`Comply with audits carried out by Jazz Pharmaceuticals or a third party
`acting on behalf of Jazz Pharmaceuticals to ensure that all processes and
`procedures are in place and are being followed.
`
`Reference ID: 4644289
`
`Page 6 of 9
`
`

`

`Jazz Pharmaceuticals must provide training to healthcare providers who prescribe XYWAV and
`XYREM.
`The training includes the following educational material: Prescriber Brochure. The training must be
`available on a website or delivered by Jazz Pharmaceuticals.
`
`Jazz Pharmaceuticals must provide training to the pharmacy that dispenses XYWAV and
`XYREM.
`The training includes the following educational materials: Certified Pharmacy Training Program-Module A
`and B, Module A Knowledge Assessment, and Module B Knowledge Assessment. The training must be
`available on a website or delivered by Jazz Pharmaceuticals.
`
`To support REMS Program operations, Jazz Pharmaceuticals must:
`1.
`Certify a pharmacy through a contract and distribute XYWAV and XYREM only to the certified
`pharmacy for dispensing.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Not stock XYWAV or XYREM in retail pharmacies.
`
`Establish and maintain a REMS Program website, www.XYWAVXYREMREMS.com. The REMS Program
`website must include the capability to complete prescriber certification and patient enrollment, and
`the option to print the Prescribing Information and REMS materials. All product websites for
`consumers and healthcare providers must include prominent REMS-specific links to the REMS
`Program website. The REMS Program website must not link back to the promotional product
`website(s).
`
`Make the REMS Program website fully operational and all REMS materials available through the
`website or call center within 180 calendar days of REMS modification (07/21/2020).
`
`Establish and maintain a REMS Program call center for REMS participants at 1-866-997-3688.
`
`Establish and maintain a validated, secure database, called the Central Database, of all REMS
`participants who have been or are enrolled and/or certified in the XYWAV and XYREM REMS Program.
`The database must include the following information: prescriber and patient enrollment status, all
`completed forms, prescription and shipment data as well as dosing, concomitant medications,
`behavior that raises suspicion of abuse, misuse, or diversion including all alerts and risk
`management reports.
`
`Ensure prescribers are able to submit the Prescriber Enrollment Form by facsimile, mail, email, and
`online.
`
`Ensure prescribers are able to submit the Patient Enrollment Form by facsimile, mail, and online.
`
`Ensure prescribers are able to submit the Prescription Form by facsimile and mail.
`
`10. Ensure prescribers are able to add refills and renew prescriptions by phone, facsimile, mail, and
`electronically
`
`11. Ensure pediatric patients are able to change caregivers provided that the new caregiver has been
`counseled by the pharmacy on the serious risks and safe use of XYWAV and XYREM and
`acknowledges that he/she had any questions about XYWAV and XYREM answered before drug
`product is dispensed and shipped.
`
`12. Ensure patients are able to change prescribers.
`
`13. Ensure that the pharmacy is able to report lost, stolen, destroyed or spilled drug by completing a
`Risk Management Report in the Central Database.
`
`Reference ID: 4644289
`
`Page 7 of 9
`
`

