Xyrem (sodium oxybate) Information

Drug Information

Xyrem (sodium oxybate) Oral Solution is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) with an orphan disease designation to treat cataplexy (a condition where patients suddenly lose muscle tone, including voluntary muscle control, while awake) and excessive daytime sleepiness in patients with narcolepsy.

Associated Risks and Risk Evaluation and Mitigation Strategy (REMS)

Risks associated with sodium oxybate (Xyrem) at recommended doses can include central nervous system (CNS) depression, respiratory depression, confusion, and neuropsychiatric events (such as depression). Because of the risk of CNS depression, and abuse and misuse, sodium oxybate (Xyrem) is only available through risk evaluation mitigation strategy (REMS) programs.

Xyrem is subject to a REMS with elements to assure safe use (ETASU) to mitigate the risks of serious adverse outcomes resulting from inappropriate prescribing, misuse, abuse, and diversion of Xyrem. ETASU are required medical interventions or other actions healthcare professionals need to execute prior to prescribing or dispensing the drug to the patient. Some actions may also be required for the patient to continue on treatment.

The prescription drug Xyrem is the sodium salt of gamma-hydroxybutyrate (GHB). GHB has not been approved for any medical use and has the potential for abuse, such as in cases of sexual assault. GHB is a Schedule I controlled substance under the Controlled Substances Act. FDA-approved products containing sodium oxybate, including Xyrem and now the generic version of Xyrem, are controlled under Schedule III.

Recent Actions Related to Sodium Oxybate

On January 17, 2017, the FDA approved the first generic version of Xyrem (sodium oxybate).

FDA approved the generic version of Xyrem with a separate REMS, which has the same elements to assure safe use (ETASU) as the Xyrem REMS and is designed to achieve the same level of safety.

After extensive review and consideration, the FDA waived the requirement that the brand drug (Xyrem) and generic drugs utilize a single, shared system for the REMS with ETASU. The Agency has determined that the generic sodium oxybate REMS has the same ETASU as the Xyrem REMS and operationalizes those elements in a comparable manner to the approved Xyrem REMS. Specifically, both the Xyrem REMS and the generic sodium oxybate REMS require that (1) healthcare providers who prescribe the drug be specially certified; (2) the drug be dispensed only by pharmacies that are specially certified; and (3) the drug be dispensed and shipped only to patients who are enrolled in the REMS program with documentation of safe use conditions. Therefore, both REMS programs are designed so that sodium oxybate is only prescribed and dispensed by certified healthcare providers to the intended patient, and are designed to prevent the risks of serious outcomes resulting from inappropriate prescribing, misuse, abuse, and diversion of sodium oxybate. Additionally, both programs contain the requirement that Xyrem and sodium oxybate will not be stocked in retail pharmacy outlets.

How the Xyrem REMS and Generic Sodium Oxybate REMS Programs Operate

There are some differences in the operational aspects of the ETASU in the Xyrem and the generic sodium oxybate REMS. The Xyrem REMS uses a single pharmacy and a single database to verify the safe use conditions required prior to dispensing the drug. The generic sodium oxybate REMS uses multiple certified pharmacies and multiple databases that are connected via an electronic telecommunication verification mechanism known as a “switch system,” which verifies in real-time the same safe use conditions as the Xyrem REMS prior to dispensing the drug.

Specifically, the switch system in the generic sodium oxybate REMS ensures coordination among pharmacies such that a drug is dispensed only after there is verification that the following three safe use conditions are met: (1) the patient is enrolled in the REMS, meaning that, among other things, the patient has been screened by a trained prescriber and educated about the safe use of sodium oxybate; (2) the prescriber is certified in the REMS, meaning that, among other things, the prescriber has received training on the safe use of sodium oxybate and agreed to report adverse events promptly; and (3) the patient does not have another active prescription for another generic sodium oxybate.

In addition to verifying this safety information from its own databases, the generic sodium oxybate REMS will require the certified pharmacy to contact the Xyrem REMS program to verify that the patient has no other active prescriptions for Xyrem that overlap with the prescription to be filled, and to identify any patient and prescriber dis-enrollments from the Xyrem REMS for suspected abuse, misuse or diversion. A certified pharmacy in the generic sodium oxybate REMS also will provide corresponding information (prescription information and enrollment status) to the Xyrem REMS program, so that the Xyrem REMS certified pharmacy can include that information in its central database and verify prescriptions and enrollment status against the generic sodium oxybate REMS system.

Once all checks are completed, generic sodium oxybate is shipped directly to the patient just as it is under the Xyrem REMS program. Neither Xyrem nor generic sodium oxybate will be stocked or dispensed by a retail pharmacy.

The FDA has concluded that the generic sodium oxybate REMS is comparable to, and is designed to achieve the same level of safety as, the Xyrem REMS.

The Xyrem REMS and generic REMS programs have the following same safety-related requirements.

REMS Requirement

Met by Xyrem REMS

Met by Generic REMS

Prescriber Certification: healthcare providers who prescribe sodium oxybate are required to screen, counsel, evaluate and enroll patients as well as report adverse events.

yes

yes 

Pharmacy Certification: Any pharmacy that dispenses sodium oxybate must be certified in the REMS program.

yes

yes

1.  Drug cannot be stocked in retail pharmacies (specialty, mail-order only).

yes

yes

2.  Dispense only to patients that are enrolled in the REMS

yes

yes

3.  Ensure that all pharmacy staff involved in the program are trained

yes

yes

4.  Ensure that pharmacists involved in the program are trained

yes

yes

5.  Utilize database(s) for tracking and documenting the relevant prescription and enrollment information

yes

yes 

6.  Provide toll-free access to a REMS program pharmacist

yes 

yes

7.  Ship the drug directly to each patient or designee and track the shipment

yes

yes

8.  Limit the first shipment to a one-month supply and subsequent shipments to no more than a three-month supply

yes 

yes

9.  Document and report all potential adverse events to the sponsor(s)

yes 

yes

10. Ensure completion of patient counseling checklist and its requirements and the documentation of information received

yes 

yes 

11.  Validate each prescription by

a. verifying that both prescriber and patient are enrolled and that the patient has no other active prescription

b. confirming all prescription information

yes

yes

 12.  Review the patient information, including concomitant or interacting agents, and reports regarding potential abuse, misuse, or diversion

yes 

yes 

 13.  Monitor, document, and report to sponsor(s) all instances of patient or prescriber behavior that give rise to a reasonable suspicion of abuse, misuse, or diversion

yes 

yes 

Documentation of Safe Use Conditions: sodium oxybate can only be shipped to patients who are enrolled in the REMS program with documentation of safe use conditions.

yes 

yes 

1.  The drug is dispensed only by a certified pharmacy, by direct shipment, to patients enrolled in the program.

yes 

yes

2.  Patients are enrolled in the program only if a prescriber completes the patient enrollment form.

yes 

yes 

3.  The drug is dispensed and shipped only to patients who have signed the prescriber-completed patient enrollment form and acknowledged that he/she has been counseled and asked any questions.

yes 

yes

4.  Patients remain in the program unless the pharmacy or prescriber determine they should be disenrolled.

yes

yes

5.  Disenrolled patients may re-enroll under certain conditions.

yes

yes

6.  Patients may change prescribers provided that the new prescriber is also enrolled in the program and that the new prescription does not overlap with another active prescription.

yes 

yes 

More information on these REMS programs is available on the REMS@FDA webpage.

To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program.

Regulatory History and Labeling from Drugs@FDA

Page Last Updated: 01/25/2017
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