SUPPORT & RESOURCES

Available resources to help manage your XYWAV patients

Here you can find informative videos to watch, helpful PDFs to download, and relevant patient profiles to explore.

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REAL PATIENT STORIES EXPERT VIDEOS

A woman walking her golden retriever in a park

Hear from patients

Brooke, a XYWAV patient, shares her journey from narcolepsy diagnosis to transitioning from XYREM to XYWAV

Brooke's journey to XYWAV

Watch Brooke talk about her diagnosis and discuss transitioning from XYREM® (sodium oxybate) oral solution to XYWAV.

Compensated for her time.

Grace, a XYWAV patient, shares her journey from narcolepsy diagnosis to transitioning from XYREM to XYWAV

Grace's transition to XYWAV

Learn about Grace's journey to diagnosis and transition to XYWAV.

Compensated for her time.

Oscar, a XYWAV patient, shares his experiences with narcolepsy and his treatment journey leading up to XYWAV

Meet Oscar

Oscar discusses his long journey to getting a narcolepsy type 1 diagnosis and his concern about sodium intake.

Compensated for his time.

Brooke, a XYWAV patient, shares her journey from narcolepsy diagnosis to transitioning from XYREM to XYWAV
Brooke's journey to XYWAV
Grace, a XYWAV patient, shares her journey from narcolepsy diagnosis to transitioning from XYREM to XYWAV
Grace's transition to XYWAV
Oscar, a XYWAV patient, shares his experiences with narcolepsy and his treatment journey leading up to XYWAV
Meet Oscar

Hear from peers
 

Man in blue suit with a black, patterned tie who is smiling

Evaluating a patient's potential comorbidities

Hear a cardiologist's thoughts on how to evaluate patients' risk of comorbidities.

Compensated for their time.

Man in black suit with black and grey patterned tie who is smiling

Impact of a low‑sodium oxybate on treatment

Find out what having a low-sodium* oxybate option means for patients 7 years of age and older with cataplexy and/or EDS in narcolepsy.

Compensated for their time.

*XYWAV contains 131 mg of sodium at the maximum recommended 9-g nightly dose.1

Man in blue suit with a black, patterned tie who is smiling
Evaluating a patient's potential comorbidities
Man in black suit with black and grey patterned tie who is smiling
Impact of a low‑sodium oxybate on treatment

Starting patients on XYWAV?
JazzCares® is here to help support your patients throughout their treatment journey.

PATIENT FINANCIAL ASSISTANCE & SUPPORT
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Reference:

  1. Chen C, Jenkins J, Zomorodi K, Skowronski R. Pharmacokinetics, bioavailability, and bioequivalence of lower-sodium oxybate in healthy participants in two open-label, randomized, crossover studies. Clin Transl Sci. 2021;14(6):2278-2287.

Explore these patient profiles to identify if XYWAV may be right for your patients.

Emily, a narcolepsy Type 1 patient

Actor Portrayal

Meet Emily

Meet Emily

Diagnosed with narcolepsy type 1 and has a family history of cardiovascular disease. Satisfied with improvement in her EDS and cataplexy with high-sodium oxybate oral solution and is resistant to transitioning to XYWAV.

  • Age: 27
  • Sex: Female
  • BP: 135/80 (normal: <120/80)1
  • Total cholesterol: 205 mg/dL (good: <200)2
  • Family health history: High incidence of cardiovascular disease
  • Lifestyle: Single, socially active, sometimes travels for work

My doctor would like to switch me from high‑sodium oxybate oral solution to XYWAV. He says my current medication has a lot of sodium, but it works well for my EDS and cataplexy, so I’d rather not take something else instead.
 

Clinical History

  • Diagnosed with narcolepsy type 1 at age 16
  • Epworth Sleepiness Scale (ESS) score decreased from 20 to 17 while taking stimulants
  • Was prescribed XYREM, a high‑sodium oxybate, at age 23. Not taking other concomitant medications
  • Most recent ESS score: 12; 6 cataplexy-free days/week
  • Family history of hypertension and hypercholesterolemia; her BP has been rising over the past several years. No history of hepatic impairment

Why should Emily consider the excessive sodium content in her nightly dose of XYREM?