`

`14. Ensure that the pharmacy is able to report repeated incidents of lost, stolen, destroyed, or spilled
`drug by creating an alert on the patient’s profile in the Central Database.
`
`15. Ensure that the pharmacy is able to disenroll patients, in consultation with the prescriber and/or Jazz
`Pharmaceuticals, after review of incidents suggestive of abuse, misuse, or diversion by changing the
`patient’s enrollment status in the Central Database.
`
`16. Notify Prescribers within 2 business days after they become certified in the REMS Program.
`
`17. Provide the certified pharmacy access to the database of certified prescribers and enrolled patients.
`
`To ensure REMS participants’ compliance with the REMS Program, Jazz Pharmaceuticals must:
`18. Maintain adequate records to demonstrate that REMS requirements have been met, including, but
`not limited to records of: XYREM distribution and dispensing; XYWAV distribution and dispensing,
`certification of prescribers, and the certified pharmacy; enrolled patients; and audits of REMS
`participants. These records must be readily available for FDA inspections.
`
`19. Ensure that a prescriber is enrolled in the REMS Program only after verification that the Prescriber
`Enrollment Form is complete and all enrollment requirements are met.
`
`20. Establish a plan for addressing noncompliance with REMS Program requirements.
`
`21. Monitor prescribers and the certified pharmacy on an ongoing basis to ensure the requirements of
`the REMS are being met. Take corrective action if non-compliance is identified, including de-
`certification.
`
`22. Monitor the certified pharmacy for timely reporting to Jazz Pharmaceuticals of all potential adverse
`events and any behavior by patients or prescribers enrolled in the REMS Program that raises
`suspicion of abuse, misuse or diversion.
`
`23. Monitor the Central Database on an ongoing basis to ensure the requirements of the REMS are being
`met. Take corrective action if non-compliance is identified.
`
`24. Audit the certified pharmacy at least annually.
`
`25. Take reasonable steps to improve implementation of and compliance with the requirements in the
`XYWAV and XYREM REMS Program based on monitoring and evaluation of the XYWAV and XYREM
`REMS Program.
`
`IV. REMS Assessment Timetable
`
`Jazz Pharmaceuticals must submit REMS Assessments every 6 months from the date of the REMS approval
`(02/2015) for the first year, and annually thereafter. To facilitate inclusion of as much information as
`possible while allowing reasonable time to prepare the submission, the reporting interval covered by each
`assessment should conclude no earlier than 60 calendar days before the submission date for that
`assessment. Jazz Pharmaceuticals must submit each assessment so that it will be received by the FDA on
`or before the due date.
`
`V. REMS Materials
`
`The following materials are part of the XYWAV and XYREM REMS:
`
`Enrollment Forms
`Prescriber:
`1.
`Prescriber Enrollment Form
`
`Patient:
`
`Reference ID: 4644289
`
`Page 8 of 9
`
`

`

`2.
`
`Patient Enrollment Form
`
`Training and Educational Materials
`Prescriber:
`3.
`Prescriber Brochure
`
`Patient:
`4.
`XYREM Patient Quick Start Guide
`
`5.
`
`6.
`
`7.
`
`XYREM Brochure for Pediatric Patients and their Caregivers
`
`XYWAV Patient Quick Start Guide
`
`XYWAV Brochure for Pediatric Patients and their Caregivers
`
`Pharmacy
`
`8.
`
`9.
`
`Certified Pharmacy Training Program
`
`Module A Knowledge Assessment
`
`10. Module B Knowledge Assessment
`
`Patient Care Forms
`11. XYREM Prescription Form
`
`12. XYWAV Prescription Form
`
`13. Patient Counseling Checklist
`
`Other Materials
`14. Risk Management Report
`
`15. REMS Program website
`
`Reference ID: 4644289
`
`Page 9 of 9
`
`

