Jazz Pharmaceuticals to Showcase Research Demonstrating Treatment Benefits of Xywav® (calcium, magnesium, potassium, and sodium oxybates) Oral Solution and Epidiolex® (cannabidiol) at American Academy of Neurology Annual Meeting
Jazz Pharmaceuticals (JAZZ) has announced the presentation of seven abstracts from its neuroscience portfolio at the 77th Annual American Academy of Neurology Meeting in April 2025. Key highlights include updated results from the Phase 4 DUET trial for Xywav® oral solution, showing statistically significant improvements in patients with narcolepsy and idiopathic hypersomnia (IH).
The DUET trial demonstrated notable improvements in Epworth Sleepiness Scale scores, reduced sleep stage shifts, increased deep sleep, and reduced awakenings in adults with narcolepsy. For IH patients, improvements were observed in ESS and Idiopathic Hypersomnia Severity Scale scores.
Additionally, a novel analysis of Epidiolex® real-world treatment patterns revealed nearly 70% persistence rate at one year among new patients. The data showed that 52% of patients took dosages >15 mg/kg/day at 12 months, with those taking >20 mg/kg/day showing the lowest discontinuation rates.
Jazz Pharmaceuticals (JAZZ) ha annunciato la presentazione di sette abstract dal suo portafoglio neuroscientifico al 77° Congresso Annuale dell'Accademia Americana di Neurologia che si terrà ad aprile 2025. I punti salienti includono risultati aggiornati dal trial di Fase 4 DUET per la soluzione orale Xywav®, che mostrano miglioramenti statisticamente significativi nei pazienti con narcolessia e ipersomnia idiopatica (IH).
Il trial DUET ha dimostrato notevoli miglioramenti nei punteggi della Scala di Sonno di Epworth, riduzione dei cambiamenti di fase del sonno, aumento del sonno profondo e diminuzione dei risvegli negli adulti con narcolessia. Per i pazienti con IH, sono stati osservati miglioramenti nei punteggi della ESS e della Scala di Severità dell'Ipersomnia Idiopatica.
Inoltre, un'analisi innovativa dei modelli di trattamento reali di Epidiolex® ha rivelato un tasso di persistenza di quasi il 70% a un anno tra i nuovi pazienti. I dati hanno mostrato che il 52% dei pazienti ha assunto dosaggi >15 mg/kg/giorno a 12 mesi, con quelli che assumevano >20 mg/kg/giorno che mostrano i tassi di interruzione più bassi.
Jazz Pharmaceuticals (JAZZ) ha anunciado la presentación de siete resúmenes de su cartera de neurociencia en la 77ª Reunión Anual de la Academia Americana de Neurología en abril de 2025. Los puntos clave incluyen resultados actualizados del ensayo de Fase 4 DUET para la solución oral Xywav®, que muestran mejoras estadísticamente significativas en pacientes con narcolepsia e hipersomnia idiopática (IH).
El ensayo DUET demostró mejoras notables en los puntuaciones de la Escala de Somnolencia de Epworth, reducción de cambios en las etapas del sueño, aumento del sueño profundo y reducción de los despertares en adultos con narcolepsia. Para los pacientes con IH, se observaron mejoras en las puntuaciones de ESS y la Escala de Severidad de la Hipersomnia Idiopática.
Además, un análisis novedoso de los patrones de tratamiento en el mundo real de Epidiolex® reveló una tasa de persistencia de casi el 70% a un año entre los nuevos pacientes. Los datos mostraron que el 52% de los pacientes tomaron dosis >15 mg/kg/día a los 12 meses, con aquellos que tomaron >20 mg/kg/día mostrando las tasas de interrupción más bajas.
재즈 제약(JAZZ)은 2025년 4월에 열리는 제77회 미국 신경학회 연례 회의에서 자사의 신경과학 포트폴리오에서 7개의 초록을 발표한다고 발표했습니다. 주요 하이라이트에는 Xywav® 경구 용액에 대한 4상 DUET 시험의 업데이트된 결과가 포함됩니다, 이는 기면증 및 특발성 과다수면(IH) 환자에서 통계적으로 유의미한 개선을 보여줍니다.
