Approved Risk Evaluation and Mitigation Strategies (REMS)

REMS that have more than one drug product but are not Shared System REMS will not display the product name and ingredient properly on this website due to database limitations. Please refer to the REMS document for the correct product names.

Xywav and Xyrem (calcium, magnesium, potassium, and sodium oxybates)

NDA #021196 NDA #212690

REMS last update: 11/18/2024

• View Xywav and Xyrem's Regulatory Information at Drugs@FDA
• View Xywav and Xyrem's Regulatory Information at Drugs@FDA

• Goals
• Summary
• REMS Materials
• Assessment Plan
• Update history

What is the purpose of the REMS?

The goal of the XYREM REMS is to mitigate the risks of serious adverse outcomes resulting from inappropriate prescribing, misuse, abuse, and diversion of XYREM by:

1. Informing prescribers, pharmacists, and patients of:
1. The risk of significant CNS and respiratory depression associated with XYREM.
2. The contraindication of use of XYREM with sedative hypnotics and alcohol.
3. The potential for abuse, misuse, and overdose associated with XYREM.
4. The safe use, handling, and storage of XYREM.
2. Ensuring that pharmacy controls exist prior to filling prescriptions for 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 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

Healthcare providers who prescribe XYWAV and XYREM must:

To become certified to prescribe	Review the 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. | Prescriber Enrollment Form |
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. Document and submit to the REMS using the product-specific Prescription Form. 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 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. | XYREM Brochure for Pediatric Patients and their Caregivers | | XYREM Patient Quick Start Guide | | XYWAV Brochure for Pediatric Patients and their Caregivers | | XYWAV Patient Quick Start Guide | Enroll the patient by completing and submitting the Patient Enrollment Form to the REMS. Order the prescription using either the XYWAV Prescription Form or XYREM Prescription Form and submit it to the REMS. | XYREM Prescription Form | | XYWAV Prescription Form |
Before treatment re-initiation	For patients dis-enrolled for suspicion of abuse, misuse or diversion: Communicate with the pharmacy regarding all relevant patient history and re-enroll the patient if the prescriber and pharmacist agree. 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.
During treatment; within the first 3 months of starting treatment 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, and death, and any cases of suspected abuse, misuse, or diversion to Jazz Pharmaceuticals. Assess the patient’s potential for abuse, misuse, and diversion. Report all instances of behavior that give rise to a reasonable suspicion of abuse, misuse, or diversion, including all requests for early refills, and all reports of lost, stolen, destroyed, or spilled drug to the REMS. Report requests to disenroll a patient for suspected abuse, misuse, or diversion to the REMS.

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. | XYREM Brochure for Pediatric Patients and their Caregivers | | XYREM Patient Quick Start Guide | | XYWAV Brochure for Pediatric Patients and their Caregivers | | XYWAV Patient Quick Start Guide | 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 by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS. | Patient Enrollment Form | 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.
During treatment; within the first 3 months of starting treatment and recommended every 3 months thereafter	Be monitored by your prescriber 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 reinitiation, after lapse in treatment for 6 months or longer	Complete the Patient Counseling Checklist with the pharmacist.
At all times	Inform your prescriber and the pharmacy about any new medications you may be taking or medical conditions you may have.

The pharmacy that dispenses XYWAV and XYREM must:

