Approved Risk Evaluation and Mitigation Strategies (REMS)

Xywav and Xyrem (calcium, magnesium, potassium, and sodium oxybates) Xywav and Xyrem (sodium oxybate)
NDA #021196 NDA #212690
REMS last update: 07/21/2020



What is the purpose of the REMS?

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:
    1. The risk of significant CNS and respiratory depression associated with XYWAV and XYREM.
    2. The contraindication of use of XYREM with sedative hypnotics and alcohol.
    3. The potential for abuse, misuse, and overdose associated with XYWAV and XYREM.
    4. 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:
    1. Screen for concomitant use of sedative hypnotics and other potentially interacting agents.
    2. Monitor for inappropriate prescribing, misuse, abuse, and diversion of XYWAV and XYREM.
    3. Notify prescribers when patients are receiving concomitant contraindicated medications or there are signs of potential abuse, misuse, or diversion.

What do participants need to know?

Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.

View application holder(s) REMS Website See Disclaimer page regarding links to external sites

Healthcare Providers who prescribe Xywav and Xyrem must

To become certified to prescribe
  • Review Xywav and Xyrem Prescribing Information.
  • Review the following: Prescriber Brochure
    | Prescriber Brochure |
  • Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
Before treatment initiation (first dose)
  • 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.
  • 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.
  • 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.
  • Enroll the patient by completing and submitting the Patient Enrollment Form to the REMS Program.
  • Order the prescription using either the XYWAV Prescription Form or XYREM Prescription Form and submit it to the REMS Program.
Before treatment re-initiation
  • 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.
  • 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.
During treatment; within the first 3 months and recommended every 3 months thereafter
  • 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.
At all times
  • Report all potential serious adverse events, including CNS depression, respiratory depression, loss of consciousness, coma, death, and any cases of abuse, misuse, or diversion to the REMS Program

Patients who are prescribed Xywav and Xyrem

Before treatment initiation
  • 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.
  • 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.
  • Enroll in the REMS Program by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program.
  • Complete the Patient Counseling Checklist with the pharmacist.
    | Patient Counseling Checklist |
During treatment
  • 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.
  • Complete the Patient Counseling Checklist with the pharmacist based on changes in your medication and/or medical history.
    | Patient Counseling Checklist |
During treatment;within the first 3 months of starting treatment and recommended every 3 months thereafter
  • 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
  • Inform your prescriber and the pharmacy about any new medications you may be taking or medical conditions you may have.

Pharmacies that dispense Xywav and Xyrem must:

To become certified to dispense
  • 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 threemonth 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.
Before dispensing
  • 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.
    | Patient Counseling Checklist |
  • 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.
  • Assess the patient’s potential for abuse, misuse, and diversion by reviewing the alerts and Risk Management Report history in the Central Database.
  • For patients who request an early refill or if abuse, misuse or diversion is suspected: Discuss the request or concern with the prescriber.
  • Dispense no more than a one months’ supply for the initial shipment.
  • Dispense no more than a three months’ supply for subsequent shipments.
Before shipping
  • Verify the patient’s shipping address and that the patient or patientauthorized adult designee will be available to receive the shipment through the processes and procedures established as a requirement of the REMS.
  • 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.
After shipping
  • Track and verify receipt of each shipment of XYWAV and XYREM through the processes and procedures established as a requirement of the REMS.
  • Document and submit the shipment and receipt dates to the Central Database.
To Maintain Certification to Dispense, Every Year
  • 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.
  • Train all pharmacists involved in dispensing on the requirements of the REMS Program using Pharmacy Training Program – Module B.
At all times
  • 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.
    | 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.
  • Not distribute, transfer, loan, or sell XYWAV or XYREM.
  • Not stock XYWAV or XYREM in retail pharmacies.
  • 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.

View additional drug-specific postmarket safety information from the FDA

What materials are included in the REMS?

The REMS includes a REMS Document. In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Xywav and Xyrem REMS, see the DailyMed link(s).
Material Name Material Name Link
Certified Pharmacy Training Program (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Certified_Pharmacy_Training_Program.pdf
Module A Knowledge Assessment (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Module_A_Knowledge_Assessment.pdf
Module B Knowledge Assessment (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Module_B_Knowledge_Assessment.pdf
Paitent Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Patient_Enrollment_Form.pdf
Patient Counseling Checklist (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Patient_Counseling_Checklist.pdf
Prescriber Brochure (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Prescriber_Brochure.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Prescriber_Enrollment_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav and Xyrem_2020_07_21_REMS_Full.pdf
REMS Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_REMS_Website_Screenshots.pdf
Risk Management Report (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Risk_Management_Report.pdf
XWAV Prescription Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Xywav_Prescription_Form.pdf
XYREM Brochure for Pediatric Patients and their Caregivers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Xyrem_ Brochure_for_Pediatric_Patients_and_ their_Caregivers.pdf
XYREM Patient Quick Start Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and Xyrem_2020_07_21_Xyrem_Patient_Quick_Start_Guide.pdf
XYREM Prescription Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Xyrem_Prescription_Form.pdf
XYWAV Brochure for Pediatric Patients and their Caregivers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2020_07_21_Xywav_ Brochure_for_Pediatric_Patients_and_ their_Caregivers.pdf
XYWAV Patient Quick Start Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and Xyrem_2020_07_21_Xywav_Patient_Quick_Start_Guide.pdf

What updates have been made to the REMS?

Date Summary of change
07/21/2020 Modified to make changes to the REMS document, add an additional NDA number to include Xywav (NDA 212690),change the name of the REMS to the ‘Xywav and Xyrem REMS’, update the REMS Document to include Xywav.In addition, this REMS modification updates the format and content of the REMS Document consistent with the October 2017 Draft Guidance. Changes to the REMS materials to add an additional NDA to include Xywav (NDA 212690),addition of the following new REMS materials: Xywav REMS Prescription Form, Xywav REMS Patient Quick Start Guide, and Xywav REMS Brochure for Pediatric Patients and Their Caregivers.
10/26/2018 Modified to update the REMS document and materials to align with labeling changes related to the new pediatric indication.
07/15/2015 Modified to change the name of the REMS from the “Xyrem Success Program” to “Xyrem REMS Program” in the Medication Guide.
02/27/2015 Approval of the REMS.

Disclaimer: This webpage provides general information about REMS programs to various REMS participants (e.g., patients, pharmacies, and healthcare providers). The summary information provided herein is not comprehensive and may not include all of the information relevant to REMS participants. This webpage does not constitute a replacement, modification, or revision of the approved REMS document, including any appended REMS materials. Refer to the approved REMS document for complete information on the REMS requirements for each approved application.

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