Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurology and Therapy

Open Access 25-04-2024 | Hypersomnia | ORIGINAL RESEARCH

Dosing Optimization of Low-Sodium Oxybate in Narcolepsy and Idiopathic Hypersomnia in Adults: Consensus Recommendations

Authors: Anne Marie Morse, Richard K. Bogan, Asim Roy, Michael J. Thorpy

Published in: Neurology and Therapy

Login to get access

Abstract

Introduction

Low-sodium oxybate (LXB) is approved for treatment of narcolepsy in patients aged 7 years and older and treatment of idiopathic hypersomnia in adults. LXB contains the same active moiety with 92% less sodium than sodium oxybate (SXB). As the indication for oxybate treatment in patients with idiopathic hypersomnia is new and allows for individualized dosing optimization, guidance for beginning LXB treatment is needed. In particular, clinicians may benefit from guidance regarding treatment initiation, dosing/regimen options, potential challenges, and treatment expectations. Additionally, pharmacokinetic profiles differ slightly between both treatments, and further guidance on transitioning from SXB to LXB in patients with narcolepsy may aid clinicians.

Methods

An expert panel of five sleep specialists was convened to obtain consensus on recommendations for these topics using a modified Delphi process.

Results

Across two virtual meetings, the panel agreed on 31 recommendations with a high degree of consensus that fell into four overarching topics: (1) introducing LXB to patients; (2) initiating LXB for adult narcolepsy and idiopathic hypersomnia; (3) addressing challenges in using LXB; and (4) transitioning from SXB to LXB. The panel recommended that clinicians provide a clear overview of how LXB works for treating symptoms in narcolepsy or idiopathic hypersomnia, as appropriate for their patients, explain safety aspects, and set expectations prior to initiating LXB treatment. Strategies for initial dosing and regimen are provided. Strategies for adjusting the dose, regimen, timing, and consideration of individual factors were developed for specific instances in which patients may have trouble staying asleep or waking up, as well as guidance for addressing potential adverse events, such as nausea, dizziness, anxiety, and depression. Discussion points based on existing literature and clinical experience were included as relevant for each statement.