On her last return visit, her physician told her:

  • A 9-g nightly dose of high‑sodium oxybate adds ~1640 mg of sodium to her daily sodium intake.3 The AHA recommends an ideal daily sodium intake of no more than 1500 mg/day for most adults4
  • XYWAV has 131 mg of sodium per maximum 9-g nightly dose.5 High‑sodium oxybates have ~1640 mg of sodium in a 9-g dose—a difference of ~1509 mg every single day3,6
  • The FDA determined XYWAV is clinically superior to XYREM, a high‑sodium oxybate, due to greater cardiovascular safety because the reduction in sodium burden at recommended doses will help a substantial proportion of patients reduce the risk of developing cardiovascular disease7*

*Based on a determination of Orphan Drug Exclusivity by the FDA Office of Orphan Products Development (OOPD) between XYWAV and XYREM.7 There are no head-to-head data for XYWAV and XYREM.

the heart

Choosing XYWAV over high‑sodium oxybates is a safer option for your patients like Emily, because it will reduce CV morbidity due to the reduction in chronic sodium burden.7

A clinical trial comparing the efficacy and safety of XYWAV and XYREM has not been conducted.

Sodium Intake & XYWAV

Ashley, Diagnosed with narcolepsy type 2

Interested in learning more about a patient on stimulants who is still experiencing cataplexy and EDS?

Meet Ashley

Ashley, a narcolepsy Type 2 patient

Actor Portrayal

Meet Ashley

Meet Ashley

Diagnosed with narcolepsy type 2. Has no comorbidities, currently treated with a stimulant, and still struggling with excessive daytime sleepiness (EDS). No family history of cardiovascular or hepatic disease.

  • Age: 31
  • Sex: Female
  • BP: 120/80 (normal: <120/80)1
  • Total cholesterol: 175 mg/dL (good: <200)2
  • Lifestyle: Married, full-time mom, weekends devoted to family activities

My EDS started in grade school, and I wasn’t diagnosed until my late teens. I’ve tried different doses of different wake-promoting agents (WPAs) and stimulants but am still sleepy during the day.
 

Clinical History

  • First reported EDS at age 10; diagnosed with narcolepsy type 2 at age 19
  • Prescribed WPAs and stimulants, but still experiences EDS
  • Currently treated with a stimulant and is not taking any other medications
  • Most recent Epworth Sleepiness Scale (ESS) score: 18 (21 at diagnosis)
  • No family history of cardiovascular disease or hepatic impairment

Why should Ashley’s physician consider adding XYWAV, instead of a high‑sodium oxybate like XYREM® (sodium oxybate) oral solution, to Ashley’s treatment plan?

On her last return visit, her physician told her:

  • Her stimulant may cause a modest increase (2-4 mmHg) in blood pressure, and a study showed that people with narcolepsy are already 2.6x more likely to experience heart failure* and 2.5x more likely to experience stroke8,9*
  • XYWAV has 131 mg of sodium per maximum 9-g nightly dose.5 High‑sodium oxybates have ~1640 mg of sodium in a 9-g dose—a difference of ~1509 mg every single day3,6
  • The FDA determined XYWAV is clinically superior to XYREM, a high‑sodium oxybate, due to greater cardiovascular safety because the reduction in sodium burden at recommended doses will help a substantial proportion of patients reduce the risk of developing cardiovascular disease7†

*Odds ratios: heart failure (95% CI) 2.6 (2.3, 2.9); P‑value <0.0001; stroke (95% CI) 2.5 (2.3, 2.7); P‑value <0.0001.8
†Based on a determination of Orphan Drug Exclusivity by the FDA Office of Orphan Products Development (OOPD) between XYWAV and XYREM.7 There are no head-to-head data for XYWAV and XYREM.

Popping pills

For your patients like Ashley, who are still experiencing EDS on WPAs and stimulants, and have a higher CV risk due to narcolepsy, consider prescribing XYWAV, the first and only low-sodium‡ oxybate.5,8,10-12

‡XYWAV contains 131 mg of sodium at the maximum recommended 9-g nightly dose.5

STARTING & TITRATING XYWAV

Sarah, a narcolepsy Type 1 patient

Interested in learning more about a patient concerned with her family history of heart disease while taking XYREM, a high‑sodium oxybate?

MEET SARAH

Sarah, a narcolepsy Type 1 patient

Actor Portrayal

Meet Sarah

Meet Sarah

Diagnosed with narcolepsy type 1; satisfied with the efficacy of high‑sodium oxybate; concerned about cardiovascular health but not aware of the high sodium content in her current sodium oxybate oral solution treatment.