`

`XYWAV and XYREM REMS PRESCRIBER ENROLLMENT FORM
`XYWAV™ (calcium, magnesium, potassium, and sodium oxybates) oral solution, 0.5 g/mL
`XYREM® (sodium oxybate) oral solution 0.5 g/mL
`Complete and submit form online at www.XYWAVXYREMREMS.com, OR scan and e-mail to
`ESSDSPrescribers@express-scripts.com, OR fax to XYWAV and XYREM REMS at 1-866-470-1744
`(toll free), OR mail to XYWAV and XYREM REMS, PO Box 66589, St. Louis, MO 63166-6589.
`For more information, please call the XYWAV and XYREM REMS at 1-866-997-3688 (toll free).
`Note: Completion of this form and enrollment in the REMS allows you to prescribe both XYWAV and XYREM.
`Step 1: ALL BOXES BELOW MUST BE CHECKED (
`) IN ORDER FOR THE ENROLLMENT PROCESS TO BE
`COMPLETE AND BEFORE YOU CAN ENROLL PATIENTS AND PRESCRIBE XYWAV or XYREM.
` F I understand that XYWAV and XYREM are indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in
`patients 7 years of age and older with narcolepsy.
` F I have read the Prescribing Information (PI) and the XYWAV and XYREM REMS Prescriber Brochure and understand that:
` — XYWAV and XYREM are Schedule III CNS depressants and can cause obtundation and clinically significant respiratory
`depression at recommended doses
` — The use of XYWAV or XYREM in combination with alcohol or sedative hypnotics is contraindicated.
` — Concurrent use of XYWAV or XYREM with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines,
`sedating antidepressants or antipsychotics, sedating anti-epileptics, general anesthetics, muscle relaxants, and/or illicit CNS
`depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death
` — Patients who have sleep apnea or compromised respiratory function (e.g., asthma, COPD, etc.) may be at higher risk of
`developing respiratory depression, loss of consciousness, coma, and death with XYWAV or XYREM use
` F I agree to:
` — Enroll each patient in the XYWAV and XYREM REMS
` — Screen each patient for history of alcohol or substance abuse, sleep-related breathing disorders, compromised respiratory
`function, depression, suicidality, and concomitant use of sedative hypnotics, other CNS depressants, or other potentially
`interacting agents
` — Counsel each patient and/or caregiver prior to initiating therapy on the serious risks and safe use, handling, and storage of
`XYWAV or XYREM
` — Evaluate patients within the first 3 months of starting XYWAV or XYREM. It is recommended that patients be re-evaluated
`every 3 months thereafter while taking XYWAV or XYREM
` — Report all potential serious adverse events, including CNS depression, respiratory depression, loss of consciousness, coma,
`and death, and any cases of suspected abuse, misuse, or diversion to Jazz Pharmaceuticals
`Step 2: To help expedite the enrollment process, please PRINT clearly (*denotes required field).
`Prescriber Information
`
`*First Name:
`
`*DEA No.:
`
`Facility/Practice Name:
`
`*Street Address:
`
`*City:
`
`*Phone:
`
`M.I.:
`
`*Last Name:
`
`Prof. Designation (MD, DO, PA, NP):
`
`*State License No.:
`
`*NPI no.:
`
`*State:
`
`*Zip Code:
`
`*Fax:
`
`E-mail:
`
`Office Contact Phone:
`Office Contact:
`Additional office locations and contacts can be entered online at XYWAVXYREMREMS.com.
`
`Step 3: Prescriber signature is required below for enrollment in the XYWAV and XYREM REMS.
`By signing below, I acknowledge the above attestations, and I understand that my personally identifiable information provided above
`will be shared with Jazz Pharmaceuticals, Inc., its agents, contractors, and affiliates and entered into a prescriber database for the
`XYWAV and XYREM REMS. I agree that I may be contacted in the future by mail, e-mail, fax, and/or telephone concerning XYWAV,
`XYREM, and the XYWAV and XYREM REMS.
`
`*Prescriber Signature:
`
` *Date:
`
`Report SERIOUS ADVERSE EVENTS by contacting Jazz Pharmaceuticals at 1-800-520-5568 or jazzsafety@jazzpharma.com.
`
`Reference ID: 4644289
`
`