Conclusion

Clinicians may use this resource to guide LXB dosing optimization with patients.
Appendix
Available only for authorised users
Literature
1.
American Academy of Sleep Medicine. International classification of sleep disorders—third edition, text revision. Darien: American Academy of Sleep Medicine; 2023.
2.
3.
Trotti LM, Ong JC, Plante DT, Friederich Murray C, King R, Bliwise DL. Disease symptomatology and response to treatment in people with idiopathic hypersomnia: initial data from the Hypersomnia Foundation Registry. Sleep Med. 2020;75:343–9.PubMedPubMedCentralCrossRef
4.
5.
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881–93.PubMedPubMedCentralCrossRef
6.
Lopez R, Arnulf I, Drouot X, Lecendreux M, Dauvilliers Y. French consensus. Management of patients with hypersomnia: which strategy? Rev Neurol (Paris). 2017;173(1–2):8–18.PubMedCrossRef
7.
Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res. 2021;20:e13387.CrossRef
8.
Xyrem [summary of product characteristics]. Brussels: UCB Pharma; 2022.
9.
Xyrem® (sodium oxybate) oral solution, CIII [prescribing information]. Palo Alto: Jazz Pharmaceuticals, Inc.; 2023.
10.
Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution, CIII [prescribing information]. Palo Alto: Jazz Pharmaceuticals, Inc.; 2023.
11.
Dauvilliers Y, Bogan RK, Sonka K, Partinen M, Foldvary-Schaefer N, Thorpy MJ. Calcium, magnesium, potassium, and sodium oxybates oral solution: a lower-sodium alternative for cataplexy or excessive daytime sleepiness associated with narcolepsy. Nat Sci Sleep. 2022;14:531–43.PubMedPubMedCentralCrossRef
12.
Szarfman A, Kuchenberg T, Soreth J, Lajmanovich S. Declaring the sodium content of drug products. N Engl J Med. 1995;333(19):1291.PubMedCrossRef
13.
US Food and Drug Administration. Quantitative labeling of sodium, potassium, and phosphorus for human over-the-counter and prescription drug products. Guidance for industry. US Food and Drug Administration; 2022.
14.
US Food and Drug Administration. Clinical review for Binosto, NDA 202344. US Food and Drug Administration; 2012.
15.
Junnarkar G, Allphin C, Profant J, et al. Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia. Expert Opin Drug Discov. 2022;17(2):109–19.PubMedCrossRef
16.
Thorpy MJ, Bogan RK. Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications. Sleep Med. 2020;68:97–109.PubMedCrossRef
17.
Felmlee MA, Morse BL, Morris ME. γ-Hydroxybutyric acid: pharmacokinetics, pharmacodynamics, and toxicology. AAPS J. 2021;23(1):22.PubMedCrossRef
18.
Chen C, Jenkins J, Zomorodi K, Skowronski R. Pharmacokinetics, bioavailability, and bioequivalence of lower-sodium oxybate in healthy participants in 2 open-label, randomized, crossover studies. Clin Transl Sci. 2021;14(6):2278–87.PubMedPubMedCentralCrossRef
19.
Bogan RK, Thorpy MJ, Dauvilliers Y, et al. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. Sleep. 2021;44(3):zsaa206.PubMedCrossRef
20.
Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. Lancet Neurol. 2022;21(1):53–65.PubMedCrossRef
21.
Horsnell M, Zhang E, Cook R, et al. Understanding the patient experience with sodium oxybate therapy for narcolepsy [poster]. In: Advances in sleep and circadian science; February 17–20, 2023; Clearwater Beach.
22.
Bogan R, Thorpy MJ, Winkelman JW, Dubow J, Gudeman J, Seiden D. Randomized, crossover, open-label study of the relative bioavailability and safety of FT218, a once-nightly sodium oxybate formulation: phase 1 study in healthy volunteers. Sleep Med. 2022;100:442–7.PubMedCrossRef
23.
Lumryz™ (sodium oxybate) for extended-release oral solution, CIII [prescribing information]. Chesterfield: Avadel CNS Pharmaceuticals; 2023.
24.
Roy A, Ito D, Morris S, Candler S, Profant J, Bae C. Individualized treatment patterns for patients with narcolepsy treated with oxybate: a clinical practice perspective. Nat Sci Sleep. 2023;15:767–78.PubMedPubMedCentralCrossRef
25.
Broder MS, Gibbs SN, Yermilov I. An adaptation of the RAND/UCLA modified Delphi panel method in the time of COVID-19. J Healthc Leadersh. 2022;14:63–70.PubMedPubMedCentralCrossRef
26.
Carter LP, Pardi D, Gorsline J, Griffiths RR. Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem): differences in characteristics and misuse. Drug Alcohol Depend. 2009;104(1–2):1–10.PubMedPubMedCentralCrossRef
27.
Kamal RM, van Noorden MS, Franzek E, Dijkstra BA, Loonen AJ, De Jong CA. The neurobiological mechanisms of gamma-hydroxybutyrate dependence and withdrawal and their clinical relevance: a review. Neuropsychobiology. 2016;73(2):65–80.PubMedCrossRef
28.
29.
Strunc MJ, Black J, Lillaney P, et al. The Xyrem® (sodium oxybate) Risk Evaluation and Mitigation Strategy (REMS) program in the USA: results from 2016 to 2017. Drugs Real World Outcomes. 2021;8(1):15–28.PubMedPubMedCentralCrossRef
30.
George CF, Feldman N, Inhaber N, et al. A safety trial of sodium oxybate in patients with obstructive sleep apnea: acute effects on sleep-disordered breathing. Sleep Med. 2010;11(1):38–42.PubMedCrossRef
31.
Gottlieb DJ, Punjabi NM. Diagnosis and management of obstructive sleep apnea: a review. JAMA. 2020;323(14):1389–400.PubMedCrossRef
32.
33.
US Xyrem Multicenter Study Group. A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003;26(1):31–5.
34.
Morse AM, Dauvilliers Y, Arnulf I, et al. Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia. J Clin Sleep Med. 2023;19(10):1811–22.PubMedCrossRef
35.
Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med. 2013;14(6):488–92.PubMedCrossRef
36.