To become certified to dispense	For all relevant staff involved in dispensing: review the Pharmacy Training Program – Module A. | Certified Pharmacy Training Program | For all relevant staff involved in dispensing: successfully complete the Module A Knowledge Assessment and submit it to the REMS. | Module A Knowledge Assessment | For all pharmacists involved in dispensing: review the Pharmacy Training Program – Module A and B. | Certified Pharmacy Training Program | For all pharmacists involved in dispensing: successfully complete the Module A Knowledge Assessment and Module B Knowledge Assessment and submit it to the REMS. | Module A Knowledge Assessment | | Module B Knowledge Assessment | Train all pharmacists involved in dispensing per the requirements of the Pharmacy Training Program – Module B. | Certified Pharmacy Training Program | 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 verify and document the patient has no other active prescriptions for oxybate products that overlap with the current prescription for XYWAV and XYREM by reviewing the following information received from other REMS for oxybate products: oxybate prescription information of prescriptions in process; oxybate prescription information of dispensed prescriptions that includes last dispense date, days’ supply, and prescriber’s name; and the patient and prescriber have not been disenrolled from any of the REMS for oxybate products for suspected abuse, misuse, or diversion. Establish processes and procedures to assess the patient’s potential for abuse, misuse, and diversion by reviewing the alerts and Risk Management Report histories in the REMS. | Risk Management Report | Establish processes and procedures to provide 24-7 toll-free access to a XYWAV and XYREM REMS pharmacist; to dispense no more than a onemonth 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. Establish processes and procedures to reconcile XYWAV and XYREM inventory using the pharmacy’s inventory management system.
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 using the Central Database. | Patient Counseling Checklist | For patients who report a change in their medication use or medical history: Document and submit the change to the REMS using the Central Database and the Patient Counseling Checklist (if required). 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. Verify the patient has no other active prescriptions for oxybate products that overlap with the current prescription for XYWAV or XYREM through the processes and procedures established as a requirement of the REMS by reviewing the following information received from other REMS for oxybate products: oxybate prescription information of prescriptions in process; oxybate prescription information of dispensed prescriptions that includes last dispense date, days’ supply, and prescriber’s name; and that the patient and prescriber have not been disenrolled from any other REMS for oxybate products for suspected abuse, misuse, or diversion. Document and submit to the REMS using the Central Database. Verify in the Central Database that the prescriber is certified, and the patient is enrolled in the REMS and that the patient has no other active XYWAV or XYREM prescriptions through the processes and procedures established as a requirement of the REMS. 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. Assess the patient’s and their prescriber’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 month (30 day) supply for the initial shipment. Dispense no more than a three month (90 day) 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 new patients 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. | XYREM Brochure for Pediatric Patients and their Caregivers | | XYREM Patient Quick Start Guide | | XYWAV Brochure for Pediatric Patients and their Caregivers | | XYWAV Patient Quick Start Guide |
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
To Maintain Certification to Dispense, Every Year	For all relevant staff involved in dispensing: review the Pharmacy Training Program – Module A. | Certified Pharmacy Training Program | For all relevant staff involved in dispensing: successfully complete the Module A Knowledge Assessment and submit it to the REMS. | Module A Knowledge Assessment | For all pharmacists involved in dispensing: review the Pharmacy Training Program – Modules A and B. | Certified Pharmacy Training Program | For all pharmacists involved in dispensing: successfully complete the Module A Knowledge Assessment and Module B Knowledge Assessment and submit it to the REMS. | Module A Knowledge Assessment | | Module B Knowledge Assessment | Train all pharmacists involved in dispensing on the requirements of the REMS using Pharmacy Training Program – Module B. | Certified Pharmacy Training Program |
At all times	Provide 24-7 toll-free access to a XYWAV and XYREM REMS 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. | Risk Management Report | Not distribute, transfer, loan, or sell XYWAV or XYREM. Not stock XYWAV or XYREM in retail pharmacies. Maintain records of staff training and completion of knowledge assessments. Maintain records of inventory reconciliation using the pharmacy’s inventory management system. Maintain records of all processes and procedures including compliance with those processes and procedures. 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_2024_11_18_Certified_Pharmacy_Training_Program.pdf
Module A Knowledge Assessment (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Module_A_Knowledge_Assessment.pdf
Module B Knowledge Assessment (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Module_B_Knowledge_Assessment.pdf
Patient Counseling Checklist (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Patient_Counseling_Checklist.pdf
Patient Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Patient_Enrollment_Form.pdf
Prescriber Brochure (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Prescriber_Brochure.pdf
Prescriber Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Prescriber_Enrollment_Form.pdf
REMS Document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_REMS_Document.pdf
REMS Full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_REMS_Full.pdf
REMS Website (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_REMS_Website.pdf
Risk Management Report (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Risk_Management_Report.pdf
XYREM Brochure for Pediatric Patients and their Caregivers (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_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_2024_11_18_Xyrem_Patient_Quick_Start_Guide.pdf
XYREM Prescription Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Xyrem_Prescription_Form.pdf
XYWAV Brochure for Pediatric Patients and their Caregivers (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_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_2024_11_18_Xywav_Patient_Quick_Start_Guide.pdf
XYWAV Prescription Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xywav_and_Xyrem_2024_11_18_Xywav_Prescription_Form.pdf

Assessment Plan

This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.

What updates have been made to the REMS?

Date	Summary of change
11/18/2024	Modified to remove REMS Website screenshots related to the ePrescribe Platform Healthcare Provider Registration, ePrescribe Prescription Summary, electronic prescription application and ePrescribe Platform Support Website pages; and user redirection through a new window to a website outside of the REMS website for the ePrescribe Platform Healthcare Provider Registration and ePrescribe Platform Support.
05/22/2024	Modified to make changes to the REMS Website to clarify the electronic prescribing registration process, and update the prescriber roles and responsibilities to align with the Prescriber Brochure.
03/04/2024	Revised to make editorial changes.
01/16/2024	Modified to add electronic prescribing functionality to the REMS website to allow prescribers to register for the Drug Enforcement Administration (DEA) Electronic Prescribing for Controlled Substances (EPCS) and submit Xywav or Xyrem Prescription Forms electronically through the REMS website directly to the Certified Pharmacy.
02/09/2022	Modified to make changes to the XYWAV and XYREM Prescription Forms to decrease prescriber confusion when documenting the indication for use and signing the form.
12/09/2021	Modified to make changes to the dosing table structure on the Xywav Prescription Form to prevent confusion when the prescriber fills out the form.
08/12/2021	Modified to: Make changes to the REMS materials to align with the new indication of Idiopathic Hypersomnia for Xywav Make changes to the REMS assessment timetable Change the reporting interval for the Knowledge, Attitude, and Behavior Surveys from annually to every other year Make changes to the Patient Counseling Checklist to capture additional information regarding concomitant medication and alcohol use
02/11/2021	Modified to make revisions to the most common side effects in pediatric patients listed in the Patient Counseling Checklist, Prescriber Brochure, the Xyrem and Xywav Brochures for Pediatric Patients and their Caregivers, and the REMS Supporting Document to conform with a recently approved prior approval supplement. Modified to revise the REMS document, REMS supporting document, and appended REMS materials to allow for the addition of an authorized generic for Xyrem.
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.