Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary
Abstract Narcolepsy is associated with disrupted nighttime sleep (DNS). Sodium oxybate (SXB; Xyrem®), administered twice nightly, is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years or older with narcolepsy. Recently, low-sodium oxybate (LXB, Xywav®; for...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-09-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-023-00543-z |
| _version_ | 1797629911162159104 |
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| author | Russell Rosenberg Rogelio Braceras Wayne Macfadden Shawn Candler Jed Black Chad Ruoff |
| author_facet | Russell Rosenberg Rogelio Braceras Wayne Macfadden Shawn Candler Jed Black Chad Ruoff |
| author_sort | Russell Rosenberg |
| collection | DOAJ |
| description | Abstract Narcolepsy is associated with disrupted nighttime sleep (DNS). Sodium oxybate (SXB; Xyrem®), administered twice nightly, is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years or older with narcolepsy. Recently, low-sodium oxybate (LXB, Xywav®; for people 7 years of age and older), which contains 92% less sodium than SXB and is dosed twice nightly, and sodium oxybate for extended release (SXB-ER; Lumryz™; for adults), which contains equal sodium to SXB and is dosed once nightly, have also been approved to treat cataplexy or excessive daytime sleepiness in narcolepsy. This paper reviews the evidence regarding the overall impact of oxybate administration, and impact of different oxybate dosing regimens (once nightly, SXB-ER; twice nightly, SXB), on DNS in narcolepsy utilizing polysomnographic data from five clinical trials (three assessing SXB in adults [referred to here as SXB trials 1, 2, and 3], one assessing SXB in children [referred to as the pediatric SXB trial], and one assessing SXB-ER in adults [REST-ON]). Both once-nightly and twice-nightly oxybate regimens similarly improved symptoms of DNS. Regardless of dosing regimen, people with narcolepsy treated with oxybate experience roughly 42–53 arousals and 9–38 awakenings each night, with one of these awakenings on twice-nightly oxybate being due to the second dosing requirement in studies of SXB. Additionally, for SXB, but not SXB-ER, polysomnographic data has been analyzed by half of the night, demonstrating a greater positive impact on sleep architecture in the second half of the night, which might be related to its nonlinear pharmacokinetic profile. We conclude that while once-nightly and twice-nightly oxybate dosing regimens differ in their pharmacokinetic profiles, both improve DNS in patients with narcolepsy to a similar degree. |
| first_indexed | 2024-03-11T11:00:26Z |
| format | Article |
| id | doaj.art-afed787cda9b4829b7d82d79ca02a5a9 |
| institution | Directory Open Access Journal |
| issn | 2193-8253 2193-6536 |
| language | English |
| last_indexed | 2024-03-11T11:00:26Z |
| publishDate | 2023-09-01 |
| publisher | Adis, Springer Healthcare |
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| series | Neurology and Therapy |
| spelling | doaj.art-afed787cda9b4829b7d82d79ca02a5a92023-11-12T12:34:05ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362023-09-011261805182010.1007/s40120-023-00543-zImplications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A CommentaryRussell Rosenberg0Rogelio Braceras1Wayne Macfadden2Shawn Candler3Jed Black4Chad Ruoff5NeuroTrials Research, IncJazz PharmaceuticalsJazz PharmaceuticalsJazz PharmaceuticalsCenter for Sleep Sciences and Medicine, Stanford UniversityMayo ClinicAbstract Narcolepsy is associated with disrupted nighttime sleep (DNS). Sodium oxybate (SXB; Xyrem®), administered twice nightly, is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years or older with narcolepsy. Recently, low-sodium oxybate (LXB, Xywav®; for people 7 years of age and older), which contains 92% less sodium than SXB and is dosed twice nightly, and sodium oxybate for extended release (SXB-ER; Lumryz™; for adults), which contains equal sodium to SXB and is dosed once nightly, have also been approved to treat cataplexy or excessive daytime sleepiness in narcolepsy. This paper reviews the evidence regarding the overall impact of oxybate administration, and impact of different oxybate dosing regimens (once nightly, SXB-ER; twice nightly, SXB), on DNS in narcolepsy utilizing polysomnographic data from five clinical trials (three assessing SXB in adults [referred to here as SXB trials 1, 2, and 3], one assessing SXB in children [referred to as the pediatric SXB trial], and one assessing SXB-ER in adults [REST-ON]). Both once-nightly and twice-nightly oxybate regimens similarly improved symptoms of DNS. Regardless of dosing regimen, people with narcolepsy treated with oxybate experience roughly 42–53 arousals and 9–38 awakenings each night, with one of these awakenings on twice-nightly oxybate being due to the second dosing requirement in studies of SXB. Additionally, for SXB, but not SXB-ER, polysomnographic data has been analyzed by half of the night, demonstrating a greater positive impact on sleep architecture in the second half of the night, which might be related to its nonlinear pharmacokinetic profile. We conclude that while once-nightly and twice-nightly oxybate dosing regimens differ in their pharmacokinetic profiles, both improve DNS in patients with narcolepsy to a similar degree.https://doi.org/10.1007/s40120-023-00543-zNarcolepsySodium oxybateLow-sodium oxybatePolysomnographyDisrupted nighttime sleepNocturnal |
| spellingShingle | Russell Rosenberg Rogelio Braceras Wayne Macfadden Shawn Candler Jed Black Chad Ruoff Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary Neurology and Therapy Narcolepsy Sodium oxybate Low-sodium oxybate Polysomnography Disrupted nighttime sleep Nocturnal |
| title | Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary |
| title_full | Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary |
| title_fullStr | Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary |
| title_full_unstemmed | Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary |
| title_short | Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary |
| title_sort | implications of oxybate dosing regimen for sleep sleep architecture and disrupted nighttime sleep in patients with narcolepsy a commentary |
| topic | Narcolepsy Sodium oxybate Low-sodium oxybate Polysomnography Disrupted nighttime sleep Nocturnal |
| url | https://doi.org/10.1007/s40120-023-00543-z |
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