DUET 시험은 기면증이 있는 성인에서 에포스 슬립니스 스케일 점수, 수면 단계 변화 감소, 깊은 수면 증가 및 각성 감소에서 주목할 만한 개선을 보여주었습니다. IH 환자에 대해서는 ESS 및 특발성 과다수면 중증도 척도 점수에서 개선이 관찰되었습니다.
또한, Epidiolex® 실제 치료 패턴에 대한 새로운 분석는 새로운 환자 중 거의 70%의 지속성 비율을 1년 동안 보여주었습니다. 데이터에 따르면 12개월 시점에서 52%의 환자가 >15 mg/kg/일의 용량을 복용했으며, >20 mg/kg/일을 복용한 환자들은 가장 낮은 중단율을 보였습니다.
Jazz Pharmaceuticals (JAZZ) a annoncé la présentation de sept résumés de son portefeuille en neurosciences lors de la 77e Réunion Annuelle de l'Académie Américaine de Neurologie en avril 2025. Les points clés incluent des résultats mis à jour de l'essai de Phase 4 DUET pour la solution orale Xywav®, montrant des améliorations statistiquement significatives chez les patients atteints de narcolepsie et d'hypersomnie idiopathique (IH).
L'essai DUET a démontré des améliorations notables dans les scores de l'Échelle de Somnolence d'Epworth, une réduction des changements de stade de sommeil, une augmentation du sommeil profond et une réduction des réveils chez les adultes atteints de narcolepsie. Pour les patients atteints d'IH, des améliorations ont été observées dans les scores de l'ESS et de l'Échelle de Sévérité de l'Hypersomnie Idiopathique.
De plus, une analyse novatrice des modèles de traitement réels d'Epidiolex® a révélé un taux de persistance de près de 70 % après un an parmi les nouveaux patients. Les données ont montré que 52 % des patients prenaient des doses >15 mg/kg/jour à 12 mois, ceux prenant >20 mg/kg/jour montrant les taux d'abandon les plus bas.
Jazz Pharmaceuticals (JAZZ) hat die Präsentation von sieben Abstracts aus seinem Neurowissenschaftsportfolio auf dem 77. jährlichen Kongress der American Academy of Neurology im April 2025 angekündigt. Wichtige Highlights sind aktualisierte Ergebnisse der Phase-4-DUET-Studie zur Xywav®-Oral-Lösung, die statistisch signifikante Verbesserungen bei Patienten mit Narkolepsie und idiopathischer Hypersomnie (IH) zeigen.
Die DUET-Studie zeigte bemerkenswerte Verbesserungen bei Epworth-Schläfrigkeitsskalenwerten, reduzierten Schlafphasenverschiebungen, erhöhtem Tiefschlaf und reduzierten Wachzeiten bei Erwachsenen mit Narkolepsie. Bei IH-Patienten wurden Verbesserungen bei den ESS- und der Idiopathischen Hypersomnie-Schweregradskala beobachtet.
Darüber hinaus ergab eine neuartige Analyse der Epidiolex®-Behandlungsmuster in der realen Welt eine Persistenzrate von fast 70 % nach einem Jahr bei neuen Patienten. Die Daten zeigten, dass 52 % der Patienten nach 12 Monaten Dosen von >15 mg/kg/Tag einnahmen, wobei diejenigen, die >20 mg/kg/Tag einnahmen, die niedrigsten Abbruchraten aufwiesen.
- Xywav demonstrated statistically significant improvements in multiple sleep metrics for narcolepsy patients
- High persistence rate (69.9%) for Epidiolex at one year indicates strong treatment adherence
- Positive dose optimization data for Epidiolex suggests improved efficacy at higher doses
- 48% of Epidiolex patients required dosage adjustments, indicating potential initial dosing challenges
Insights
Jazz Pharmaceuticals has presented compelling clinical data bolstering the effectiveness of two key revenue drivers in its neuroscience portfolio. The Phase 4 DUET trial results for Xywav demonstrate statistically significant improvements in sleep metrics among narcolepsy patients and meaningful benefits for idiopathic hypersomnia patients. This reinforces Xywav's clinical profile as the company continues transitioning patients from Xyrem to this low-sodium formulation.
