Nature and Science of Sleep (Aug 2023)
Long-Term Treatment of Narcolepsy and Idiopathic Hypersomnia with Low-Sodium Oxybate
Abstract
Logan D Schneider,1 Anne Marie Morse,2 Michael J Strunc,3 Joyce K Lee-Iannotti,4 Richard K Bogan5 1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; 2Janet Weis Children’s Hospital, Geisinger Medical Center, Danville, PA, USA; 3The Center for Pediatric Sleep Medicine, Children’s Hospital of The King’s Daughters, Norfolk, VA, USA; 4Department of Neurology, The University of Arizona College of Medicine, Phoenix, AZ, USA; 5Department of Pulmonology, University of South Carolina School of Medicine, Columbia, SC, USACorrespondence: Logan D Schneider, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 450 Broadway St, Pavilion C 2nd Fl MC 5704, Redwood City, CA, 94063, USA, Tel +1 650 723-6601, Fax +1 650 721-3448, Email [email protected]: Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient’s life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia.Plain Language Summary: Narcolepsy and idiopathic hypersomnia are disorders that make people feel very sleepy. Low-sodium oxybate (LXB) is a medicine for these disorders. Doctors think LXB works on parts of the brain that keep people awake. LXB may quiet those brain parts down at night by reducing their electrical activity, which helps people sleep better. LXB wears off by the morning, so people can wake up normally and feel more alert the next day. LXB has less sodium (which is part of salt) than a medicine called sodium oxybate. Sodium oxybate has been used for narcolepsy for more than 20 years. LXB has several benefits. First, LXB may be healthier than medicines that contain a lot of sodium, such as a high-sodium oxybate. This is because sodium can increase blood pressure and risk of heart disease. Second, LXB can be taken twice each night for narcolepsy, or once or twice each night for idiopathic hypersomnia. This depends on a person’s lifestyle, how well the medicine is working, and side effects. Third, people taking LXB are more able to work and do other activities and have better quality of life. Finally, people taking LXB may lose weight. This can help overweight or obese people.Keywords: cardiovascular, dosing, LXB, hypersomnolence, quality of life, weight loss