Cohen A, Mandrekar J, St Louis EK, Silber MH, Kotagal S. Comorbidities in a community sample of narcolepsy. Sleep Med. 2018;43:14–8.PubMedCrossRef
37.
38.
Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. J Sleep Res. 2010;19(4):525–34.PubMedCrossRef
39.
Ortega-Albás JJ, López-Bernabé R, García AL, Gómez JR. Suicidal ideation secondary to sodium oxybate. J Neuropsychiatry Clin Neurosci. 2010;22(3):352r.e26-e26.PubMedCrossRef
40.
Rossetti AO, Heinzer RC, Tafti M, Buclin T. Rapid occurrence of depression following addition of sodium oxybate to modafinil. Sleep Med. 2010;11(5):500–1.PubMedCrossRef
41.
Sarkanen T, Niemelä V, Landtblom AM, Partinen M. Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate. Front Neurol. 2014;5:136.PubMedPubMedCentralCrossRef
42.
Buckley PJ, Wolf CT. Psychosis in a 22-year-old woman with narcolepsy after restarting sodium oxybate. Psychosomatics. 2018;59(3):298–301.PubMedCrossRef
43.
Canellas-Dols F, Delgado C, Arango-Lopez C, Peraita-Adrados R. Narcolepsy-cataplexy and psychosis: a case study. Rev Neurol. 2017;65(2):70–4.PubMed
44.
Chien J, Ostermann G, Turkel SB. Sodium oxybate-induced psychosis and suicide attempt in an 18-year-old girl. J Child Adolesc Psychopharmacol. 2013;23(4):300–1.PubMedCrossRef
45.
46.
47.
48.
Stefani A, Högl B. Nightmare disorder and isolated sleep paralysis. Neurotherapeutics. 2021;18(1):100–6.PubMedCrossRef
49.
Thorpy MJ, Arnulf I, Foldvary-Schaefer N, et al. Efficacy and safety of lower-sodium oxybate in an open-label titration period of a phase 3 clinical study in adults with idiopathic hypersomnia. Nat Sci Sleep. 2022;14:1901–17.PubMedPubMedCentralCrossRef
50.
Bogan RK, Roth T, Schwartz J, Miloslavsky M. Time to response with sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. J Clin Sleep Med. 2015;11(4):427–32.PubMedPubMedCentralCrossRef
51.
Rassu AL, Evangelista E, Barateau L, et al. Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and their consequences in idiopathic hypersomnia. J Clin Sleep Med. 2022;18(2):617–29.PubMedPubMedCentralCrossRef
52.
53.
Ong JC, Dawson SC, Mundt JM, Moore C. Developing a cognitive behavioral therapy for hypersomnia using telehealth: a feasibility study. J Clin Sleep Med. 2020;16(12):2047–62.PubMedPubMedCentralCrossRef
54.
Bogan RK, Foldvary-Schaefer N, Skowronski R, Chen A, Thorpy MJ. Long-term safety and tolerability during a clinical trial and open-label extension of lower-sodium oxybate in participants with narcolepsy with cataplexy. CNS Drugs. 2023;37(4):323–35.PubMedPubMedCentralCrossRef
55.
Goksan B, Gunduz A, Karadeniz D, et al. Morning headache in sleep apnoea: clinical and polysomnographic evaluation and response to nasal continuous positive airway pressure. Cephalalgia. 2009;29(6):635–41.PubMedCrossRef
56.
Plazzi G, Ruoff C, Lecendreux M, et al. Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation. Lancet Child Adolesc Health. 2018;2(7):483–94.PubMedCrossRef
57.
Schinkelshoek MS, Smolders IM, Donjacour CE, et al. Decreased body mass index during treatment with sodium oxybate in narcolepsy type 1. J Sleep Res. 2019;28(3):e12684.PubMedCrossRef
58.
Husain AM, Ristanovic RK, Bogan RK. Weight loss in narcolepsy patients treated with sodium oxybate. Sleep Med. 2009;10(6):661–3.PubMedCrossRef
59.
Ponziani V, Pizza F, Zenesini C, Vignatelli L, Pession A, Plazzi G. BMI changes in pediatric type 1 narcolepsy under sodium oxybate treatment. Sleep. 2021;44(7):1–7.CrossRef
60.
Black J, Reaven NL, Funk SE, et al. Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. Sleep Med. 2017;33:13–8.PubMedCrossRef
61.
Saad R, Ben-Joseph RH, Prince P, Stack C, Bujanover S, Taylor B. Clinical presentation prior to idiopathic hypersomnia diagnosis among US adults: a retrospective, real-world claims analysis [poster 497]. Annual Meeting of the Associated Professional Sleep Societies; June 10–13, 2021.
62.
63.
Mamelak M, Black J, Montplaisir J, Ristanovic R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep. 2004;27(7):1327–34.PubMedCrossRef
64.
Lapierre O, Montplaisir J, Lamarre M, Bedard MA. The effect of gamma-hydroxybutyrate on nocturnal and diurnal sleep of normal subjects: further considerations on REM sleep-triggering mechanisms. Sleep. 1990;13(1):24–30.PubMedCrossRef
65.
Leary EB, Kirby MT, Skowronski R, Xu K, Pfister C, Macfadden W. Effectiveness and treatment optimization among participants with narcolepsy switching from sodium oxybate to lower-sodium oxybate: interim data from the SEGUE study [poster 138]. Annual Meeting of the Associated Professional Sleep Societies; June 4–8, 2022; Charlotte, NC.
66.
Bae CJ, Zee PC, Leary EB, et al. Effectiveness and tolerability in people with narcolepsy transitioning from high-sodium oxybate to low-sodium oxybate: data from the real-world TENOR study. Sleep Med. 2023;109:65–74.PubMedCrossRef
67.
Husain AM, Zee PC, Leary EB, et al. Dosing and transition characteristics in people with narcolepsy transitioning from sodium oxybate to low-sodium oxybate: data from the real-world TENOR study. Sleep Med. 2024;113:328–37.PubMedCrossRef
68.
Miller AJ, Raj SR. Pharmacotherapy for postural tachycardia syndrome. Auton Neurosci. 2018;215:28–36.PubMedCrossRef
Metadata
Title
Dosing Optimization of Low-Sodium Oxybate in Narcolepsy and Idiopathic Hypersomnia in Adults: Consensus Recommendations
Authors
Anne Marie Morse
Richard K. Bogan
Asim Roy
Michael J. Thorpy
Publication date
25-04-2024
Publisher
Springer Healthcare
Published in
Neurology and Therapy
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-024-00607-8