The real-world Epidiolex data revealing
While not announcing new approvals or expansion opportunities, this clinical evidence strengthens Jazz's market position in two therapeutic areas where they've made substantial investments. The focus on patient-reported outcomes also aligns with payer demands for real-world effectiveness data. This scientific validation supports continued adoption and optimal usage of two products that represent significant portions of Jazz's $8.5B market valuation.
The DUET trial results provide valuable clinical validation for Xywav across multiple objective and subjective measures. The statistically significant improvements in Epworth Sleepiness Scale scores, reduced sleep stage shifts, increased deep sleep, and fewer awakenings represent meaningful clinical benefits that address core symptoms of narcolepsy. The additional improvements in cognitive function and daytime functioning target aspects of these disorders that profoundly impact patients' quality of life.
For idiopathic hypersomnia specifically, improvements in both ESS and Idiopathic Hypersomnia Severity Scale scores are noteworthy as treatment options for this condition remain The patient-reported outcomes demonstrating improvements in cognitive complaints are particularly relevant, as cognitive dysfunction represents one of the most debilitating and treatment-resistant aspects of hypersomnia disorders.
The Epidiolex real-world evidence on dose optimization offers practical clinical guidance. The persistence data showing patients on >20 mg/kg/day had the lowest discontinuation rates challenges the common practice of conservative dosing in epilepsy. This pharmacoepidemiological evidence suggesting a dose-response relationship for both efficacy and tolerability could influence prescribing patterns toward more aggressive titration protocols. The
Updated top-line results demonstrate improved outcomes in adults with narcolepsy or idiopathic hypersomnia treated with Xywav as observed in the Phase 4 DUET (Developing Understanding of Hypersomnia by Evaluating Low-Sodium Oxybate Treatment) study
Novel analysis of real-world Epidiolex treatment patterns underscore importance of dose optimization for improved patient persistence
For
Data presented at the meeting includes an updated presentation of top-line results of the open-label, single-arm, Phase 4 DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) trial, evaluating the effectiveness and safety of low-sodium oxybate, Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution, on key sleep outcomes and daytime symptoms, including excessive daytime sleepiness (EDS), in adults with narcolepsy or idiopathic hypersomnia (IH). Notably, the results from DUET demonstrated statistically significant improvements from baseline to end of treatment in Epworth Sleepiness Scale (ESS) scores, reduced sleep stage shifts, increased deep sleep and reduced number of awakenings among adults with narcolepsy treated with Xywav. In adults with IH, Xywav treatment also showed improvements in ESS and Idiopathic Hypersomnia Severity Scale scores. Further, new patient-reported data from DUET demonstrated the association of Xywav treatment with improvements in daytime symptoms and functional impacts, including cognitive complaints, among adults with narcolepsy or IH. Xywav is indicated for the treatment of EDS or cataplexy in patients 7 years of age and older with narcolepsy and for adults with idiopathic hypersomnia.
"This year's presentations at the AAN Annual Meeting reinforce our ongoing commitment to addressing debilitating neurological disorders, with limited or no treatment options including narcolepsy, idiopathic hypersomnia and epilepsy," said Sarah Akerman, MD, head of neuroscience global medical and scientific affairs of Jazz Pharmaceuticals. "We continually strive to expand our understanding, research and capabilities in neuroscience through ongoing data generation for Xywav and Epidiolex to ensure patients' lived experiences and needs are reflected holistically. By listening to our patients, their care teams and leading industry experts, we aim to better address the unmet needs of those living with these difficult-to-treat conditions and ultimately help redefine possibilities for their lives."
Highlights at the 2025 AAN Annual Meeting include:
- Two presentations showcasing updated results from the open-label, single-arm, Phase 4 DUET trial of adults with narcolepsy or IH, which evaluated the effectiveness and safety of Xywav on key sleep outcomes, daytime symptoms, and functional impacts, including cognitive complaints, work productivity, and daily activities.
- Novel analysis of real-world Epidiolex® (cannabidiol) treatment patterns from
U.S. specialty pharmacy data found the overall probability of persistence at one year was nearly70% (69.9% ) among new patients and underscores the importance of dose optimization. The analysis shows how healthcare providers optimize dosing over time, with half (52% ) of patients taking dosages >15 mg/kg/day at 12 months and those taking an average of >20 mg/kg/day having the lowest likelihood of discontinuation. This real-world data demonstrates the importance of dose optimization for long-term persistence, which could lead to improved seizure control and tolerability.
