Skip Important Safety Information Skip Main Links
PRESCRIBING XYWAV

Learn how to get your patients started on XYWAV

All prescribers must be enrolled in the XYWAV and XYREM REMS to prescribe XYWAV. Those currently enrolled in the XYREM REMS are not required to re-enroll.

Start by enrolling your patients in the XYWAV and XYREM REMS

Like XYREM® (sodium oxybate) oral solution, XYWAV will be dispensed and shipped only to patients who are enrolled in the XYWAV and XYREM REMS with documentation of safe use.1-3

  • Prescribers should refer to the XYWAV and XYREM Prescriber Brochure for details about the prescribing process. To learn more about enrolling your patients and getting started, download the brochure at XYWAVXYREMREMS.com

Your patients taking XYREM are already enrolled in the XYWAV and XYREM REMS and will not need to re-enroll

Learn about transitioning appropriate XYREM patients to XYWAV

 

  • If you prescribe XYREM and are already enrolled, you will not need to re-enroll

Follow these steps for your patients who are not currently taking XYREM

Complete the XYWAV Prescription Form and have the patient sign the XYWAV and XYREM Patient Enrollment Form2

By signing the XYWAV Prescription Form, the prescriber…

ACKNOWLEDGES THAT HE OR SHE2:

  • Has read and understands the XYWAV full Prescribing Information (PI) and the XYWAV and XYREM Prescriber Brochure
  • Understands the approved indications, risks, and safe use conditions of XYWAV

ATTESTS THAT2:

  • XYWAV is medically appropriate for the patient
  • He or she has screened the patient for certain medical conditions and certain concomitant medications. For more information, visit XYWAVXYREMREMS.com
  • He or she has counseled the patient on the serious risks and safe use conditions of XYWAV and the preparation and dosing instructions for XYWAV. For more information, visit XYWAVXYREMREMS.com

Submit the completed and signed front page of the XYWAV Prescription Form to the Certified Pharmacy by either:

Keep the following additional information in mind

  • All required fields must be completed clearly and accurately for timely fulfillment of the patient’s prescription. Required fields are indicated by an asterisk (*)
  • Personal prescription blanks will not be accepted
  • The patient’s first shipment of XYWAV will be limited to a 1-month (30-day) supply, and refill shipments cannot exceed a 3-month (90-day) supply2
  • Each Prescription Form is valid for 6 months from the date written (initial fill plus 5 refills per prescription)2

To refill or renew a XYWAV prescription, you can:

  • Call the Certified Pharmacy at 1-866-997-3688
  • Fax the completed XYWAV Prescription Form to 1-866-470-1744
  • Submit the refill or renewal electronically
  • Mail the completed XYWAV Prescription Form to XYWAV and XYREM REMS, PO Box 66589, St. Louis, MO 63166-6589

The XYWAV Prescription Form is used for initial prescriptions and for patients who are reinitiating treatment after a lapse in therapy of 6 months or longer.

The XYWAV Prescription Form can also be used for refills and renewals.

References:

  1. XYWAVTM (calcium, magnesium, potassium, and sodium oxybates). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
  2. XYWAV and XYREM REMS Document. NDA 21196; NDA 212690. XYWAVTM (calcium, magnesium, potassium, and sodium oxybates) and XYREM® (sodium oxybate). Palo Alto, CA: Jazz Pharmaceuticals, Inc. Approved 02/2015. https://www.accessdata.fda.gov/Scripts/Cder/Rems/Index.cfm?event=IndvRemsDetails.page&REMS=345. Accessed September 15, 2020.
  3. XYREM® (sodium oxybate). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

INDICATIONS AND USAGE

XYWAVTM (calcium, magnesium, potassium, and sodium oxybates) oral solution, 0.5 g/mL total salts (equivalent to 0.413 g/mL of oxybate) is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Important Safety Information

WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.

  • Central Nervous System Depression

XYWAV is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with XYWAV at recommended doses. Many patients who received XYWAV during clinical trials in narcolepsy were receiving CNS stimulants.

  • Abuse and Misuse

The active moiety of XYWAV is oxybate or gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.

Because of the risks of CNS depression and abuse and misuse, XYWAV is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xywav and Xyrem REMS.

 

Contraindications

XYWAV is contraindicated

  • in combination with sedative hypnotics or alcohol and
  • in patients with succinic semialdehyde dehydrogenase deficiency.

 

Warnings and Precautions

Central Nervous System Depression

The concurrent use of XYWAV with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, 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 is required, dose reduction or discontinuation of one or more CNS depressants (including XYWAV) should be considered. In addition, if short-term use of an opioid (eg, post- or perioperative) is required, interruption of treatment with XYWAV should be considered.