  • Age: 25
  • Sex: Female
  • BP: 130/90 (normal: <120/80)1
  • Total cholesterol: 160 mg/dL (good: <200)2
  • Family health history: Some incidence of coronary heart disease and hypertension
  • Lifestyle: Single; has a full-time office job; health‑conscious; would like to be able to socialize after work more often

I've been taking an oxybate treatment for about 5 years, and it's helped with my cataplexy and excessive daytime sleepiness.3 While I try my best to eat healthily and work out regularly, I'm concerned about my family history of heart disease and blood pressure.

Clinical History

  • Diagnosed with narcolepsy type 1 at age 20
  • Has been taking XYREM® (sodium oxybate) oral solution, a high‑sodium oxybate, for the past 5 years
  • Her Epworth Sleepiness Scale (ESS) score decreased from 16 to 13
  • Frequency of cataplexy attacks decreased from 23 to 7 per week
  • Some incidence of cardiovascular events in her family
  • Sarah is health-conscious but not aware of the high sodium content of her current treatment

Why should Sarah consider the excessive sodium content in her nightly dose of high‑sodium oxybate oral solution?

Sarah is concerned about her cardiovascular health considering the prevalence of heart disease in her family and is looking for ways to modify her risk for cardiovascular disease. In addition, on her last return visit, her physician told her:

  • A study showed* that people with narcolepsy are 2.6x more likely to experience heart failure† and 2.5x more likely to have a stroke8‡
  • The FDA determined XYWAV is clinically superior to XYREM, a high‑sodium oxybate, due to greater CV safety because the reduction in sodium at recommended doses will help a substantial proportion of patients reduce the risk of developing CV disease7§
  • High‑sodium oxybates, including XYREM and LUMRYZ™ (sodium oxybate) for extended‑release oral suspension, have ~1640 mg of sodium in a 9-g dose3,6
  • XYWAV has only 131 mg of sodium per maximum 9-g nightly dose—a difference of ~1509 mg every single day at the equivalent dose3,5,6
  • Since narcolepsy is a chronic disorder, Sarah will need to be on treatment the rest of her life in order to manage her cataplexy and excessive daytime sleepiness (EDS)13

*This study compared 9312 adults with narcolepsy to 46,559 similar adults without narcolepsy.

†Odds ratio (95% CI) 2.6 (2.3, 2.9); P‑value <0.0001.

‡Odds ratio (95% CI) 2.5 (2.3, 2.7); P‑value <0.0001.

§Based on a determination of Orphan Drug Exclusivity by the FDA Office of Orphan Products Development (OOPD) between XYWAV and XYREM.7 There are no head-to-head data for XYWAV and XYREM.

the heart

Choosing XYWAV over high‑sodium oxybates—including LUMRYZ— is a safer option for your patients because it will reduce CV morbidity in a substantial proportion of patients due to the reduction in chronic sodium burden.14

A clinical trial comparing the efficacy and safety of XYWAV and LUMRYZ has not been conducted.

Sodium Intake & XYWAV

Popping pills

Do you see patients in your practice like Sarah who are on a high‑sodium oxybate oral solution? Transition them to XYWAV, the first and only low-sodium oxybate for the treatment of cataplexy and/or excessive daytime sleepiness in patients ages 7 and older with narcolepsy.5,15

Transitioning to XYWAV

Tanya, a narcolepsy type 2 patient

Interested in learning more about a patient with narcolepsy type 2 considering a non‑stimulant medication?

Meet Tanya

Tanya, a narcolepsy type 2 patient

Actor Portrayal

Meet Tanya

Meet Tanya

Diagnosed with narcolepsy type 2; not satisfied with stimulant as she is still struggling with excessive daytime sleepiness (EDS); looking for a non‑stimulant medication.

  • Age: 32
  • Sex: Female
  • BP: 140/90 (normal: <120/80)1
  • Total cholesterol: 200 mg/dL (good: <200)2
  • Family health history: High incidence of hypercholesterolemia and high blood pressure
  • Lifestyle: Married with a child; part‑time nurse; busy schedule with responsibilities that vary from day to day

I'm an on-the-go mom, and work part time as a nurse. My doctor has prescribed various wake‑promoting agents for my narcolepsy, but I still get extremely tired during the day. I want to explore other options to help treat my excessive daytime sleepiness.
 