The 2025 AAN Annual Meeting abstracts are available online at index.mirasmart.com/AAN2025.
A full list of Jazz Pharmaceuticals' presentations follows below:
Presentation Title | Lead Author | Poster Number / Session Title / |
Xywav Data | ||
Self-Reported Cognitive Complaints and Work | LD | Poster #: 002 Session: P8 Sleep 2 Session Date/Time: Tuesday, April 8, |
Effectiveness and Safety of Low-Sodium | LD | Poster #: 008 Session: P10: General Neurology: New, Session Date/Time: Tuesday, April 8, 5:00 PM – 6:00 PM |
Efficacy and Safety of Low-Sodium Oxybate in | C Chepke | Poster #: 004 Session: P12 General Neurology Posters 5 Session Date/Time: Wednesday, April 9, 11:45 AM – 12:45 PM |
Epidiolex Data | ||
Dosing Patterns and Persistence on | G Pohl | Poster #: 005 Session: P12: Epilepsy/Clinical Session Date/Time: Wednesday, April 9, 11:45 AM – 12:45 PM |
Tuberous Sclerosis Complex (TSC)– | A van Eeghen | Poster #: 005 Session: P8: Epilepsy/Clinical Session Date/Time: Tuesday, April 8, 8:00 AM – 9:00 AM |
Caregiver-Reported Real-World Use of | S Thomas | Poster #: 003 Session: P1: Epilepsy/Clinical Session Date/Time: Saturday, April 5, 11:45 AM – 12:45 PM |
Nurse-Reported Outcomes of Cannabidiol | N Wrobel | Poster #: 016 Session: P2: Epilepsy/Clinical Session Date/Time: Sunday, April 6, |
About Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution
Xywav is the only low-sodium oxybate approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. The Office of Orphan Product Development (OOPD) at the FDA also published its summary of clinical superiority findings for Xywav for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy by means of greater cardiovascular safety compared to Xyrem® (sodium oxybate) oral solution. The decision of the OOPD is based on the FDA findings that Xywav provides a greatly reduced chronic sodium burden compared to Xyrem. Xywav has 131 mg of sodium at the maximum recommended nightly dose whereas other high sodium oxybates have 1640 mg at the equivalent dose. Xywav is comprised of a unique composition of cations resulting in
Xywav is also the first and only U.S. FDA-approved treatment option for idiopathic hypersomnia in adults. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of idiopathic hypersomnia in adults. Xywav is the only FDA-approved treatment studied across the multiple symptoms of idiopathic hypersomnia, such as EDS, sleep inertia (severe grogginess or confusion when waking up), long sleep duration and cognitive impairment. Xywav can be administered as a twice- or once-nightly regimen for the treatment of idiopathic hypersomnia in adults.
The exact mechanism of action of Xywav in the treatment of adults with idiopathic hypersomnia and of cataplexy and EDS in narcolepsy is unknown. It is hypothesized that the therapeutic effects of Xywav are mediated through GABAB actions during sleep at noradrenergic and dopaminergic neurons, as well as thalamocortical neurons.1 The U.S. Drug Enforcement Agency (DEA) has designated Xywav as a Schedule III medicine. The DEA defines Schedule III drugs, substances, or chemicals as drugs with a moderate to low potential for physical and psychological dependence.1,2 Because of the risks of central nervous system (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.
Important Safety Information for Xywav
WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.
Because of the risks of CNS depression and abuse and misuse, XYWAV is available only |
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 Ill 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
In Study 2, the randomized-withdrawal clinical trial in adult patients with idiopathic hypersomnia (n=154), depression and depressed mood were reported in
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
In Study 2, confusion and anxiety occurred in
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
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 ≥
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 (≥
Additional Adverse Reactions
Adverse reactions that occurred in 2-<
Adverse reactions that occurred in ≥
Discontinuation: In Study 1, 9 of 201 patients (
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 wellcontrolled 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.