 

After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter.

 

Abuse and Misuse

XYWAV is a Schedule III controlled substance. The active moiety of XYWAV 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 reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death. The rapid onset of sedation, coupled with the amnestic features of GHB particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (eg, assault victim). Physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely.

 

XYWAV and XYREM REMS Program

Because of the risks of central nervous system depression and abuse and misuse, XYWAV is available only through a restricted distribution program called the Xywav and Xyrem REMS Program.

Notable requirements of the Xywav and Xyrem REMS Program include the following:

  • Healthcare Providers who prescribe XYWAV are specially certified
  • XYWAV will be dispensed only by the central pharmacy that is specially certified
  • XYWAV will be dispensed and shipped only to patients who are enrolled in the XYWAV and XYREM REMS Program with documentation of safe use

Further information is available at www.XywavXyremREMS.com or 1-866-997-3688.

 

Respiratory Depression and Sleep-Disordered Breathing

XYWAV may impair respiratory drive, especially in patients with compromised respiratory function. In overdoses of oxybate and with illicit use of GHB, life-threatening respiratory depression has been reported. Increased apnea and reduced oxygenation may occur with XYWAV administration in adult and pediatric patients. A significant increase in the number of central apneas and clinically significant oxygen desaturation may occur in patients with obstructive sleep apnea treated with XYWAV. Prescribers should be aware that sleep-related breathing disorders tend to be more prevalent in obese patients, in men, in postmenopausal women not on hormone replacement therapy, and among patients with narcolepsy.

 

Depression and Suicidality

In a randomized-withdrawal clinical trial in adult patients with narcolepsy (n=201), depression and depressed mood were reported in 3% and 4%, respectively, of patients treated with XYWAV. Two patients (1%) discontinued XYWAV because of depression. In most cases, no change in XYWAV treatment was required. In clinical trials of Xyrem (same active moiety as XYWAV) in adult patients with narcolepsy (n=781), adverse reactions of depression were reported by 7% of 781 patients treated with Xyrem, with four patients (<1%) discontinuing because of depression. In most cases, no change in Xyrem treatment was required. In clinical trials of Xyrem (same active moiety as XYWAV) in adult patients with narcolepsy (n=781), there were two suicides and two attempted suicides in patients treated with Xyrem, including three patients with a previous history of depressive psychiatric disorder. Of the two suicides, one patient used Xyrem in conjunction with other drugs. Xyrem was not involved in the second suicide.

 

In the pediatric clinical trial with Xyrem (same active moiety as XYWAV) in patients with narcolepsy (n=104), one patient experienced suicidal ideation while taking Xyrem. The emergence of depression in patients treated with XYWAV requires careful and immediate evaluation. Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV, which require careful and immediate evaluation.

 

Other Behavioral or Psychiatric Adverse Reactions

In a randomized-withdrawal clinical trial in adult patients, confusion occurred in 1% of patients treated with XYWAV and anxiety occurred in 5% of patients treated with XYWAV. One patient experienced visual hallucinations and confusion after ingesting approximately 9 grams of XYWAV. Other neuropsychiatric reactions reported in clinical trials of Xyrem (same active moiety as XYWAV) in adult patients with narcolepsy and in the postmarketing setting included hallucinations, paranoia, psychosis, aggression, and agitation.

 

In a pediatric clinical trial with Xyrem (same active moiety as XYWAV) in patients with narcolepsy, neuropsychiatric reactions, including acute psychosis, confusion, and anxiety, were reported while taking Xyrem.

 

The emergence or increase in the occurrence of behavioral or psychiatric events in patients taking XYWAV should be carefully monitored.

 

Parasomnias

Parasomnias can occur in patients taking XYWAV.

 

In a randomized-withdrawal clinical trial, parasomnias, including sleepwalking were reported in 6% of adult patients treated with XYWAV. In a clinical trial of Xyrem (same active moiety as XYWAV) in adult patients with narcolepsy, five instances of sleepwalking with potential injury or significant injury were reported. Parasomnias, including sleepwalking, have been reported in a pediatric clinical trial with sodium oxybate (same active moiety as XYWAV) and in postmarketing experience with sodium oxybate. Episodes of sleepwalking should be fully evaluated and appropriate interventions considered.

 

Most Common Adverse Reactions

In the adult clinical trial, in patients with narcolepsy, the most common adverse reactions (incidence ≥5% of XYWAV-treated patients) were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety, and vomiting.