`

`XYWAV and XYREM REMS PATIENT ENROLLMENT FORM
`XYWAV™ (calcium, magnesium, potassium, and sodium oxybates) oral solution, 0.5 g/mL
`XYREM® (sodium oxybate) oral solution 0.5 g/mL
`Complete and submit form online at www.XYWAVXYREMREMS.com, OR scan and e-mail to
`ESSDSPrescribers@express-scripts.com, OR fax to XYWAV and XYREM REMS at 1-866-470-1744 (toll free),
`OR mail to: XYWAV and XYREM REMS, PO Box 66589, St. Louis, MO 63166-6589.
`For more information, please call the XYWAV and XYREM REMS at 1-866-997-3688 (toll free).
`Note: Use this form to enroll patients in the XYWAV and XYREM REMS for either product.
`Please Print (*denotes required field)
`
`*First Name:
`
`*Street Address:
`
`*City:
`
`Office Contact:
`
`Prescriber Information
`
`M.I.:
`
`*Last Name:
`
`*State:
`
`*Zip Code:
`
`Office Contact Phone:
`
`Patient Information
`
`*First Name:
`
`M.I.:
`
`*Last Name:
`
`*Date of Birth (MM/DD/YYYY):
`
`*Gender:
`
`c M
`
`c F
`
`*Address:
`
`*City:
`
`*State:
`
`*Zip Code:
`
`E-mail:
`
`*DEA No.:
`
`*Phone:
`
`*Fax:
`
`*NPI No:
`
`*Primary Phone:
`
`Cell Phone:
`
`Work Phone:
`
`Caregiver Name:
`
`Relationship to Patient:
`
`
`Caregiver Phone
`(if different than above):
`
`Does Patient Have Prescription Coverage?
`
`Insurance Information
`c Yes (provide photocopy of both sides of insurance identification card with this form) c No
`
`Policy Holder’s Name:
`
`Insurance Company Name:
`
`Insurance Phone:
`
`RxBIN No.:
`
`RxID No.:
`
`RxPCN No.:
`
`Policy Holder’s Date of Birth (MM/DD/YYYY):
`
`Relationship to Patient:
`
`RxGrp No.:
`
`Patient/Caregiver: Form must be signed before enrollment can be processed.
`By signing below, I acknowledge that:
` — My doctor/prescriber has counseled me on the serious risks and safe use of XYWAV and XYREM
` — I have asked my doctor/prescriber any questions I have about XYWAV and XYREM
`
`*Patient/Caregiver Signature:
`
`*Printed Caregiver Name (if applicable):
`
` *Date:
`
`Prescriber: Form must be signed before enrollment can be processed.
`By signing below, I acknowledge that:
` — I have counseled the patient and/or caregiver about the serious risks associated with the use of XYWAV and XYREM and the safe use
`conditions as described in the XYWAV or XYREM Patient Quick Start Guide (for adult patients) or the XYWAV or XYREM Brochure
`for Pediatric Patients and their Caregivers (for pediatric patients)
` c I have provided the patient and/or caregiver with the appropriate educational material [XYWAV or XYREM Patient Quick Start
`Guide (for adult patients) and XYWAV or XYREM Brochure for Pediatric Patients and their Caregivers (for pediatric patients)
`(optional)]
`
`*Prescriber Signature:
`
` *Date:
`
`Reference ID: 4644289
`
`

`

`PRESCRIBER BROCHURE
`
`Includes important prescribing information
`for adult and pediatric patients
`
`Reference ID: 4644289
`
`

`

`Dear Prescriber,
`Welcome to the XYWAV and XYREM REMS, which was developed in collaboration with the Food and Drug
`Administration (FDA) as a Risk Evaluation and Mitigation Strategy (REMS). A REMS is a strategy to manage
`known or potential serious risks associated with a drug product and is required by the FDA to ensure that
`the benefits of the drug outweigh its risks.
`This brochure provides information about the XYWAV and XYREM REMS that includes important
`prescribing information, educational and counseling requirements, and materials necessary for program
`enrollment and prescribing XYWAV™ (calcium, magnesium, potassium, and sodium oxybates) oral solution,
`and XYREM® (sodium oxybate) oral solution, including:
`• Prescriber Enrollment Form—a one-time enrollment is required for all prescribers of XYWAV and XYREM.
`• Patient Enrollment Form—a one-time patient enrollment in the XYWAV and XYREM REMS is required for
`each new patient for whom XYWAV or XYREM will be prescribed.
`• XYWAV and XYREM Prescription Forms—required for prescribing XYWAV and XYREM. These forms
`must be used for initial prescriptions and may also be used for refills and renewals of XYWAV and XYREM
`prescriptions.
`• XYWAV and XYREM Patient Quick Start Guides—these guides answer important questions for adult
`patients about how to get XYWAV and XYREM, how to use XYWAV and XYREM properly, and how to store
`them safely. It also gives important information about the risks associated with XYWAV and XYREM.
`• XYWAV and XYREM Brochures for Pediatric Patients and their Caregivers—these guides answer important
`questions for caregivers of pediatric patients and pediatric patients about how to use XYWAV and XYREM
`properly, how to store them safely, and how to get XYWAV and XYREM. It also gives important information
`about the risks associated with XYWAV and XYREM.
`The REMS Prescriber Enrollment Form, Patient Enrollment Form, and XYWAV Prescription Form or
`XYREM Prescription Form must be completed in full and sent to the XYWAV and XYREM REMS. For your
`convenience, all these forms are available online at www.XYWAVXYREMREMS.com, and can be requested
`by calling the XYWAV and XYREM REMS toll-free at 1-866-997-3688. The Certified Pharmacy with the
`XYWAV and XYREM REMS is responsible for processing all prescriptions for XYWAV and XYREM. Continue
`reading this brochure to learn more about the XYWAV and XYREM REMS and your responsibilities as a
`prescriber of XYWAV and XYREM.
`Please review the Prescribing Information for XYWAV and XYREM.
`XYWAV and XYREM may be dispensed only to patients enrolled in the XYWAV and XYREM REMS.
`
`XYWAV and XYREM are indicated for the treatment of cataplexy or excessive daytime
`sleepiness (EDS) in patients 7 years of age and older with narcolepsy
`
`If you require any additional assistance or information, please call the XYWAV and XYREM REMS at
`1-866-997-3688 or visit www.XYWAVXYREMREMS.com.
`Sincerely,
`Jazz Pharmaceuticals
`
`2
`Reference ID: 4644289
`
`