About Epidiolex®/Epidyolex® (cannabidiol)
Epidiolex/Epidyolex is a prescription, plant-derived cannabis-based medicine administered as an oral solution which contains highly purified cannabidiol (CBD). Cannabidiol, the active ingredient in Epidiolex, is a cannabinoid that naturally occurs in the Cannabis sativa L. plant. The precise mechanisms by which Epidiolex exerts its anticonvulsant effect in humans are unknown. Epidiolex was approved by the
Important Safety Information & Indications
CONTRAINDICATION: HYPERSENSITIVITY
EPIDIOLEX (cannabidiol) oral solution is contraindicated in patients with a history of hypersensitivity to cannabidiol or any ingredients in the product.
WARNINGS & PRECAUTIONS
Hepatic Injury:
EPIDIOLEX can cause dose-related transaminase elevations. Concomitant use of valproate and elevated transaminase levels at baseline increase this risk. Obtain transaminase and bilirubin levels prior to starting treatment, at 1, 3, and 6 months after initiation of treatment, and periodically thereafter, or as clinically indicated. Resolution of transaminase elevations occurred with discontinuation of EPIDIOLEX, reduction of EPIDIOLEX and/or concomitant valproate, or without dose reduction. For patients with elevated transaminase levels, consider dose reduction or discontinuation of EPIDIOLEX or concomitant medications known to affect the liver (e.g., valproate or clobazam). Dose adjustment and slower dose titration is recommended in patients with moderate or severe hepatic impairment. Consider not initiating EPIDIOLEX in patients with evidence of significant liver injury. There have been postmarketing reports of cholestatic or mixed patterns of liver injury. Elevated ammonia levels were reported in some patients with transaminase elevations; most taking concomitant valproate, clobazam, or both. Consider discontinuation or dose adjustment of valproate or clobazam if ammonia is elevated.
Somnolence and Sedation:
EPIDIOLEX can cause somnolence and sedation that generally occurs early in treatment and may diminish over time; these effects occur more commonly in patients using clobazam and may be potentiated by other CNS depressants.
Suicidal Behavior and Ideation:
Antiepileptic drugs (AEDs), including EPIDIOLEX, increase the risk of suicidal thoughts or behavior. Inform patients, caregivers, and families of the risk and advise them to monitor and report any signs of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior. If these symptoms occur, consider if they are related to the AED or the underlying illness.
Withdrawal of Antiepileptic Drugs:
As with most AEDs, EPIDIOLEX should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus.
ADVERSE REACTIONS:
The most common adverse reactions in patients receiving EPIDIOLEX (≥
PREGNANCY:
EPIDIOLEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Encourage women who are taking EPIDIOLEX during pregnancy to enroll in the EPIDIOLEX Pregnancy Surveillance Program and the North American Antiepileptic Drug (NAAED) Pregnancy Registry.
DRUG INTERACTIONS:
Strong inducers of CYP3A4 and CYP2C19 may affect EPIDIOLEX exposure. EPIDIOLEX may affect exposure to CYP2C19 substrates (e.g., clobazam, diazepam, stiripentol), orally administered P-gp substrates, or other substrates (see full Prescribing Information). Consider dose reduction of orally administered everolimus, with appropriate therapeutic drug monitoring, when everolimus is combined with EPIDIOLEX. A lower starting dose of everolimus is recommended when added to EPIDIOLEX therapy. Concomitant use of EPIDIOLEX and valproate increases the incidence of liver enzyme elevations. Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and clobazam. Dosage adjustment of EPIDIOLEX or other concomitant medications may be necessary.
INDICATIONS:
EPIDIOLEX (cannabidiol) oral solution is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older.
Please read the EPIDIOLEX full Prescribing Information for additional important information here.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information.
Contacts:
Media:
Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Investors:
Jeff Macdonald
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
InvestorInfo@jazzpharma.com
References:
- Xywav (calcium, magnesium, potassium and sodium oxybates) oral solution. Prescribing Information.
Palo Alto, CA : Jazz Pharmaceuticals, Inc. 2021. - United States Drug Enforcement Agency. Drug Scheduling. https://www.dea.gov/drug-information/drug-scheduling. Accessed March 2025.
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SOURCE Jazz Pharmaceuticals plc
FAQ
What were the key findings of Jazz Pharmaceuticals' Phase 4 DUET trial for Xywav in 2025?
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When and where will JAZZ present its latest neuroscience portfolio research?
