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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)
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:
Informing prescribers, pharmacists, and patients of:
The risk of significant CNS and respiratory depression associated with XYREM.
The contraindication of use of XYREM with sedative hypnotics and alcohol.
The potential for abuse, misuse, and overdose associated with XYREM.
The safe use, handling, and storage of XYREM.
Ensuring that pharmacy controls exist prior to filling prescriptions for XYREM that:
Screen for concomitant use of sedative hypnotics and other potentially interacting agents.
Monitor for inappropriate prescribing, misuse, abuse, and diversion of XYREM.
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).
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.
Enroll in the REMS by completing the Prescriber Enrollment Form and
submitting it to the REMS.
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.
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.
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.
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.
Complete the Patient Counseling Checklist with the pharmacist.
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.
For all relevant staff involved in dispensing: successfully complete the
Module A Knowledge Assessment and submit it to the REMS.
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.
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 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.
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.
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.
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.
For all relevant staff involved in dispensing: successfully complete the
Module A Knowledge Assessment and submit it to the REMS.
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.
Train all pharmacists involved in dispensing on the requirements of the
REMS using Pharmacy Training Program – Module B.
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.
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 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.
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.