Clinical History

  • Diagnosed with narcolepsy type 2 at age 30
  • Has been taking a wake‑promoting agent (WPA) for about 1.5 years, but Epworth Sleepiness Scale (ESS) score only decreased from 18 to 16
  • Still experiences EDS, especially worsening on days when she has to wake up earlier
  • Significant incidence of hypercholesterolemia in her family leading to cardiovascular events, and her BP has been getting higher lately
  • Tanya is aware of the harmful effects of excessive sodium and is trying to keep her dietary intake low

Why choose XYWAV for patients like Tanya who are still experiencing EDS while taking stimulants?

INDIVIDUALIZED DOSING CAN HELP OPTIMIZE AND TAILOR TREATMENT FOR EACH PATIENT

Tanya's physician has the option of individualizing doses to help optimize and tailor treatment to Tanya's needs15

  • Tanya's dosage was initiated at 4.5 g per night orally, divided into 2 doses: 2.25 g taken at bedtime and 2.25 g taken 2.5 to 4 hours later
  • Her physician increased the dosage by 1.5 g per night, divided into 2 doses, for a total of 3 g per each dose
    • XYWAV may be titrated up by 1.5 g per night per week
  • Tanya's dosage was then titrated up by 1 g per night, divided into 2 doses, for a total of 3.5 g each, in order to meet her needs*
    • Titration steps can be as precise as 0.25 g to help optimize treatment for each patient
  • Some patients may achieve better responses with unequal doses at bedtime and 2.5 to 4 hours later
  • The time between the first and second doses can be individualized from 2.5 to 4 hours

*Doses higher than 9 g per night have not been studied and ordinarily should not be administered.

Why should Tanya's physician consider adding XYWAV, instead of a high‑sodium oxybate like XYREM® (sodium oxybate) oral solution, to Tanya's treatment plan?

  • The FDA determined XYWAV is clinically superior to XYREM, a high‑sodium oxybate, due to greater cardiovascular (CV) safety because the reduction in sodium at recommended doses will help a substantial proportion of patients reduce the risk of developing CV disease7†
  • Since Tanya has been diagnosed with narcolepsy type 2, she is being closely monitored by her cardiologist. Furthermore, with the prevalence of hypercholesterolemia and high blood pressure in her family, her blood pressure has been rising above the normal range in the recent years

†Based on a determination of Orphan Drug Exclusivity by the FDA Office of Orphan Product Development (OOPD) between XYWAV and XYREM. There are no head-to-head data for XYWAV and XYREM.

Popping pills

Do you see patients in your practice like Tanya who have been unresponsive to WPAs and stimulants? Consider XYWAV instead of high‑sodium oxybates.

Dosing For New Starts

Emily, Diagnosed with narcolepsy type 1

Interested in learning about a patient taking XYREM, a high‑sodium oxybate?

Meet Emily

References:

  1. American Heart Association. Understanding blood pressure readings. Updated May 30, 2023. Accessed April 1, 2025. https://www.heart.org/en/health-topics/high-blood-pressure/understanding-blood-pressure-readings
  2. High cholesterol: overview. In: InformedHealth.org. Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Updated September 7, 2017. Accessed April 1, 2025. https://www.ncbi.nlm.nih.gov/books/NBK279318/
  3. XYREM® (sodium oxybate). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
  4. American Heart Association. Why should I limit sodium? Accessed April 1, 2025. https://www.heart.org/-/media/files/health-topics/answers-by-heart/why-should-i-limit-sodium.pdf?la=en 
  5. Chen C, Jenkins J, Zomorodi K, Skowronski R. Pharmacokinetics, bioavailability, and bioequivalence of lower-sodium oxybate in healthy participants in two open-label, randomized, crossover studies. Clin Transl Sci. 2021;14(6):2278-2287.
  6. LUMRYZ™ (sodium oxybate) for extended-release oral suspension. Prescribing Information. Chesterfield, MO: Avadel CNS Pharmaceuticals, LLC.
  7. US Department of Health and Human Services, US Food and Drug Administration website. Clinical superiority findings. Accessed April 1, 2025. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/Superiority-Findings-findings
  8. Black J, Reaven NL, Funk SE, et al. Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. Sleep Med. 2017;33:13-18.
  9. Dexedrine® (dextroamphetamine sulfate). Prescribing Information. Research Triangle Park, NC: GlaxoSmithKline.
  10. Ben-Joseph RH, Saad R, Black J, et al. Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study. Sleep. 2023;46(10):zsad161.
  11. Riaz M, Bhattacharjee R, Lo-Ciganic W, et al. Narcolepsy and Risk of Cardiovascular Outcomes Beyond Stimulant Use. Sleep. 2025;zsaf197.
  12. Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med. 2013;14(6):488-492.
  13. National Institute of Neurological Disorders and Stroke website. Narcolepsy. Updated January 20, 2023. Accessed April 1, 2025. https://www.ninds.nih.gov/health-information/disorders/narcolepsy
  14. Data on File (XYW-2023-030). Jazz Pharmaceuticals, Inc.
  15. XYWAV® (calcium, magnesium, potassium, and sodium oxybates). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

Downloadable Resources

A print version is also available from your Jazz Representative.

