Tell me about Lumryz (sodium oxybate) for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy.

Lumryz (Sodium Oxybate Extended-Release)

Lumryz is a once-nightly, extended-release formulation of sodium oxybate approved by the FDA in May 2023 for treating both cataplexy and excessive daytime sleepiness in adults with narcolepsy, offering the same therapeutic benefits as twice-nightly sodium oxybate formulations but eliminating the need to wake for a second dose. 1

Formulation and Dosing Advantages

• Lumryz contains the same amount of sodium as traditional sodium oxybate (Xyrem) but is administered as a single dose at bedtime, unlike the twice-nightly dosing required with Xyrem or Xywav 1, 2
• The once-nightly formulation eliminates chronic middle-of-night awakenings, which patients have reported as disruptive to themselves and household members, and reduces risks of missed doses or accidentally taking the second dose too early 1
• Patients switching from Xyrem to once-nightly formulations typically require no dose adjustment, with 69% maintaining the same gram-for-gram dose 3

Clinical Efficacy

• The REST-ON trial demonstrated that Lumryz significantly improved excessive daytime sleepiness (patients stayed awake longer during the day), reduced cataplexy frequency, and provided overall symptom improvement compared to placebo in patients with narcolepsy type 1 and type 2 1
• Both once-nightly (Lumryz) and twice-nightly oxybate regimens similarly improve disrupted nighttime sleep, with patients experiencing roughly 42-53 arousals and 9-38 awakenings per night regardless of formulation 2
• The American Academy of Sleep Medicine issues a STRONG recommendation for sodium oxybate versus no treatment in adults with narcolepsy, based on moderate-quality evidence from 6 RCTs and 6 observational studies showing clinically significant improvements in cataplexy, excessive daytime sleepiness, and disease severity 4, 5

Critical Safety Profile

• Lumryz carries an FDA black box warning as a CNS depressant that may cause respiratory depression, requiring extreme caution in patients with any respiratory conditions 6, 5
• It is an FDA Schedule III controlled substance (sodium salt of gamma-hydroxybutyrate/GHB) and is ONLY available through the REMS program using certified specialty pharmacies 4, 6
• Concurrent use with alcohol or other CNS depressants is absolutely contraindicated due to risk of respiratory depression, seizures, decreased consciousness, coma, and death 4

Common Adverse Effects

• Frequently reported adverse events include nausea, dizziness, nocturnal enuresis (bedwetting), headache, chest discomfort, sleep disturbances, and confusion 6, 5
• Rare but serious effects include central sleep apnea, depression, and suicidality, requiring regular monitoring 5
• Weight loss, decreased appetite, nasopharyngitis, and vomiting are also commonly reported 6

Pharmacokinetic Considerations

• Lumryz has a nonlinear pharmacokinetic profile with a mean elimination half-life of 30-60 minutes, requiring rapid absorption and elimination 2, 7
• Co-administration with divalproex sodium increases GHB exposure (AUC) by approximately 25% and causes greater impairment on attention and working memory tests than either drug alone 3
• No significant pharmacokinetic interactions occur with diclofenac, ibuprofen, protriptyline, zolpidem, modafinil, fomepizole, omeprazole, or duloxetine 3

Regulatory and Insurance Requirements

• Confirmed diagnosis of narcolepsy (type 1 or type 2) is essential for insurance coverage, along with documentation of cataplexy frequency and excessive daytime sleepiness severity (using Epworth Sleepiness Scale scores) 4
• Prior authorization typically requires evidence of symptom severity and functional impairment 4
• When coverage is denied, emphasize the STRONG recommendation from the American Academy of Sleep Medicine and provide objective measures such as weekly cataplexy attack frequency 4

Combination Therapy Approach

• If excessive daytime sleepiness remains inadequately controlled on Lumryz alone, add either pitolisant or an amphetamine per American Academy of Sleep Medicine recommendations 5
• When combining amphetamines with Lumryz, exercise extreme caution due to opposing CNS effects (amphetamines increase heart rate and blood pressure while Lumryz causes CNS depression), requiring careful dose titration and close cardiovascular monitoring 5
• Approximately 59% of patients in clinical trials continued taking a stable dose of CNS stimulant throughout treatment with sodium oxybate 3

Special Population Considerations

• For pediatric patients (ages 7 and older), sodium oxybate carries only a conditional recommendation from the American Academy of Sleep Medicine, which may affect coverage decisions differently than in adults 4, 6
• Elderly patients require careful monitoring due to potential adverse effects 6
• All narcolepsy medications, including Lumryz, may cause fetal harm based on animal data, requiring risk-benefit assessment in pregnant patients 5

Monitoring Requirements

• Regular follow-up is necessary to assess treatment efficacy using objective measures (cataplexy frequency, Epworth Sleepiness Scale scores) and to evaluate for adverse effects, particularly respiratory depression 6, 5
• Monitor for signs of misuse or abuse potential, especially in patients with substance abuse history, as Lumryz is a Schedule III controlled substance 5
• Assess for cardiovascular effects when combining with stimulants 5