`

`IMPORTANT SAFETY INFORMATION
`
`CONTRAINDICATIONS
`• The use of XYWAV or XYREM in combination with sedative hypnotics is contraindicated.
`• The use of XYWAV or XYREM in combination with alcohol is contraindicated.
`• XYWAV and XYREM are contraindicated in patients with succinic semialdehyde dehydrogenase deficiency.
`
`WARNINGS AND PRECAUTIONS
`CNS Depression
`• XYWAV and XYREM are CNS depressants. Concurrent use of XYWAV or XYREM with other CNS
`depressants, including but not limited to opioid analgesics; benzodiazepines; sedating antidepressants,
`antipsychotics, or anti-epileptics; general anesthetics; muscle relaxants; and/or illicit CNS depressants, may
`increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death.
` – If use of these CNS depressants in combination with XYWAV or XYREM is required, dose reduction or
`discontinuation of one or more CNS depressants (including XYWAV or XYREM) should be considered.
` – If short-term use of an opioid (e.g., post- or perioperative) is required, interruption of treatment with
`XYWAV or XYREM should be considered.
`• Patients who have sleep apnea or compromised respiratory function may be at a higher risk of developing
`respiratory depression, loss of consciousness, coma, and death with XYWAV or XYREM use.
`Healthcare providers should caution patients/caregivers against hazardous activities requiring complete
`mental alertness or motor coordination (e.g., driving) within the first 6 hours of dosing or after first initiating
`treatment until certain that XYWAV or XYREM do not affect the patient adversely.
`Abuse and Misuse
`• XYWAV and XYREM are Schedule III controlled substances.
`• The active moiety of XYWAV and XYREM is oxybate, also known as gamma-hydroxybutyrate (GHB),
`a Schedule I controlled substance. Abuse of illicit GHB, either alone or in combination with other CNS
`depressants, is associated with CNS adverse events, including seizure, respiratory depression, decreases
`in the level of consciousness, coma, and death. Illicit GHB has also been associated with drug-facilitated
`sexual assault.
`• The rapid onset of sedation, coupled with the amnestic features of XYWAV and XYREM, particularly
`when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user
`(e.g., assault victim).
`• You should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing
`them for signs of misuse or abuse of XYWAV or XYREM (e.g., increase in size or frequency of dosing; reports
`of lost, stolen, or spilled medication; drug-seeking behavior; feigned cataplexy).
`XYWAV and XYREM REMS
`• XYWAV and XYREM are to be prescribed only to patients enrolled in the XYWAV and XYREM REMS.
`XYWAV and XYREM are available only through a restricted distribution program called the XYWAV and
`XYREM REMS. Required components of the XYWAV and XYREM REMS are:
` – Healthcare providers who prescribe XYWAV or XYREM must be specially certified. To be certified,
`prescribers must complete the REMS Enrollment Forms and comply with the REMS requirements.
` – XYWAV and XYREM will be dispensed only by the central pharmacy that is specially certified.
` – XYWAV and XYREM will be