XYWAV DOSING AND TITRATION GUIDE

A comprehensive guide to starting XYWAV treatment in new patients and transitioning your appropriate XYREM® (sodium oxybate) oral solution patients.

  • PDF
  • 3 mb
 

PRESCRIBER CHECKLIST

A quick guide to prescribing XYWAV.

  • PDF
  • 1 mb
 

Resources to help patients get access to XYWAV

JazzCares® is here to help navigate the insurance process with resources, including:

Visit JazzCares

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Indications and Usage

XYWAV® (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, and for the treatment of idiopathic hypersomnia (IH) in adults.

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 and idiopathic hypersomnia 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

  • 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.

Notable requirements of the XYWAV and XYREM REMS 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 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 Study 1, the 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 Study 2, the randomized-withdrawal clinical trial in adult patients with idiopathic hypersomnia (n=154), depression and depressed mood were reported in 1% and 3%, respectively, of patients treated with XYWAV. All patients continued XYWAV treatment.

Two suicides and two attempted suicides occurred in adult clinical trials with oxybate (same active moiety as XYWAV). One patient experienced suicidal ideation and two patients reported depression in a pediatric clinical trial with oxybate. These events occurred in patients with and without previous histories of depressive disorders. 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.

Other Behavioral or Psychiatric Adverse Reactions

In Study 1, confusion and anxiety occurred in 1% and 5% of patients with narcolepsy treated with XYWAV, respectively. One patient experienced visual hallucinations and confusion after ingesting approximately 9 grams of XYWAV.

In Study 2, confusion and anxiety occurred in 3% and 16% of patients with idiopathic hypersomnia, respectively. One patient experienced visual hallucinations, which led to discontinuation of XYWAV.

Other neuropsychiatric reactions reported with oxybate (same active moiety as XYWAV) in adult or pediatric clinical trials and in the postmarketing setting include hallucinations, paranoia, psychosis, aggression, agitation, confusion and anxiety. 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 Study 1 and Study 2, parasomnias, including sleepwalking, were reported in 6% and 5% of adult patients treated with XYWAV, respectively.

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

The most common adverse reactions (occurring in ≥5% of XYWAV-treated patients in adult clinical trials in either narcolepsy or IH) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

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 nausea (20%), enuresis (19%), vomiting (18%), headache (17%), weight decreased (13%), decreased appetite (9%), dizziness (8%), and sleepwalking (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

Adverse reactions that occurred in 2-<5% 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. Adverse reactions occurring in 2-<5% of patients treated with XYWAV in the IH study include balance disorder, muscle spasms, fall, paresthesia, snoring, weight decreased, bruxism, confusional state, depressed mood, feeling drunk, and irritability.

Adverse reactions that occurred in ≥2% of patients in clinical studies with oxybate (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 Study 1, 9 of 201 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%). In Study 2, 17 of 154 (11%) patients across all study periods (excluding placebo during the DB RWP) (up to 42 weeks) reported adverse reactions that led to withdrawal from the study (anxiety, nausea, insomnia, vomiting, fatigue, feeling abnormal, fall, decreased appetite, dizziness, paresthesia, tremor, parasomnia, confusional state, hallucination visual, and irritability). The most common adverse reaction leading to discontinuation was anxiety (3.2%). In Study 1 and Study 2, 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), 7 of 104 patients reported adverse reactions that led to withdrawal from the study (hallucination, tactile; suicidal ideation; weight decreased; sleep apnea syndrome; affect lability; anger, anxiety, depression; and headache).

Drug Interactions

XYWAV is contraindicated 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 for narcolepsy or IH. 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 with narcolepsy have not been established.

Safety and effectiveness of XYWAV for the treatment of idiopathic hypersomnia in pediatric patients 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.

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. In the XYWAV clinical trial in adult idiopathic hypersomnia patients at recommended doses, six patients reported insomnia, two patients reported early insomnia, and one patient reported visual and auditory hallucinations 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.

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