 

In the pediatric clinical trial with Xyrem (same active moiety as XYWAV), that included pediatric patients 7 to 17 years of age with narcolepsy, the most common adverse reactions (≥5%) were enuresis (18%), nausea (17%), headache (16%), vomiting (16%), weight decreased (12%), decreased appetite (8%), and dizziness (6%). The overall adverse reaction profile of XYREM in the pediatric clinical trial was similar to that seen in the adult clinical trial program. The safety profile in pediatric patients with XYWAV is expected to be similar to that of adult patients treated with XYWAV and to that of pediatric patients treated with Xyrem.

 

Additional Adverse Reactions

Additional adverse reactions that occurred in ≥2% of adult patients treated with XYWAV in the Open-Label Titration and Stable Dose Periods of the randomized-withdrawal study in adult patients with narcolepsy with cataplexy (Study 1) were fatigue, dry mouth, depressed mood, enuresis, irritability, paresthesia, depression, tremor, somnolence, and muscle spasms.

 

Additional adverse reactions that occurred in ≥2% of patients in clinical studies with Xyrem (but not in Study 1) and which may be relevant for XYWAV, were pain, feeling drunk, pain in extremity, cataplexy, disturbance in attention, sleep paralysis, and disorientation.

 

Discontinuation: In a randomized-withdrawal clinical trial 9 of 201 adult patients (4%) reported adverse reactions that led to withdrawal from the study (anxiety, decreased appetite, depressed mood, depression, fatigue, headache, irritability, nausea, pain in extremity, parasomnia, somnolence, and vomiting). The most common adverse reaction leading to discontinuation was nausea (1.5%). The majority of adverse reactions leading to discontinuation began during the first few weeks of treatment.

 

In the pediatric clinical trial with Xyrem (same active moiety as XYWAV), 5 of 104 patients reported adverse reactions that led to withdrawal from the study (hallucination, tactile; suicidal ideation; weight decreased; sleep apnea syndrome; and affect lability).

 

Drug Interactions

XYWAV should not be used in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of XYWAV.

 

Concomitant use of sodium oxybate with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study. A similar increase in exposure is expected with concomitant use of XYWAV and divalproex sodium; therefore, an initial dose reduction of XYWAV is recommended when used concomitantly with divalproex sodium. Prescribers are advised to monitor patient response closely and adjust dose accordingly if concomitant use of XYWAV and divalproex sodium is warranted.

 

Pregnancy and Lactation

There are no adequate data on the developmental risk associated with the use of XYWAV or sodium oxybate in pregnant women. XYWAV should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. GHB is excreted in human milk after oral administration of sodium oxybate. There is insufficient information on the risk to a breastfed infant, and there is insufficient information on milk production in nursing mothers. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XYWAV and any potential adverse effects on the breastfed infant from XYWAV or from the underlying maternal condition.

 

Pediatric Use

The safety and effectiveness of XYWAV for the treatment of cataplexy or excessive daytime sleepiness in pediatric patients 7 years of age and older with narcolepsy have been established. XYWAV has not been studied in a pediatric clinical trial. Use of XYWAV in pediatric patients 7 years of age and older with narcolepsy is supported by evidence from an adequate and well-controlled study of sodium oxybate in pediatric patients 7 to 17 years of age, a study in adults showing a treatment effect of XYWAV similar to that observed with sodium oxybate, pharmacokinetic data of sodium oxybate from adult and pediatric patients, and pharmacokinetic data of XYWAV from healthy adult volunteers.

 

Safety and effectiveness of XYWAV in pediatric patients below the age of 7 years have not been established.

 

Geriatric Use

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

 

Hepatic Impairment

The starting dose of XYWAV should be reduced in patients with liver impairment.

Dosage Modification in Patients with Hepatic Impairment: The recommended starting dosage in patients with hepatic impairment is one-half of the original dosage per night, administered orally, divided into two doses.

 

Dependence and Tolerance

There have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illicit use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium. These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required. The discontinuation effects of XYWAV have not been systematically evaluated in controlled clinical trials.

 

In the clinical trial experience with XYREM in narcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time. In the XYWAV clinical trial in adult narcolepsy/cataplexy patients at recommended doses, one patient reported insomnia following abrupt discontinuation of XYWAV.

 

Tolerance to XYWAV has not been systematically studied in controlled clinical trials. There have been some case reports of symptoms of tolerance developing after illicit use at dosages far in excess of the recommended XYWAV dosage regimen.

 

Please see full Prescribing Information, including BOXED Warning.

You are now leaving

XYWAV.COM

Click “OK” to continue or ”CANCEL” to return to XYWAV.COM